Diabetes Research Institute Foundation Annual Report 2013

annual report 2013 >

ONE GOAL:ACURETo restore natural insulin production and normalize blood sugar levels without imposing other risks.

Highlights of the Year 2

Message from the Director 4

Research Review 6

The Diabetes Education and Nutrition Service at the DRI 24

Faculty and Staff 25

DRIF Chairman's Message 28

Financial Summary 30

Making Progress Possible 32

The Heritage Society 36

Boards of Directors 38

DRI Foundation Staff 40

Highlightsof the Year

Advancing Research to Patients

The FDA Phase III “registration” trial of islet transplantation by the NIH Clinical Islet Transplantation Consortium (CIT) was just completed. DRI Director Dr. Camillo Ricordi presentedthe results of this unprecedented multicenter clinical trial atthe International Cell Therapy Society (ICTS) congress in Paris,France, on April 25, 2014. While islet transplantation is alreadyapproved at other DRI Federation locations, including Canada,England and Switzerland, the DRI is confident that this trial will lead to approval and eventual reimbursement of islet transplantation for the most severe forms of type 1diabetes in the United States, as well. This could represent the first time that a biologically active cell product is approved in the U.S. by the FDA. The BLA (biologic licenseapplication) is currently in preparation, together withextensive manufacturing and clinical FDA reports by the NIHCIT Consortium Team. The comprehensive islet cell productmanufacturing master batch record has been published and is available worldwide for “open access” download athttp://www.cellr4.org/article/891.

In this multicenter trial, as in most current trials of islettransplantation, the islets are transplanted into the liver of patients with the most severe forms of type 1 diabetes.However, this transplant site is not ideal for taking the nextstep on the path to a biological cure by moving away fromgeneralized treatment with anti-rejection drugs, toward local immunomodulation and immunoprotection of thetransplanted insulin-producing cells. In this direction, DRI scientists have been investigating other sites within the body that can serve as a better home for islet cells whileeventually allowing for successful biologic replacement ofinsulin-producing cells without systemic immunosuppression of the recipients. In addition, this novel site to house the DRI BioHub mini organ would provide the insulin-producing cells with the spacing, support, oxygen andnutrients they need to survive and thrive long term, whileallowing for strategies for prevention of recurrence ofautoimmunity and/or immune rejection without the need for chronic administration of anti-rejection drugs.

One area of focus is the omentum, an apron-like lining inside the abdomen. DRI scientists have been testing theomentum as a possible location for a DRI BioHub. Encouragingpreliminary data has shown that islets in the omentum can

engraft and improve blood glucose control. This excitingresearch is now moving into clinical trials.

The Food and Drug Administration (FDA) has approved the DRI’s submission to initiate a pilot clinical study to test isletstransplanted into one of the platforms considered for a DRIBioHub – a “biodegradable scaffold.” The pilot trial, which isexpected to be underway in 2014, will compare the omentumto the liver as an optimal home for islets.

The DRI also plans to test other BioHub platforms, includinga “silicone scaffold.” Researchers are in late -stage discussionswith the FDA and awaiting approval for that pilot clinical trial, which will also utilize the omentum as a transplant site.

The DRI is also planning for clinical trials in the two additionalkey strategic areas: tolerance induction and cell supply. In the area of tolerance induction, the DRI is looking toward a pilot trial using tolerance-inducing cells to re-educate theimmune system and restore self-tolerance to eliminateautoimmunity. This strategy, when successful, will also allowfor transplantation of insulin-producing cells without anti-rejection drugs. Alternatively, it will allow for regeneration ofinsulin-producing cells from patients’ own tissues, such as the native pancreas or skin cells obtained from a minimally-invasive biopsy.

In the area of cell supply, the DRI was selected as one of thesites for future clinical trials involving transplantation of stem cell-derived insulin-producing cells.

We look forward to sharing exciting progress as the DRI’s research continues to advance.

3 [2013 annual report]

At the Diabetes Research Institute, scientists are urgently pursuing the most promising research findings that show true potential to benefitpeople living with diabetes. Nothing exemplifies that commitment morethan moving exciting discoveries out of the laboratory and into clinical

trials, which help move cutting-edge therapies ahead.

This past year DRI scientists, together with their global collaborators, took several steps to advance cell replacement initiatives, pioneering

a host of new possibilities for those with T1D.

[diabetes research institute foundation] 4

I am proud to share this report, highlighting the ongoing work at the Diabetes Research Institute and our efforts both here and abroad. This next year will bea pivotal one for cure-focused research, with several efforts coming to fruition across many areas and with significant impact in the field as a whole and forpatients with T1D.

Message from theDirector


Among these is the completion of an important Phase IIIclinical trial, sponsored by the Clinical Islet TransplantationConsortium (CIT), a multi-year, multi-center undertakingsupported by two NIH institutes – the National Institute ofDiabetes and Digestive and Kidney Diseases (NIDDK) and theNational Institute of Allergy and Infectious Diseases (NIAID).

The next steps will require centers in the United States to band together and successfully complete a biological licenseapplication so that islet transplantation can be offered on a more widespread basis in our country. This cell replacementtherapy is already available to patients in other countries, such as Switzerland and Canada, where it is an approved andreimbursable procedure through one’s health insurance.

This regulatory hurdle, while not insurmountable, is importantto the public’s understanding for the need of a worldwidecollaboration – a strategy that the DRI continues to employ in structuring its long term research plans. The complexity ofthe U.S. regulatory system and the time/cost it takes to bringcellular therapies to the bedside can often move ahead muchfaster and more efficiently in other countries.

At the DRI, we capitalize on the opportunity to more swiftlytranslate promising findings to patients through our networkof global collaborators and international partners. You’ll readabout some of the exciting results of these initiatives in thepages to follow.

Today, the DRI is gearing up for critically important clinicaltrials that will take place in 2014. Among these, is the BioHub Initiative.

About a year ago, the DRI announced the BioHub Initiative, a multidisciplinary effort to design, develop and test abioengineered “mini organ” that mimics the environment of one’s own pancreas. This groundbreaking platform would house insulin-producing cells (islets) capable of sensing blood sugar and releasing insulin as needed, in real time, and represents a major step forward in cellreplacement strategies.

As opposed to infusing islets into the liver, a BioHub allowsresearchers to select a dedicated location for the mini-organ.This provides the ability to monitor the site and cells,incorporate other cell types that would facilitate engraftment,slow or prevent rejection, and allow for its retrieval if needed.

DRI scientists have been investigating an optimal site withinthe human body that can host a BioHub, a location that wouldallow us to move toward a delivery system that will avoid theneed for long-term use of anti-rejection drugs. To that end, a new site within the abdomen will be tested this year in a Phase I/II pilot trial, as part of the BioHub Initiative, pending final regulatory approvals. This first trial will test the use of a “biodegradable scaffold” to ensure the targeted site ofimplant is a suitable place for long-term islet survival.

Also, the DRI is planning to test another BioHub platform in the coming year. We are in discussions with the FDA and are awaiting approval for that pilot trial to begin testing a “silicone scaffold” implanted in the omentum.

Other clinical trials are in our research pipeline and will beconducted with our collaborators. The DRI has been selected as a testing site for several pending patient studies.

Please join the Diabetes Research Institute and itsFoundation and be part of the team that will shape thefuture, making it one free of diabetes in our lifetime.

Warmest regards,

Camillo Ricordi, M.D.

Stacy Joy Goodman Professor of SurgeryDistinguished Professor of MedicineProfessor of Biomedical Engineering,

Microbiology & ImmunologyDirector, Diabetes Research Institute

and Cell Transplant Center University of Miami

[diabetes research institute foundation] 6[diabetes research institute foundation]6

Cases of diabetes have been documented for several thousand years, thoughthe term wasn’t coined until the first century. For almost 2,000 years sincethen, the only treatment option for patients was starvation until the discoveryof insulin in 1922.

Insulin has indeed saved the lives of millions of people with this disease. Over the lastcentury, advancements in new treatments, aided by the remarkable developments incomputer technology, have helped patients better manage daily blood glucose (sugar)control. While it is a life-saving breakthrough, insulin is not a cure and insulin treatment still cannot fully prevent the chronic complications associated with diabetes. Additionally,intensive insulin treatment has led to an increased risk of severe hypoglycemia (dangerously low blood sugar levels).

[

Research Review


Despite patients’ best attempts, diabetesmanagement remains a challenging, daily balancing act that requires constantvigilance and attention. In other words,there are no breaks because technologycannot ideally mimic the exquisite,biological function of a healthy pancreas.

Why?

Pancreatic islet cells, which make up only one to twopercent of the organ, have a built-in glucose sensor,produce their own insulin, secrete the precise amountneeded in a perfectly-timed release, and produce counter-regulatory hormones, such as glucagon, keeping bloodsugar levels in a normal range for an entire lifetime – untilthese cells are destroyed by the immune system in thosewith type 1 diabetes.

For decades, scientists across the globe have investigatedmethods to give back to patients the ability to make their own insulin. This has been the intense focus of theDiabetes Research Institute and Foundation, where thegoal is to restore natural insulin production and normalizeblood sugar levels without imposing other risks.

Years of research advancements in cell replacementtherapies have yielded promising results. The DRI and itscollaborators worldwide already have demonstrated thatnatural insulin production can be restored through islettransplantation. Patients involved in clinical trials haveachieved insulin-independence after receiving infusions of these cells; some study patients are living without the need for insulin injections for more than a decade.

Those receiving islet transplants not only have hadnormalized blood sugar levels, they have also been freed from frightening hypoglycemic episodes and have experienced a much higher quality of life.

Yet for all the benefits of islet transplantation, this therapy has been limited to only the most severe cases of diabetes due to several remaining challenges.

Through decades of experience in clinical islettransplantation, DRI researchers are armed with critical insights for overcoming these hurdles andReaching the Biological Cure.


Certain cells in the body that have beneficial properties can be added to help promote

long-term islet survival.

Co-delivery of “helper” cells

Local delivery of low-dose drugs directly into the site can

reduce inflammation and protect the islets from an immune attack.

Localized Drug Delivery

Reversing the autoimmune attack on the islet cells that caused

the onset of diabetes.

Re-educating the Immune System

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Reaching the Biological CureThe DRI BioHub – A Unique Solution

The Institute’s approach to restore natural insulinproduction is to develop a DRI BioHub, an integrated miniorgan that mimics the native pancreas, containing thecritical insulin-producing cells that naturally control bloodsugar levels. But the BioHub goes beyond traditional islettransplantation and is uniquely different from the variousapproaches underway at other research centers.

The BioHub attempts to replicate the cells’ idealenvironment, where healthy islets thrive prior to theirdestruction by the immune system. Inside the pancreas,

the insulin-producing cells have sufficient oxygen, adequate space and all the nutrients needed to performtheir demanding job of normalizing blood sugar levels.

With a BioHub, scientists can manipulate and enhance the transplant site, add vital components, like oxygen-generating materials, “helper” cells or other agents topromote the cells’ long term function. Additionally, aBioHub platform can be used to house not just islets, butany insulin-producing cell type that scientists may create.


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Encapsulation

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Vascular Infiltration

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While this approach has shown that islet replacement can work, there are concerns that only a portion of the islets may survive post-transplant. That’s because when islets are infused into the liver, the site becomesinflamed, the cells tend to clump together due to the lack of appropriate spacing, and blood flow and oxygen are reduced. Also, the cells are continuously exposed to harmful medications and other toxins that are processed in the liver.

To overcome this challenge, the DRI is exploring alternativeimplant sites and is now focused on the omentum, theinside lining of the abdomen. The omentum plays animportant role in protecting the internal organs frominfections, bleeding, trauma and inflammation. Implantingislets into the omentum is appealing because the site isrich with blood vessels throughout its large surface area.Also, it can be easily accessed surgically.

THE DRI’S TEAMS OF RESEARCHERS ARE COMBINING THEIR MULTIDISCIPLINARY EXPERTISE TO ADDRESS THREE MAJOR CHALLENGES THAT THE BIOHUB PLATFORM OVERCOMES:

AREA 1: The Site – developing an optimal environment within the body to house and protect insulin-producing cells.

AREA 2: Sustainability – retraining the immune system to prevent the rejection of donor tissue and reversing the autoimmune attack which caused the onset of diabetes.

AREA 3: Supply – identifying, developing and/or regenerating a limitless supply of cells to sense blood glucose levels and produce insulin.

Over the last year, DRI scientists have made significant progress in each of these areas toward the development of the DRI BioHub.

AREA 1 THE SITE

In traditional islet cell transplantation, the donor cells are infused into the patient’s liver. The liver has been the site of choice due to its many advantages: it is easily accessible; cells can be implanted without invasive surgery; and it’s rich in blood vessels, which can supply the cells with oxygen and nutrients.

[ For years, scientists have beentransplanting islet cells into the liver,but that site may not be an idealhome for the cells. The focus is nowon the omentum, an apron-like lininginside the abdomen.


Preliminary data has been very encouraging indemonstrating that islets in the omentum can fully engraft and improve blood glucose control in experimental and pre-clinical models.

DRI scientists are focused on two approaches using theomentum as an alternative transplant site. In the past year, significant progress has been made with each as the work moves toward pilot clinical trials.

SILICONE SCAFFOLD

The DRI’s tissue engineering team, led by Dr. Cherie Stabler,has created a sponge-like scaffold to serve as a physicalplatform for housing the transplanted islet cells. Thesescaffolds are comprised of only 10 percent silicone. The restis open space, creating tiny pores that can house thousandsof insulin-producing cells of many shapes and sizes.

While the islet-loaded scaffold has shown safety and theability to achieve insulin independence in pre-clinical studymodels, DRI researchers have been confronted with severalregulatory hurdles. When the IND (Investigational NewDrug/Device) application was submitted, the FDA classifiedthe silicone scaffold platform as a combination of both a new “Biological” and new “Device” application, and required further pre-clinical studies before approving pilot clinical trials.

While pursuing FDA approval, the DRI is speaking with itsDRI Federation collaborators outside of the United States to assess the ability to begin initial clinical testing in theircenters so that the pilot studies are not delayed.

BIODEGRADABLE SCAFFOLD

In addition to using silicone scaffolds, DRI researchers aredeveloping and testing a biodegradable scaffold to serve as a BioHub platform.

This approach uses the patient’s own plasma, the liquidpart of the blood that does not contain any cells, togetherwith thrombin, a commonly-used, clinical-grade enzyme. When combined, they create a gel-like substance that sticks to the omentum and holds the islets in place.

Researchers will then fold over part of the omentum tocreate a protective pouch around the biodegradablescaffold mixture.

Over time, the body will absorb the gel, leaving the isletsintact, while new blood vessels are formed to support theirsurvival and function.

The biodegradable scaffold will allow researchers to addvital components to optimize islet acceptance and promotetheir long-term survival and function, such as oxygenpromoters, helper cells, local drug delivery and cellsencapsulated with protective coatings.

[Dr. Cherie Stabler, director of tissue engineering, and her team developed a silicone scaffold, one of the platforms being tested for a DRI BioHub.


AREA 2 SUSTAINABILITY

The body’s immune system serves as a protector from harmful bacteria and viruses inthe environment. This is why people rarely become ill with infections despite the factthat they probably encounter infectious agents every day. Like built-in “radar,” theimmune system continually scans the body, discriminating what is “self” and what is“foreign” and needs to be eliminated.

Yet the immune system isnot perfect, and despitemany mechanisms of controland regulation, mistakes can occur. Such mistakes can result in autoimmunediseases; like “friendly fire,”the immune systemmistakenly destroys its owntissues or cells. This is thecase with type 1 diabetes(T1D) in which the insulin-

producing cells within the pancreas are mistakenlytargeted and destroyed.

The DRI already has shown that natural insulin productioncan be restored by transplanting insulin-producing isletcells into patients with type 1 diabetes. Many transplantrecipients have been able to stop taking insulin injections;some for more than 10 years.

But challenges remain, among them keeping thetransplanted islets healthy and functioning. That’s because the recipient’s immune system sees the cells as “foreign” and wants to destroy them.

To prevent the body from rejecting the cells, patients must take powerful anti-rejection drugs. They’re calledimmunosuppressants because they suppress the immune system.

But these powerful drugs, which the recipient must takelong-term, suppress a patient’s entire immune system,leaving him or her exposed to illnesses. The drugs also can cause serious side effects and can even damage thetransplanted cells.

That’s why islet transplantation has been limited to onlythe most severe cases, including people who are unawarewhen their blood sugar levels drop dangerously low (acondition called hypoglycemic unawareness).

The DRI is committed to making this therapy available to all who can benefit. DRI scientists are focusing a great deal of attention, and resources, on protectingislets and establishing immune tolerance by educating the immune system so it “tolerates” the transplantedinsulin-producing cells without the need for long-termimmunosuppressants.

With the DRI BioHub, the Institute is pursuing severalpromising strategies to sustain the long-term health and function of the insulin-producing cells by preventing their destruction by the immune system.

USING BONE MARROW-DERIVED CELLS TO ACHIEVE TOLERANCE

Scientists have shown that transplanting bone marrowfrom a donor to a recipient can help re-educate therecipient’s immune system. If a peaceful co-existence ofthe two immune systems can be maintained, then therecipient will recognize any transplanted organs, tissues orcells from the same bone marrow donor as “self” and nochronic immunosuppression will be needed. The mixtureof these two immune systems is known as chimerism.

In the past, scientists were reluctant to use this approach.That’s because they had to give recipients harsh pre-conditioning treatments prior to the bone marrowtransplant. For example, in cases of blood disease, thepatient undergoes radiation to destroy the diseased cellsand to make space for the new, healthy bone marrow cells.Researchers could not justify this risky pre-conditioningregimen in patients with type 1 diabetes who areotherwise healthy.

But now, improved technology and advances in thelaboratory have led to innovative clinical trials using bone marrow aimed at establishing immune tolerance to transplanted organs.


DRI Director Dr. Camillo Ricordi and the University ofLouisville’s Dr. Suzanne Ildstad were among the first toshow that establishing stable chimerism resulted intolerance to transplanted pancreatic insulin-producing islet cells – preventing immune destruction.

Utilizing a new process with a specialized population ofbone marrow cells, Dr. Ildstad and her team performedbone marrow transplants using the new protocol in kidneytransplant patients. Over 20 patients have been treatedwith this novel protocol that was successful in establishinghigh levels of chimerism, allowing patients to discontinuethe use of anti-rejection drugs, now for over five years.

The DRI is collaborating with Dr. Ildstad and hercolleagues to adapt this approach for the reversal of type 1 diabetes. The new processing technology, developedby Dr. Ildstad, has shown great potential to eliminate theneed for anti-rejection drugs in organ transplant recipients.

RESTORING IMMUNE SYSTEM BALANCE

When the immune system works properly, it performs adelicate balancing act. On one side: cells that are poised toattack. On the other: cells that prevent an attack. When allgoes according to plan, the first group will attack “foreign”invaders such as viruses. But the second group will preventthe first from attacking “self” – a person’s own organs and tissues.

In autoimmune diseases such as type 1 diabetes, theimmune system loses that balance and cells are able to harm the body. DRI researchers are focused on restoring that balance and are currently pursuingtwo strategies.

NATURAL KILLER CELLS – THE FIRST LINE OF DEFENSE

When something foreign enters the body, “innateimmunity” is the first line of defense. The immune systeminitiates a cascade of events that ultimately eliminates the invader. The first responders are called “Natural Killer” or “NK” cells. As the name suggests, they are the attackersof the innate immune system. As in downstream immuneresponders, the NK cells have both an “attacking” arm and a “regulatory” arm to keep the immune response fromgetting out of control.

Research shows that in people with autoimmune diseases,such as type 1 diabetes, NK cells are dysfunctional and arefewer in number, causing dysregulated immune responsesand the shift to the late immune responses and unchecked

inflammation that is characteristic of autoimmunity. The DRI’s goal is to determine what causes this imbalanceand dysregulation in the innate immune system and torestore the natural balance between those NK cells thatinitiate an immune response, and those that prevent it.

NK cells are especially important because they’re involvedso early in immune response. By focusing on NK cells,researchers are trying to stop the autoimmune process“upstream.” They believe that upstream imbalances inthe NK cell population, particularly in the regulatorysubpopulation, likely lead to the "downstream" destruction of “self” tissue in autoimmunity. Additionally, they feel thatby fixing the “upstream” problems, the downstream effectmight be the correction of the dysregulated late immuneresponse and inflammation of autoimmunity.

Drs. Luca Inverardi, Allison Bayer and Chris Fraker areinvestigating the role of regulatory NK cells in the onset of autoimmunity, using type 1 diabetes as the modelsystem. Current studies at the DRI are providing importantsignaling data involved in increasing the numbers offunctional regulatory NK cells.

Additional studies will focus on identifying NK cells duringdisease progression, how to utilize these cells as a cellulartherapy in the context of islet transplantation and their rolein cell replacement therapies.

[ Drs. Chris Fraker and Allison Bayer are investigating therole of a special population of immune cells that play akey role in autoimmunity.


BOOSTING THE NUMBER OF REGULATORY T CELLS

The effector (attacker) cells involved in the downstreamimmune response, mentioned above, identify what is“foreign” and then destroy the invaders.

But in autoimmune diseases, effector cells target apatient’s own tissues and cells. In type 1 diabetes, they attack the insulin-producing cells in the pancreas.Another group of immune cells is supposed to control effector cells and prevent autoimmunity.

These protective cells are known as Regulatory T cells, or T-regs. In many autoimmune diseases, T-regs appear to beimpaired. If researchers are able to boost their numbersand improve their function, then they may help themcontrol effector cells and avoid autoimmunity.

Over the past several years, DRI researchers have beenstudying the role of IL-2 (interleukin 2), a natural substanceand a growth factor released by certain types of immunecells. IL-2 plays a critical role in the function of botheffector cells and T-regs. High dose IL-2 has been used incancer patients as a way to stimulate the effector cells to eliminate the cancer. The DRI’s Dr. Thomas Malek’slandmark studies in experimental mice showed that IL-2 also plays a key role in maintaining proper T-regfunction – preventing autoimmunity.

This past year, Drs. Alberto Pugliese and Malek showedthat human T-regs are highly sensitive to IL-2 and respondto much lower doses compared to effector and memoryimmune cells, which need much higher levels of IL-2 toinitiate a response.

Other researchers also showed that low-dose IL-2improved T-reg function and was able to reverseautoimmune diabetes in experimental models. Theseimportant findings point to the use of IL-2 itself, at low dose, as a potential therapy for the control of

autoimmunity. By using low doses of IL-2, researchers hope to selectively boost the levels and function of T-regs without activating effector cells.

In doing so, enhanced T-reg function should controlautoimmunity with a therapy that stimulates the naturalregulatory properties of the immune system, as opposedto the conventional anti-rejection drug therapy and theirassociated harsh side effects.

Low dose IL-2 recently has been tested in clinical trials of two immune-mediated diseases, showing safety andimproved T-reg function, as well as improvements ofclinical symptoms.

Drs. Pugliese and Malek have been working with Dr. David Klatzmann at the Université Pierre et Marie Curie in Paris. He recently completed a pilot clinical trial in patients with type 1 diabetes. The studytested safety and compared various low doses of IL-2 tobegin to determine the optimal dose and the potentialeffects on diabetes and T-reg function.

The researchers are encouraged by the preliminary resultsand enthusiastic about the potential of low dose IL-2therapy to stimulate regulation and restore the immunesystem’s balance in type 1 diabetes. The use of a naturalsubstance should be much safer than conventional anti-rejection drug therapy and their associated harsh side effects.

Success will enable researchers to intervene and preventdiabetes in individuals at the time of diagnosis, while they still have some functioning insulin-producing cells,and pre-empt the onset of diabetes in those who areknown to be at high risk for developing the disease. Thistherapy may also be applicable to patients undergoing an islet transplant (or any other insulin-producing cellreplacement therapies under development), as a means of ensuring that the autoimmune disease

[ In an effort to restore immune system balance, Drs. Alberto Pugliese (left) and Thomas Malek have shown that the use of low doses of IL-2 iseffective in increasing the number of Regulatory T cells, which play a critical role in autoimmunediseases, like T1D.


that caused type 1 diabetes in the first place doesn’tattack the new cells.

Dr. George Burke, a University of Miami transplant surgeon, and Dr. Pugliese have identified pancreastransplant recipients, who, over time, had a recurrence of autoimmunity. The insulin-producing cells in thetransplanted pancreas are targeted for destruction which,again, results in type 1 diabetes. The researchers plan to test low dose IL-2 in these patients to see if this approachcan stop the process and save the cells.

LEARNING FROM CANCER

Scientists have been studying how some tumors haveevolved in such a manner that they can escape from theimmune system so that they’re not eliminated. That’s whytumors are able to grow and spread. The DRI is studyinghow tumors actually block the immune system fromtargeting and destroying them – and trying to turn thatinto a positive for type 1 diabetes.

Can something be learned from cancer – and protect isletcells from attack, too? Malignant tumors can producecertain molecules, “chemokines,” that help them escapedestruction. These molecules help suppress the immunesystem by recruiting a population of immune cells calledmyeloid-derived suppressor cells (MDSCs) to the tumor. The MDSCs block the immune system’s attack on the tumor cells.

Researchers want to use this same protective mechanismto stop an immune response to the body’s own insulin-producing islet cells (autoimmunity) or to newlytransplanted islets. The ultimate goal is to establishpermanent acceptance of the insulin-producing cellswithout the need for anti-rejection drugs. Currentlyavailable agents have been used to trigger the production

of MDSCs. DRI scientists believe that similar results may be achieved by giving the recipient a short course of thesechemokines at the time of islet transplantation.

In experimental models, Dr. Luca Inverardi, DRI’s deputydirector, and his immunology team, have achievedencouraging results suggesting that giving chemokines to recipients at the time of an islet transplant prolongs thesurvival of the tissue. During the past year, the researchershave also gained a greater understanding of why MDSCshave the ability to suppress the immune system’srecognition and reaction to unwanted cells.

They have been studying MDSCs taken from the umbilicalcord blood of healthy babies and learned that MDSCs arecapable of producing Regulatory T Cells (T-regs), which are critical in maintaining the immune system’s balance.

They have also observed that the increase in T-reg cells was dependent on the production of a key molecule (IDO).IDO activates the process that leads to immune toleranceduring pregnancy, which is why pregnant women are able to accept a fetus instead of rejecting it, even though the unborn child’s immune system is different than the mother’s.

The researchers have found MDSCs offer other potentialbenefits. As they began in-depth studies of the cells’characteristics, they discovered that these cells expressunique markers that also classify them as fibrocytes.Fibrocytes play a key role in promoting wound healing. The team believes that this novel discovery will have apositive impact on the use of these MDSC/fibrocytes forboth their powerful immunosuppressive properties as well as their ability to repair injured tissue.

The DRI's Biomedical and Immune Engineering team isexploring another approach to protect transplantedpancreatic islets without the need for any anti-rejectiontherapy. The focus: the molecule CCL21.

[ Dr. Alice Tomei and her team areinvestigating ways that tumors evadeattack by the immune system andapplying those findings to protect insulin-producing cells.


[ Dr. Antonello Pileggi and his team are investigating methods to reduce harmful inflammation that threatens the survival oftransplanted islet cells in the critical,early phase post-transplant

Dr. Alice Tomei, the DRI’s co-director of bioengineering, has shown that tumors release the molecule CCL21, which plays a central role in protecting them fromimmune attack. More recently, Dr. Tomei has applied thosefindings to cell transplantation in experimental models.She and her team engineered cells to express CCL21 withinthe transplanted tissue. They also engineered proteins to deliver CCL21 within a local transplant environment, such as a DRI BioHub. By delivering the molecule locally,many recipients accepted the cells – without systemicanti-rejection drugs.

Also, in preliminary studies, the team showed that theproduction of CCL21 in islets creates a lymph node-likeenvironment, removing unwanted cells that can promotean autoimmune response. Ongoing studies are looking at the mechanism by which these structures prevent the development of autoimmune diabetes in experimental models.

Preliminary evidence points to the involvement of certainstromal cells within these structures. Stromal cells are the connective tissue cells of any organ. The interactionbetween stromal cells and tumor cells is known to play a major role in cancer growth and progression.

Based on the initial findings, the team will conductadditional studies to further characterize these cells andthe role they can play in preventing the development ofautoimmunity, as well as the recurrence of autoimmunityafter islet transplantation.

CONTROLLING INFLAMMATION

As part of the multi-pronged approach to protect insulin-producing cells from immune attack, researchersare also aiming to quell the danger signals that cause

inflammation and are harmful to islet cells. Whensomeone gets a splinter in their finger, the immunesystem senses something foreign, and potentiallydangerous, and reacts immediately.

A series of highly-regulated, complex responses kick intogear – and the skin around the finger becomes inflamed. This process also occurs when transplanting islet cells. Theimmune system reacts to the biological “insult,” triggeringinflammation that can damage the transplanted cells and prompt further immune attacks.

Controlling inflammation is a major research priority and the focus of numerous studies aimed at protectingtransplanted islets, as well as the onset or recurrence ofautoimmune diabetes. DRI researchers are currentlypursuing two different approaches.

The DRI’s Dr. Antonello Pileggi and his team are workingwith a molecule that appears to be a critical player in activating inflammation: extracellular adenosine tri-phosphate (eATP). ATP serves as a source of energywithin each cell. In pancreatic beta cells, the release of low amounts of ATP is part of a sophisticated check-and-balance mechanism that regulates optimal cell function.

But when cells are stressed – by a biological insult or other unfavorable conditions (such as a transplant andautoimmunity development) – they release large amountsof ATP into the local environment (that is eATP). The team is assessing whether the release of high levels of ATP stimulates an immune response that, in turn,contributes to the destruction of the cells themselves.Initial studies in experimental models of islet, heart andlung transplantation demonstrated that, by blocking thefunction of eATP, they were able to reduce the activation of pro-inflammatory immune cells and, in turn, prolong the survival of transplanted tissues.


The studies also revealed a remarkable synergy whencombined with immune-modulating agents. The findings were the result of an international collaborative initiative with Professor Fabio Grassi at the Institute for Research in Biomedicine, Bellinzona, Switzerland, and Dr. Paolo Fiorina at Children’s Hospitals, HarvardUniversity in Cambridge, MA.

Their research led to the publication of three seminalmanuscripts that appeared in the peer-reviewed, scientificjournals, Diabetes (islet transplantation), Circulation (hearttransplantation), and American Journal of Respiratory Celland Molecular Biology (lung transplantation), respectively,as well as a recent review manuscript describing theworking hypothesis published in the American Journal ofTransplantation. The data has been presented at recentprofessional scientific meetings.

Having demonstrated the beneficial effects of the systemicmodulation of eATP signaling in transplantation models,the current efforts are concentrating on the role of eATP on islet immunogenicity and in the development of T1D.

Dr. Pileggi’s group is further pursuing this importantresearch to better understand the role and mechanismsassociated with the eATP pathway in islet immunity (innate immunity, rejection and autoimmunity), as well asidentifying other potential targets involved in this process.

The ultimate goal is to characterize the presence of specificsignaling molecules and test methods to modulate theimmune response and restore immune regulation in T1D,and protect islet transplants in the local microenvironment. This approach could result in synergy with cell-basedimmunotherapies aimed at protecting islet cells at the time of autoimmune diabetes onset as well as in a DRI BioHub.

In another approach, researchers are looking at a part of theimmune system – the TGF-ß molecule – that is supposed tocontrol inflammation. However, scientists have learned thatin certain diseases, a protein, Smad7, interferes with theTGF-ß pathway. The result: Smad7 promotes immune cellsignaling and immune responses.

The DRI is testing agents that block Smad7. This wouldallow TGF-ß to function properly and help regulateinflammation. Scientists already have identified atherapeutic agent that targets Smad7 and are using thisagent in clinical trials to treat inflammatory bowel disease(IBD), with encouraging early results.

In addition to preventing the inflammatory and immuneresponse associated with islet transplantation, there is also the intriguing possibility of preventing or evenreversing diabetes in new-onset patients. At the DRI, Dr. Peter Buchwald, director of drug discovery, and hiscolleagues have conducted preliminary studies showingthat, by inhibiting/blocking Smad7 at the time of diabetesonset, diabetes went into remission. More than half of thetreated models experienced normal blood glucose levelsand adequate insulin secretion – even long-term afterdiscontinuation of the treatment.

These results are particularly encouraging, raising thepossibility of reducing inflammation and controlling theimmune attack to the ongoing destruction of the insulin-producing cells in new-onset patients. This could also be beneficial to islet transplant recipients.

Ongoing studies are aimed at assessing the timing and dosing requirements needed for efficacy as well as assessing the mechanism of action. The researchers are also conducting larger-scale experiments needed toevaluate the potential of translating these encouragingresults into novel type 1 diabetes clinical trials.

[ Dr. Peter Buchwald is testing agentsthat prevent inflammation, as well as low-dose anti-rejection drugs that may be used locally within a DRI BioHub to prevent an immuneattack on the transplanted cells.


The DRI is also investigating the use of certain types of cells in the body that can hamper inflammation, promote tissue repair and enhance blood vessel growth.Mesenchymal stem cells, or MSCs, can become a variety ofcell types, including bone, cartilage and fat. They also haveseveral properties that can help improve the success ofislet transplantation.

DRI immunologists, along with colleagues on the tissueengineering team, have shown that by co-transplantinginsulin-producing cells with MSCs, they were able topromote blood vessel growth and tissue repair. Dr. NormaS. Kenyon, who heads the MSC research project, conductedpre-clinical studies using this combination of cells within asilicone scaffold, one of the platforms being tested for aDRI BioHub.

This BioHub platform was placed within an omentalpouch, which was created by folding a piece of the apron-like tissue covering the abdomen. This approach hasresulted in enhanced acceptance and extended viability of transplanted insulin-producing cells. With the support of a multi-center NIH grant, Dr. Kenyon and her colleaguesare now conducting research to identify the specificcharacteristics of the most effective MSC populations for islet transplantation and their incorporation into a DRI BioHub.

Once an effective MSC product is defined anddemonstrated to be optimal for intrahepatic (within the liver) islet transplantation, the same cells will beutilized in future tissue engineering experiments.

CELL ENCAPSULATION: PROTECTIVE BARRIERS FOR ISLETS

What if islet cells could be physically shielded from attackby immune system cells by encapsulating the cells in aprotective skin, or barrier?

For more than 40 years, the encapsulation of islet cells hasbeen researched as a potential therapy for type 1 diabetes.However, there has been limited success in translating thisapproach to patients due to a number of issues, includingthe size of the capsules themselves, the materials used tocoat the cells and the inability to provide the encapsulatedislets with enough oxygen to keep them healthy and functioning long term.

The DRI has been pursuing several strategies aimed atovercoming these challenges and has made significantprogress over the last year. The bioengineering team has invented and optimized several new technologies to individually coat the islets in ultra-thin layers thatcamouflage them from the recipient’s immune system. By minimizing the space surrounding the islet cell, notonly can they enhance the oxygen and nutrient delivery to the cells, but also have the ability to transplant the cells within a DRI BioHub.

The DRI’s Dr. Cherie Stabler and her team have invented a technology that generated nanoscale (less thanmicroscopically thin) coatings onto islets. This is achievedby “dipping” the cells in polymers to create individuallayers. Nanoscale, or layer-by-layer, encapsulation is atechnique that has been used for decades in theelectronics, optics and sensor industries.

[ Dr. Norma Kenyon and her teamconducted pre-clinical studies testingthe co-transplantation of islets andmesenchymal stem cells (MSCs)within a DRI BioHub platform.


This encapsulation methodology provides significantcontrol over the properties of the layers, resulting in a coating that is 500-fold smaller than conventionalmicrocapsules. The team’s recently published study in the journal Advanced Healthcare Materials is the first to show that layer-by-layer nanoscale coating can prevent rejection of transplanted islets in rodents,resulting in long-term function. This is a major stepforward in nanoscale encapsulation research. Theselayered coatings also provide a platform for attachingimmunomodulatory agents to the surface of the cells that can help fight off an immune attack.

Dr. Alice Tomei and her team are developing anotherencapsulation strategy, the conformal coating process, that “shrink wraps” each islet cell with the coating material as it passes through a special microfluidic system. As with a person’s own skin, which has smallpores that provide protection and allow oxygen to enter,cell coatings must be designed in much the same way. The pores need to screen out destructive immune systemcells but allow oxygen, glucose (blood sugar) and insulinto easily pass through.

Over the last two years, the team has demonstrated long-term immunoprotection of transplanted isletsencapsulated with conformal coatings in rodent models of diabetes. In these studies, diabetes was reversed in less than two weeks and the coatings were able to protect transplanted islets from rejection whilemaintaining normal blood sugar levels in the experimental models. The islets continued to function long term without the use of any anti-rejection drugs. The team is currently reproducing these results in a larger cohort of experimental models, in larger pre-clinical models, and in clinically relevant sites.

DRI scientists are also tackling another major factor thatinhibits islet engraftment – the lack of adequate oxygen in the immediate post-transplant period. After islets aretransplanted into a patient, it takes several weeks for newblood vessels to form, which transport the critical oxygenand nutrients these cells demand. Closing this oxygen gap is a top priority for healthy islet function.

Several approaches are underway to address this issue.First, the use of specific growth factors released in acontrolled manner, which have been successful in speeding blood vessel development (as early as seven days after transplant) and improving post-transplant islet function and reducing islet loss. Alternatively, in aunique approach to oxygen delivery, DRI researchers arefocusing on incorporating oxygen directly within each capsule by mimicking a process that occurs in nature every day – photosynthesis.

Plants convert sunlight and water into its components, one of which is oxygen. Dr. Chris Fraker has developed a

similar process in the lab using naturally-occurring metals (minerals) that can, under the proper conditions, generateoxygen spontaneously from water. A side benefit to thisapproach is that these metals can also scavenge freeradicals and other damaging particles by converting thoseinto oxygen in addition to other harmless components. He and his team are making microscopic particles(nanoparticles) out of the metals and incorporating theminto the polymers used to encapsulate the cells, givingthem a type of built-in oxygen provider. The nanoparticlescan be used together with any type of biomaterials usedfor the coatings, as well as being incorporated within aBioHub platform, to increase oxygen levels and improvetransplant outcomes.

>

An Eye on Immune ToleranceDRI scientists have been working to determine if the successful achievement of immunetolerance through the anterior chamber of the eye will allow for survival of transplanted islets without immunosuppression. Followingtheir cover-featured publication in the peer-reviewed journal Diabetologia, which reported on the use of the anterior chamber of the eye as a transplantation site in pre-clinical models totreat type 1 diabetes, Drs. Per-Olof Berggren,Midhat Abdulreda, Norma Kenyon, and DoraBerman-Weinberg developed a collaboration with researchers from Seoul National University in Korea to further investigate this approach andhelp establish it as a clinical transplantation site.Studies have been ongoing concurrently in Seouland at the DRI in Miami. These studies explore the feasibility of intraocular islet transplantationin pre-clinical models of type 1 diabetes.


LOCAL DRUG DELIVERY

The development of a DRI BioHub provides the ability toincorporate anti-inflammatory and anti-rejection drugswithin the bioengineered device. Local drug delivery iscommonly used in a variety of treatments requiring anti-inflammatory steroid delivery and hormone therapy. DRI researchers are testing similar approaches to those in use for these conditions, such as thin rods and drug-eluting polymers for the long-term, sustained release oftherapeutic agents as a means of protecting transplantedislets within the local environment. This could allow for the use of much smaller local doses and avoid or minimizethe systemic side effects of current therapies.

The DRI’s bioengineering team, in conjunction with Dr. Peter Buchwald, head of DRI's drug discovery program,is using a unique embedding and coating process todeliver sustained-released drugs that are known tominimize this initial immune inflammatory response.

This past year, the team tested several combinations ofdrugs to determine the best results. The local delivery oflow-dose anti-inflammatory and/or anti-rejection drugs at the transplant site offers the opportunity to minimize or maybe even eliminate the current, systemic drugs that pose so many unwanted side-effects.

TARGETING CELLS IN VIVO

Researchers continue to develop new and significantlymore precise methods to deliver desired molecules and other agents to targeted cells within the body or in a DRI BioHub. New advances in imaging andnanotechnology are allowing scientists to test a special class of molecules which are, essentially, the chemical equivalent of antibodies.

Known as aptamers, these tiny strands are able to hone in and bind to specific targets on the cell surface.Aptamers are an attractive alternative to previous drugdelivery techniques due to their small size and relativelylow production cost. Aptamers also have the advantage of being highly specific, meaning they can bind to targeted cell markers without eliciting a foreign tissue (immune) response.

The DRI team, including Drs. Luca Inverardi, Paolo Serafini,Alessia Zoso, and Giacomo Lanzoni, have selectivelyscreened for aptamers unique to islets and beta cells forthe rodent model. The team is now focused on adaptingthe same methods to create an aptamer library specific to human islets and beta cells.

The team is also using this novel technology to "tag" living insulin-producing cells within the native pancreas or in a DRI BioHub by attaching fluorescent markers to the aptamers. After binding to the targeted islet/beta cell, sophisticated scanners will be able to pick up thefluorescently-labeled islets, providing valuable informationas to the quantity of living islets/beta cells and theirlocation. The team is also adapting this technology for itsuse with clinical instruments, such as Magnetic ResonanceImaging (MRI), that is routinely used in the clinic. This willalso allow for the delivery of anti-inflammatory and/oranti-rejection agents directly to the desired cells instead of shutting down the entire system with systemicimmunosuppression.

Since the discovery of aptamers in the early 1990s, greatefforts have been made to make them clinically relevantfor diseases like cancer, HIV, and macular degeneration. Inthe last two decades, many aptamers have been clinicallydeveloped and FDA approved. In 2004, aptamer-basedtherapy was approved for the treatment of age-relatedmacular degeneration and several other aptamers arecurrently being evaluated in clinical trials.

[ Drs. Alessia Zoso and Paolo Serafini are part of theteam that is testing a special class of molecules,called aptamers, that bind to insulin-producing beta cells. The aptamers enable researchers toattach markers directly to the cells in order to track and image the living cells in the body.


Area 3 Supply

Currently, islets used for transplantation come from the pancreases of deceased donors. With organ donation in the United States at critically low levels – about 1,700 pancreases were available last year – there is clearly not enough supply to treat the millions of children and adults living with diabetes.

The DRI is pursuing severalstrategies to develop areliable supply of insulin-producing cells. Identifyingthe right stem cells – thosewith the potential tobecome islet cells – is a key step for the design of cell replacement,regenerative andreprogramming strategies.

At the DRI, researchers are using certain populations of stem cells, as well as reprogramming other cells of the body that have an entirely different function to becoming insulin-producing cells.

THE BILIARY TREE: A NOVEL SOURCE OF INSULIN-PRODUCING CELLS

An area that has sparked great interest is the discovery of stem cells in the "biliary tree" – a network of drainageducts that connect the liver and pancreas to the intestine.

DRI scientists are interested in these cells because they are pancreatic "precursor" cells – that is, they already havestarted down the path to become pancreatic cells. This couldmake it easier for scientists to produce a more efficientmaturation and a higher yield of islet cells.

The DRI’s Drs. Luca Inverardi, Giacomo Lanzoni and JuanDominguez-Bendala are collaborating with Dr. Lola Reidfrom the University of North Carolina, a recognized expert in liver development and regeneration, who discoveredthese peculiar stem cells.

In the past year, they showed that stem cells within thebiliary tree can transform into both liver and pancreatic cells, including insulin-producing islet cells. They obtainedthe pancreatic precursor cells from the biliary tree. Theresearchers then cultured these cells with a mixture ofgrowth factors and components found in the natural isletenvironment. These molecular signals instruct the cells tomature into islets. The process resulted in structures that looked like islets and contained both insulin- andglucagon-producing cells.

These islet structures released insulin and C-peptide (acomponent of natural insulin production) in response toglucose challenges. The researchers demonstrated thattransplanting these structures into diabetic micedramatically improved blood sugar control.

The group has identified an extended network of stem cell pockets that branch out from the more naïve stem cells in the biliary tree to more and more mature cells in the pancreas and liver. These findings suggest that thedevelopment of the pancreas does not come to an end inadulthood and may continue as a life-long process that can regenerate the stressed organ, islet cells included. The investigators are scaling up these findings and testingregenerative strategies based on biliary tree stem cells fortype 1 diabetes.

As a result of this collaboration between Miami and Chapel Hill, several research papers have been published inprestigious journals, and others are in press. A paper titled“Biliary Tree Stem Cells, Precursors to Pancreatic CommittedProgenitors: Evidence for Possible Life-long PancreaticOrganogenesis” appeared in the journal Stem Cells, alongwith a review on “Clinical programs of stem cell therapiesfor liver and pancreas.”

Ongoing studies are aimed at establishing proof of concept that these cells can be used to reverse diabetes in pre-clinical models. The team is also assessing optimal implantation sites as well as strategies to aid in “transforming” or differentiating these pancreaticprecursors by mimicking the critical components of theirnative environment combined with newly discovered islet-specific growth factors.

REPROGRAMMING THE NON-ISLET TISSUE OF THE PANCREAS INTO INSULIN-PRODUCING CELLS

Rather than educating a stem cell from its earliest stages ofdevelopment – pushing it down the long path to become anislet-type cell – transdifferentiation can potentially offer ashort cut. In this approach, scientists take a more maturecell type and “reprogram” it, transforming it directly into aninsulin-producing cell.


To accomplish this, the DRI has been focusing on the part of the pancreas that does not produce insulin: the non endocrine pancreatic tissue, or NEPT. NEPT makes up almost 98 percent of the organ. It helps process food by producing digestive enzymes. NEPT typically is discarded after an islet isolation procedure. Since the DRI is a leading islet isolation facility, it has a plentiful supply of NEPT.

One of the interesting features of NEPT is its high plasticity – its ability to turn into other cell types or tissues. At the DRI, Drs. Juan-Dominguez-Bendala, Ricardo Pastori and Luca Inverardi are developing andtesting new methods to reprogram human NEPT intoinsulin-producing cells. The team is assessing whether this tissue can be transformed and used as a source for cell transplantation.

During the past year, the researchers discovered that, once placed in culture, these cells tend to lose their identity within days, progressively becoming a cell type called “mesenchymal” that is virtually useless forreprogramming purposes. This “degradation” process isknown as Epithelial to Mesenchymal Transition (EMT). The team took the novel approach of adding a currentlyavailable agent to the culture – and successfully blocked EMT. This led to robust reprogramming and anextraordinary yield of NEPT into insulin-secreting cells.

The ability to chemically block EMT allowed for thegeneration of cells that secrete insulin in response toglucose with total insulin levels comparable to those of native islets. Importantly, preliminary experimentsshowed that reprogramming is also possible using frozen NEPTs. This could be important for clinical islettransplantation because, down the line, it might allow for a second infusion of insulin-producing cells from the same donor.

The DRI is now focused on optimizing the culture conditions to induce reprogramming into insulin-producing cells and subsequently transplanting these cells in experimental models. They will also optimizeconditions for reprogramming of previously frozen NEPTs. Additional research will focus on identifying subsets of cells within the NEPT that may be more prone to islet cell reprogramming.

CONVERTING SKIN FIBROBLAST CELLS INTO BETA CELLS

When a stem cell is undifferentiated or uncommitted –before it “decides” to become a certain kind of cell – its DNA is “loose.” It’s able to develop into many cell types. This ability is known as “pluripotency.” As a cell develops and commits to a specific function, its DNA “hardens.” But scientists are now able to “loosen” the DNA of an adult, committed cell. And that cell can regain some degree of pluripotency. This “loose” state does not last long, but long enough for scientists to push the cell down a new path to become a different kind of cell.

DRI collaborators at the University of Milan, Italy, led by Dr. Tiziana Brevini, recently developed a method toconvert skin “fibroblast” cells into insulin-producing betacells. Fibroblasts are found throughout the human body.These cells are known as pancreatic epigenetic convertedcells (EpiCC). They show many characteristics of mature beta cells and also include other key endocrine cells of healthy islets.

As reported in the May, 2013 Proceedings of the NationalAcademy of Science (PNAS), studies have demonstrated that the EpiCC are able to secrete C-peptide in response to glucose and maintain this ability for more than 100 days.

[ Drs. Juan Dominguez-Bendala(standing, left), Luca Inverardi and Ricardo Pastori (seated) aredeveloping and testing methods toreprogram the nonendocrine tissueof the pancreas to increase thesupply of insulin-producing cells.


TrialNet has conducted several studies aimed at slowing the immune system’s attack on insulin-producing cells in people newly diagnosed with type 1 diabetes. Two of the studies that TrialNet has conducted, and a thirdorganized by the Immune Tolerance Network with TrialNetparticipation, have identified drugs with promise of benefit.Currently, TrialNet is focused on altering the immunesystem attack in order to delay or prevent type 1 diabetes in relatives found to be at risk for the disease. Threeprevention studies are ongoing – using oral insulin, the

immune co-stimulation blocking drug abatacept, and amonoclonal antibody targeting activation of the immunesystem. In addition, TrialNet is poised to launch additionalstudies in people newly diagnosed with type 1 diabetes.The studies are conducted by the National Institutes ofHealth’s international network of researchers, Type 1Diabetes TrialNet Study Group, which is housed at the DRI, under the direction of Dr. Jay Skyler, TrialNet nationalchairman. To learn more about TrialNet, visitwww.DiabetesTrialNet.org.

[ Dr. Jay Skyler, DRI deputy director, serves as study chairman for the NIH-sponsoredTrialNet, an international networkconducting clinical trials to prevent, delay and reverse type 1 diabetes.

When injected into diabetic mice, EpiCC, which were developed from human skin cells, quickly restored normal blood glucose levels. All mice were able to maintain these levels for 133 days, at which time the EpiCC were removed.Subsequently, a rapid increase of blood sugar was observedalong with an equally rapid loss of detectable human insulin, which was previously present.

Preliminary results indicate that EpiCC may be converted into insulin-expressing cells. The researchers will continue to characterize the converted fibroblasts, following the method developed in the Brevini lab, to evaluate insulinproduction and other characteristics of pancreaticendocrine cells.

The DRI is pursuing the potential of using EpiCC as analternative source because such cells could provide a nearlimitless supply of insulin-producing cells in response to changing levels of glucose. In addition, the converted skin cells obtained from the patient would not be seen as “foreign” and therefore would not be rejected, which occurs with transplanted cells from another donor.

TRIALNET UPDATE

The research projects that comprise the DRI BioHub receive critical philanthropic support from the DiabetesResearch Institute Foundation. Funding for the DRIBioHub is also provided by other sources including the ADA, JDRF, The Leona M. and Harry B. HelmsleyCharitable Trust, National Institutes of Health (NIH), NIH Small Business Innovation Research, Ri.MEDFoundation, University of Miami, and additional public and corporate partners.


THE DIABETES EDUCATION ANDNUTRITION SERVICE AT THE DRI

Looking back over the past 12 months:

• More and more patients are being referred to the DRI’s unique education program, and these patientscome from the DRI Clinic, University departments,including Pediatric Endocrinology, and a growingnumber of community providers. The recent closure of three large, community-based diabetes educationprograms over the past two years has made theservices provided by the DRI even more crucial forpatients and their families.

• With over 8,000 visits captured, the DRI’s use of aninnovative data management system has enabledoptimization of existing services and targetedimprovements of internal processes and futureprovision of services.

• The DRI team continues to be involved in professionaland community outreach initiatives, including but not limited to:

– UM campus and community health services, including expansion sites throughout South Florida

– Florida International University Dietetic StudentInternship Program

– Local professional presentations by the American Diabetes Association, Health Choice Network, National Podiatry Association and the University of Miam iGrand rounds

– Professional Association Positions (NCBDE, AADE,GMADE)

– Diabetes Research Institute Foundation – PEP(Parents Empowering Parents) Squad and ‘Top Tips’ articles

– Seminole Media Productions

• The DRI Diabetes Education and Nutrition Service also coordinated more than a dozen clinical experience training programs during the past year, up-skilling industry representatives on the medical and education standards for diabetes care. Over 800 representatives attended, with outstanding program satisfaction ratings across all programs offered.

With an eye toward the future, the DRI DiabetesEducation and Nutrition Service is updating its verysuccessful educational curriculum to continue thecurrent class schedule (e.g., Healthy Me, Diabetes Made Simple, Pump Training and the highly acclaimedMastering Your Diabetes program), and is adding several innovative components in the near future:

• A DRI online, interactive diabetes education program,tailored for health care professionals involved in thecare of people living with diabetes.

• A multi-disciplinary Transition Program, to assistchildren and parents in transition from pediatric to adult-based diabetes management and care

• A Diabetes Prevention Recognition Program (based on CDC and AADE program standards)

The past year has represented one of transition – education team members leaving for new professionalopportunities and new education team members coming to the DRI to experience the incredible educationalofferings that comes from working with highly-skilled providers and researchers. New leadership is already in place with the directorship being shared by two past DRI diabetes educators, Lisa E. Rafkin, MS, RD, LD, CDE, CCRC,research assistant professor of medicine, and Della Matheson, RN, CDE, both of whom have worked for many years at the DRI in the area of clinical research, and on the DRI diabetes management team under the guidance of Dr. Jay Skyler some 20 years ago. They will be joined by several newly hired specialists, including dietitians and certified diabetes educators, so that they will be able to meet the increasing demand for patient education and medical nutrition therapy at the DRI.

The program remains certified as an American Diabetes Association’s Education Recognized Program, which enables collection of revenues for education and nutrition services. Under Dr. Skyler’ s supervision, the new team will continue to strive for excellence and continued improvement in overall patient services.

The Diabetes Education and Nutrition Service at the DRI’s Eleanor and Joseph Kosow Diabetes Treatment Center continues to use collaboration,innovation, integration and evaluation as the driving forces behind its patient initiatives.


DIABETES RESEARCH INSTITUTE FACULTY AND STAFF

Dr. Camillo RicordiStacy Joy Goodman Professor of SurgeryDivision of Cell TransplantationDistinguished Professor of MedicineDirector, Diabetes Research Institute and

Cell Transplant Center

Dr. Midhat H. AbdulredaAssistant Professor of SurgeryDivision of Cell Transplantation

Dr. Rodolfo AlejandroProfessor of MedicineDirector, Clinical Cell Transplant Center Associate Director of Clinical ResearchAssociate Director, Cell Transplant Center

Dr. Allison BayerResearch Assistant Professor of

Microbiology and Immunology

Dr. Per-Olof BerggrenMary Lou Held Visiting ScientistAdjunct Professor of SurgeryHead of Cell Biology and Signal TransductionProfessor and Head, Experimental

Endocrinology at the Karolinksa Institute, Sweden

Dr. Dora Berman-WeinbergResearch Associate Professor of Surgery

Dr. Peter BuchwaldAssociate Professor of Molecular and

Cellular Pharmacology Director, Drug Discovery Program

Dr. Juan Dominguez-BendalaResearch Associate Professor of SurgeryDirector, Stem Cell Development for

Translational Research

Dr. Chris FrakerResearch Assistant Professor of Surgery

Division of Cell Transplantation

Dr. Jeffrey HubbellAdjunct Professor of Surgery Director, Integrative Biosciences InstituteInstitute for Chemical Sciences and

Engineering at Ecole Polytechnique Fédérale de Lausanne, Switzerland

Dr. Luca InverardiResearch Professor of Medicine,

Microbiology and ImmunologyDirector, Immunobiology of Islet

TransplantationDeputy Director for Translational Research

Dr. Norma S. KenyonMartin Kleiman Professor of Surgery,

Medicine, Microbiology and Immunology, and Biomedical Engineering

Director, Wallace H. Coulter Center ForTranslational Research

Chief Innovation Officer, University of Miami

Dr. Jennifer MarksProfessor of MedicineDivision of Endocrinology, Diabetes

and Metabolism

Dr. Armando MendezResearch Associate Professor of MedicineDivision of Endocrinology, Diabetes

and MetabolismDirector, Advanced Technology Platforms

Dr. Daniel H. MintzScientific Director EmeritusProfessor Emeritus of Medicine

Dr. Bresta Miranda-PalmaAssistant Professor of MedicineInterim Director, Eleanor and Joseph Kosow

Diabetes Treatment Center Division of Endocrinology, Diabetes, and Metabolism

Dr. Ricardo PastoriResearch Professor of Medicine,

Immunology and MicrobiologyDirector, Molecular Biology Laboratory

Dr. Maria del Pilar SolanoAssistant Professor of Medicine

Dr. Antonello PileggiResearch Associate Professor of SurgeryDirector, Pre-Clinical Cell Processing and

Translational Models

Dr. Alberto PuglieseResearch Professor of Medicine, Microbiology

and ImmunologyDirector, Immunogenetics Program

Dr. Jay Skyler Professor of Medicine, Pediatrics

and PsychologyDivision of Endocrinology, Diabetes

and MetabolismDeputy Director for Clinical Research

and Academic Programs, Diabetes Research Institute

Chairman, NIDDK Type 1 Diabetes TrialNet Study Group

Dr. Cherie StablerAssociate Professor of Biomedical

Engineering, SurgeryDirector, Tissue Engineering Laboratory

Dr. Alice TomeiResearch Assistant Professor of Surgery Division of Cell Transplantation

Faculty


DIABETES RESEARCH INSTITUTE FACULTY AND STAFF

AdministrativeDr. Mitra Zehtab,Chief Operating Officer and Deputy DirectorMabel Luis, Executive AssistantDora Cardenal, Director, Accounting

Sabrina Boulazreg, Sr. Manager, Business Operations

Angie Arzani, Sr. Manager, Finance

Juan Perez-Scholz, Manager, Sponsored Programs

Ligia Delgado, Sr. Accounting AssistantGrace Perez, Sr. BuyerMarc Friedenthal, BuyerIlvis Torres, Administrative Assistant

Medical DevelopmentGary Kleiman, Sr. Development Director, Major GiftsAimee Siegel-Harris, Manager, Donor Relations

BioengineeringDr. Chris Fraker, Research Assistant Professor of Surgery

Dr. Alice Tomei, Research Assistant Professor of SurgeryVita Manzoli, Sr. Research Associate 1Mejdi Najjar, Research Assistant Professor 1Chiara Villa, Non-Enrolled Fellow

Bio-Informatics Roopesh Sadashiva-Reddy,Database Administrator

Clinical Chemistry LabDr. Armando Mendez,Research Associate Professor of

Medicine, Director

Dr. Ronald B. Goldberg,Professor of Medicine

Dr. Marcos Levy-Bercowski, Voluntary Assistant Professor of SurgeryDr. Monia Cecati, Research Scholar

Esperanza Perez, Supervisor, Medical Technologists

Rosa Hernandez, Research Associate 1 Elsa Cribeiro, Sr. Research AssistantZackary Barnes, Sr. Research Assistant

Clinical Cell Transplant Program (CCTP) Dr. Rodolfo Alejandro, Professor of Medicine, Director Dr. Eduardo Peixoto, Assistant ScientistAna Alvarez Gil, ARNPAlina Cuervo, Sr. Medical Biller

Clinical Research Center Dr. Bresta Miranda-Palma, Assistant Professor of Medicine, DirectorBurlett Masters, Research Support SpecialistAda Konwai, Sr. Research Assistant

Diabetes Prevention Program (Type 2) Dr. Ronald B. Goldberg, Professor of Medicine, Director Juliet Ojito, Nurse Specialist, ResearchJeanette Gonzalez-Calles,Research AssociateMaria Valbuena, Research Associate 1Bertha Veciana, Medical AssistantWanda Ramirez, Secretary

Drug Discovery Program (DPP)Dr. Peter Buchwald, Associate Professor

of Molecular and Cellular Pharmacology,Director

Dr. Sirlene Cechin, Assistant ScientistDr. Jinshui Chen, Post-Doctoral Associate Omar Lopez-Ocejo, Research Associate 1Yun Song, Student Research Assistant

Eleanor and Joseph Kosow Diabetes Treatment Center

Faculty Dr. Ronald B. Goldberg, Professor of Medicine

Dr. Jennifer Marks, Professor of Medicine

Dr. Daniel H. Mintz, Professor Emeritus of Medicine

Dr. Bresta Miranda-Palma, Assistant Professor of Clinical of Medicine,

Interim Director

Dr. Maria del Pilar Solano, Assistant Professor of Clinical of MedicineDr. Jay Sosenko, Professor of Medicine

Dr. Jay S. Skyler, Professor of Medicine, Pediatrics and

Psychology

Dr. Lisa Rafkin-Mervis, Research Assistant Professor of Medicine

Health Care Professionals Lory Gonzalez, Nurse EducatorGwen Enfield, Clinical Dietitian Amy Kimberlain, Dietitian

Clinical Administration Dina Bardales, Supervisor, Patient AccessArleen Barreiros, Project CoordinatorStarlette Canamero, Sr. Administrative Assistant


Flow Cytometry Lab Dr. Oliver Umland, Assistant Scientist

HistologyKevin Johnson, Sr. Research Associate 3

Human Cell Processing (cGMP) FacilityDr. Luca Inverardi, Research Professor of

Medicine, Facility Director

Dr. Elina Linetsky, Director, Interim Director Laboratory Services

Dr. Joel Szust, Scientist

Dr. Alejandro Alvarez-Garcia, Associate ScientistDr. Xiao Jing Wang, Associate ScientistDr. Greta Minonzio, Research ScholarDr. Muyesser Sayki, Research Scholar

Carmen Castillo, Research Laboratory Technician

Image Analysis FacilityDr. Marcia Boulina, Assistant Scientist

Immunobiology of IsletTransplantationDr. Luca Inverardi, Research Professor of

Medicine, Director Dr. Alessia Zoso, ScientistDr. Giacomo Lanzoni, Assistant ScientistDr. Sophie Borot, Research ScholarMatteo Battarra, Research Scholar

Immunogenetics ProgramDr. Alberto Pugliese, Research Professor

of Medicine, Director Dr. Francesco Vendrame, ScientistDr. Isaac Snowhite, Research Scholar Gloria Allende, Sr. Research Associate

Islet PhysiologyDr. Per-Olof Berggren, Adjunct Professor

of Surgery, Director Dr. Midhat Abdulreda, Assistant Professor of SurgeryDr. Joana Almaca, Research ScholarAlexander Shishido, Research Associate 1

Microbiology and Immune ToleranceDr. Tom Malek, Professor of Microbiology

and ImmunologyDr. Allison Bayer, Assistant Professor of

Microbiology and Immunology Dr. Allison Bayer, Assistant ProfessorCecilia Cabello, Research Associate 3 Shane Mackey, Research Associate 1

Molecular BiologyDr. Ricardo Pastori, Research Professor

of Medicine, DirectorDr. Dagmar Klein, Scientist

Fast TrackDr. Camillo Ricordi, Stacy Joy GoodmanProfessor of Surgery, DirectorXiumin Xu, Director, DRI-China, Collaborative

Human Cell Transplant ProgramyDr. Fanuel Messaggio, Post-Doctoral

Associate Marta Garcia Contreras, Sr. Research

Associate 1

Pre-Clinical Cell Processing andTranslational ModelsDr. Antonello Pileggi, Research Professor

of Surgery, Director Dr. Ruth Damaris Molano, Scientist

and Core DirectorDr. Carmen Fotino, Assistant Scientist Dr. Ulissi Ulisse, Research Scholar Alejandro Tamayo-Garcia,

Research Associate 1Yelena Gadea, Sr. Veterinary TechnicianAdriana Lopez-Ospina, Research Assistant

Pre-Clinical Research Dr. Norma Sue Kenyon, Martin Kleiman

Professor of Surgery, DirectorDr. Dora Berman-Weinberg, Research Associate ProfessorDr. Dongmei Han, ScientistDr. Ana Hernandez, Associate ScientistWaldo Diaz, Sr. Manager, Research LaboratoryMelissa Willman, Sr. Manager, Research Support

Alexander Rabassa, Sr. Research Associate 3James Geary, Sr. Veterinary TechReiner Rodriguez-Lopez, Veterinary Technician

Stem Cell Development forTranslational Research Dr. Juan Dominguez-Bendala, Research

Associate Professor of Surgery, DirectorDr. Sara Garcia Serrano, Research ScholarSilvia Alvarez, Manager, Research Laboratory

Tissue EngineeringDr. Cherie Stabler, Associate Professor of

Biomedical Engineering, Director Dr. Jeffrey Hubbell, Adjunct Professor

of Surgery Dr. Kerim Gattas-Asfura, Associate ScientistJoshua Gardner, Sr. Research Associate 1Irayme Labrada-Miravet, Research AssistantMaria Coronel, Student Research AssistantAnthony Frei, Student Research AssistantJaime Giraldo, Student Research AssistantKaiyuan Jiang, Student Research AssistantMike Valdes, Student Research AssistantEthan Yang, Student Research Assistant

Diabetes TrialNetDr. Jay Skyler, National ChairmanDr. Norma Sue Kenyon, Associate Chair for ImmunologyDr. Jennifer Marks,Principal Investigator –TrialNet Clinical CenterDr. Alberto Pugliese, Co-Investigator, Clinical CenterDr. Gerit Holger-Schernthaner, Voluntary Assistant Professor of SurgeryDr. Lisa Rafkin-Mervis, Study Co-ChairmanDr. Luz Arazo, Clinical Research CoordinatorDr. Carlos Blaschke, Clinical Research CoordinatorDella Matheson, Trial CoordinatorNatalia Sanders, Research Associate 1Irene B. Santiago, Sr. Administrative AssistantElizabeth Machado, Administrative

Assistant


Those who are involved with the Diabetes Research Institute Foundation, like my wife,Kelly, and I, want nothing more than to find a cure for their loved ones, themselves, andmillions of others who have diabetes. Despite the many advances that have been made in managing diabetes, none of us is content to just live with this disease. Certainly, peoplewith T1D have benefited from advances in management and treatment, but our focus ison a cure so we can render all of that moot.

The DRI’s cure-driven mission exemplifies why an ever-growing circle of passionate and committed people have chosen to invest their support – in both time and money – here.

More than a decade ago, when I first learned about the DRI, it marked the first time that I really felt there was a strategy in place for Reaching the Biological Cure. In the years since, while we have seen wonderful progress toward that goal, we continue to feel an urgent need to cross the finish line for our son, Will, and for every other family affected by diabetes.

DRIFChairman's Message


This past year, the unveiling of the DRI BioHub, coupled withthe Institute’s plans to initiate Phase I/II clinical trials in 2014,has further cemented my belief that we are on our way toending diabetes once and for all.

Subsequent to the BioHub roll-out, the DRI Foundationreceived a number of significant contributions from donorswho recognize the inherent promise of this ground-breakinginitiative – and, also, are acutely aware of the tremendousinvestment in research that is needed to bring the BioHub tofruition. While we have witnessed a successful year in terms ofour fundraising – one in which we were able to direct a greaterlevel of funding to our scientists – these gifts represent a merefraction of the resources necessary to get this job done.

The overwhelming need for research funding is palpable and serves as the driving force behind all of our activities.Having streamlined our operating expenses over the pastseveral years, we were in a strong position to move forward and maximize the revenue we transferred to the DRI for BioHub programs. In turn, that support helped to deliver these research advancements.

We allocated the DRIF’s funding, which came from generouspeople like you, to a number of projects within the majorscientific areas that comprise the DRI BioHub: the Site,Sustainability, and Supply. As summarized in the ResearchReview section of this report, our DRI scientists have made progress in these areas across the board, and havedemonstrated encouraging results that are moving into the next phases of testing.

Undeniably, the most exciting news centers on the DRI’s plan to begin pilot clinical trials in 2014. Demonstrating theircommitment to bringing the most promising findings fromthe lab to patients with type 1 diabetes, DRI scientists will testwhether an alternative site in the body – the omentum – is amore ideal home for transplanted islet cells than the liver. In this trial, the islet cells will be implanted within a“biodegradable scaffold,” one of the platforms originallyconsidered for a DRI BioHub. Plans are also underway toutilize the omentum as a site for a second BioHub platform, a “bioengineered scaffold,” once approval is obtained from the regulatory bodies.

As you read in Dr. Ricordi’s message, the research process is not without its hurdles, and unforeseen delays certainly extend the timeline for moving our work forward. What we cannot and should not accept, however, is for the lack ofadequate funding to be an additional impediment to progress.As those of us who are affected by this devastating diseasewell know, tomorrow is not soon enough to find a cure.

Thankfully, numerous individuals, families, businesses, andfoundations have played a huge role in bolstering our efforts to further the research this past year. None of this work wouldhave been possible without the extraordinary contributionsfrom those who have made supporting cure-focused researchtheir top priority. Many of these donors are pictured on thefollowing pages. On behalf of the entire organization, I want to extend our deepest gratitude to them and countless others for their generosity and tireless efforts.

While this past year has been one of significant advances, itwas also a year of transition as we welcomed new leadershipat the Diabetes Research Institute Foundation with theappointment of Joshua Rednik as president and CEO. Josh, who brings with him almost two decades of experience infundraising organizations, will help guide the Foundation intoan exciting era for those living with this disease. I, togetherwith my board colleagues, have the highest confidence in his ability to lead with distinction and integrity.

A new governance structure for the Northeast Region wasadopted and new co-chairs were appointed. The members of the new Northeast Region Executive Committee and Board are a strong contingent of new and veteran leaders, each of whom has a personal stake in fulfilling our mission.This group of individuals joins our National and Florida Region leadership in ensuring the highest standards of fiscal oversight, accountability, and donor stewardship.

As we head into the next year with excitement andoptimism, we hope we can count on your continuedsupport to make our progress possible. Thank you again for your generosity and friendship.

Sincerely,

Harold G. Doran, Jr. Chairman

Research Funding is CriticalThe Diabetes Research Institute Foundation provides the DRI with critical seedfunding to gather data that is often a prerequisite for larger grants. The mission – to provide the Diabetes Research Institute with the funding necessary to curediabetes now – is a testament to the belief that tomorrow is not soon enough to cure this disease. The DRIF's funding stream is at the heart of DRI’s ability toinnovate and make significant strides toward a cure. In addition to receiving the DRIF's support, DRI scientists have been awarded competitive grants fromnumerous funding entities for almost 40 consecutive years.


FinancialSummary

Through the support of private philanthropy, the Diabetes Research Institute Foundation has funded six chairs totaling almost $13 million.

The J. Enloe and Eugenia J. Dodson Chair in Diabetes Research

Stacy Joy Goodman Chair in Diabetes Research

Mary Lou Held Chair for Diabetes Research Martin Kleiman Endowed InvestigatorshipDaniel H. Mintz Visiting ProfessorshipRicordi Family Chair in Transplant Immunobiology.


Diabetes Research Institute FoundationStatement of Activities for the Year ended June 30, 2013

Support and RevenueContributions $7,144,705 Reimbursement Contracts 184,950 Special Events, net of expenses 4,332,230 Investment Income 1,006,302

Total Support and Revenue 12,668,187

Expenses and Fund Balances

Program ServicesResearch provided to the Diabetes Research Institute 7,031,358 Community Education 804,661

Total Program Services 7,836,019

Support ServicesAdministration and General 1,610,401 Fundraising 1,765,139

Total Su pport Services 3,375,540

Change in Net Assets 1,456,628

Net Assets, Beginning of Year 24,850,703

Net Assets, End of Year $26,307,331

Fundraising Percentage

Fundraising Expense as a Percentage of Support and Revenue 14%

Diabetes Research Institute Statement of Activities

Support and Revenue

Diabetes Research Institute Foundation $7,031,358 40%National Institute of Health 6,455,822 36%JDRF Grants* 2,104,852 12%Kosow Center 1,094,725 6% University of Miami 491,940 3%Corporate Grants 405,718 2%American Diabetes Association/

American Heart Association Grants 51,566 .5%State of Florida Education Grant 34,708 .5%

Total Support $17,670,689 100%

Expenditures

Research Grants $15,862,809 Research & Clinical Support 1,129,433

Total Expenditures $16,992,242

*includes support from The Leona M. and Harry B. Helmsley Charitable Trust


To Our Generous Donors and Volunteers...The Diabetes Research Institute and Foundation wishes to gratefullyacknowledge all of our donors and volunteers who are enabling usto make great strides toward a biological cure for diabetes.

Your generous contributions and tireless efforts make the DRI's progress possible.

Thank you to every individual, family, foundation and business, many of whom are pictured on the following pages, that have given generously over the last year and throughout theyears. We would not have been able to come this far without you.

MakingProgressPossible


“Your support means the world to the millions of families like mine who have been affected bydiabetes. Over the years, these fundshave helped the scientists get closerto finding a cure.”

– Renee Aronin (center)

“In total, the Dad's Dayprogram has raised over $40million, which has enabled theDRI to make exciting advancestoward finding a cure for thisdisease that afflicts so manyAmericans.”

– Sean McGarvey, president, North America's Building Trades Unions (right).

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“Walgreens is honored to support the work of the Diabetes Research Institute. We are very grateful to our customers and associates who have been exceptional in supporting the DRI Walk For Diabetes & Family Fun Day, as well as supporting our in-storefundraising program."

– Roy Ripak, Walgreens market vice president (left)

pic 37


“My family and I, are led by my parents, Rowland andSylvia Schaefer, became involvedwith the DRI because we believe the cure for diabetes is within reachand that it will be found by thesescientists."

– Roberta Waller (second from left)

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“Our children are ourinspiration, and we need to find a cure for everyone living with diabetes as quickly as possible.”

– Bonnie Inserra (second from left)

“We had the opportunityto tour the Diabetes ResearchInstitute and we saw what theydo first hand...When we talkabout finding a cure, they are the ones who are in the lab every single day really makingit happen.”

– Ray Allen (second from left)


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“I knew that I wanted to support research for a cure...It’s really a miracle what they’re doing at the Diabetes Research Institute…My advisor was looking out for my best interest and assured me that this was the thing to do. I’m happy that I could establish this gift.”- Frances Harrow

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TheHeritageSociety


The Heritage Society of the Diabetes Research Institute Foundation was created to recognize individuals who have generously made provisions in their wills, through life insurance, charitable remainder trusts and gift annuities, or otherdeferred giving vehicles to ensure that critical funding for the Diabetes ResearchInstitute continues into the future.

Over the years, planned giving programs have enabled many donors to makesubstantial gifts to the DRI in ways that have complemented their individualfinancial objectives. Heritage Society members have chosen to create their ownpersonal legacies and perpetuate their philanthropic goals for all those affected by diabetes.

We are exceptionally grateful to all of our Heritage Society donors who demonstrate the passion and vision to advance a cure beyond their lifetime.

“I am thankful for the life I have lived and truly believethat each of us can make adifference by giving back.”

– Shirley Harris

“Now is the time when we can and must give back and help people.”

– Norman Shapiro

“This will help me rest inpeace knowing that I’ve leftbehind a legacy. I also hope to set an example for mydaughter so that she ischarity-oriented when she is my age.”

– Cindi Elias

“Of all the diabetesorganizations, I chose theDiabetes Research Institutebecause most of the funds go toward what the gift isintended for – a cure.”

– Mark Hariton


NATIONAL BOARDOF DIRECTORS

ChairmanHarold G. Doran, Jr.

Immediate Past ChairmanThomas D. Stern

Vice ChairmenWilliam J. Rand, M.D. Charles Rizzo

TreasurerWilliam J. Fishlinger

SecretaryBonnie Inserra

President and CEOJoshua W. Rednik

DirectorsDiane BeberMarlene BergRonald Maurice Darling, Jr.John C. DoscasPiero GandiniEsther E. GoodmanMarc S. GoodmanArthur HertzGlenn KleimanEleanor KosowSandra Levy Sean McGarvey

Shelia F. Natbony, D.O.Allan L. PashcowRamon PooRicardo SalmonDavid SherrKenneth A. ShewerKathy SimkinsSheldon L. SingerJill VinerBruce WallerSonja Zuckerman

The organization of choice for those who are serious,passionate and committed to curing diabetes.


REGIONAL BOARDSOF DIRECTORS

Florida Region

ChairmanWilliam J. Rand, M.D.*

DirectorsSari AddicottBernard Beber, M.D. Diane Beber* Crystal Blaylock SanchezSabrina R. FerrisBruce FishbeinJoel S. FriedmanRene W. GuimShirley HarrisJavier Holtz Norman Kenyon, M.D. Vito La Forgia Sandra Levy* Ramon Poo* Cristina Poo Deborah Rand

Michelle Robinson Rosa SchechterJames Sensale Jacci Seskin Don Strock Richard P. Tonkinson Stephen Wagman Rita Weinstein Sonja Zuckerman*

Northeast Region

Co-chairsMarc S. GoldfarbBruce A. Siegel

Executive CommitteeWilliam J. Fishlinger*Marc S. Goodman*Barbara HatzBonnie Inserra*

Directors Greg BesnerJohn CarrionDiane CohenDelia DeRiggi-WhittonPeter L. DiCapuaKim DicksteinDouglas R. DonaldsonIris FeldmanJoan FishlingerLindsey Inserra-Hughes John LuebsLouise PashcowHon. C. Raymond RadiganMarie RizzoRicardo Salmon*Samantha Shanken Baker

Meryl LiebermanAllan L. Pashcow*Charles Rizzo*

Thomas P. Silver Bruce Waller*Roberta WallerWendy Waller

*Also member of National Board of Directors


Joshua W. RednikPresident and Chief Executive Officer

Deborah L. ChodrowChief Operating Officer

Jeffrey YoungChief Financial Officer

Tom Karlya Vice President

Jill Shapiro Miller Vice President of Gift Planning

Lori Weintraub, APR Vice President of Marketing and Communications

Lauren Schreier Director of Marketing and Communications

Barbara Singer Director of Special Projects

Karen ParabooAdministration and Database Coordinator

Joelle ParraCommunications and Social Media Coordinator

Melissa PeñaDevelopment Coordinator

Laurie CummingsCommunications Assistant

Aurora Nunez Administrative Assistant

Oneida OsunaAccounting Assistant

Mary Revie Administrative Assistant

Mylinda Auguste Data Entry Clerk

Marisol McKay Date Entry Clerk

Eddy GarciaCourier

Florida RegionSheryl SulkinDirector of Special Events

Nicole Otto Associate Director of Special Events

Dena KaweckiSpecial Events Manager

Sarah MehanSpecial Events Coordinator

Northeast RegionAnthony E. ChildsDirector

Amy Epstein Director of Special Events, Manhattan Office

Lily Scarlett Director of Special Events, Jericho Office

Jill SalterDevelopment Manager

Melinda MegaleSpecial Events Coordinator

Tricia PellizziSpecial Events Coordinator

DRI FOUNDATIONSTAFF


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DiabetesResearch.org

National OfficeFlorida Region 200 South Park RoadSuite 100Hollywood, FL 33021 Telephone 954.964.4040 Toll-free 1.800.321.3437 Fax 954.964.7036

Northeast RegionJericho Office410 Jericho TurnpikeSuite 201Jericho, NY 11753Telephone 516.822.1700Fax 516.822.3570

Manhattan Office381 Park Avenue SouthSuite 1118New York, NY 10016Telephone 212.888.2217Fax 212.888.2219

Diabetes Research Institute Foundation Annual Report 2013

Documents

Transcript of Diabetes Research Institute Foundation Annual Report 2013