PASPCR

August 2013

1

The PASCR Web-Site can be found at:

http://www.paspcr.org

The PASPCR Newsletter is published three times a

year and is intended to serve as a regular means of

communication for the members of our Society. The

PASPCR Newsletter is distributed via e-mail, in pdf

format, on the first of April, August and December and

it will continue to be posted on the web-site of the

Society.

Preparations for 18th

PASPCR Meeting, spear-

headed by Dr. Vijayasaradhi Setaluri, are progressing

well. The meeting will be held in Madison,

Wisconsin, from September 8th to September 11

th, 2013.

Further information on the meeting can be found on

pages 7-11 of this newsletter. In this issue, we continue the “Laboratory Updates”

section with a column by Dr. Gisela Erf. We also

continue the “Industry Perspectives” section with a

column by Dr. Gertrude-Emilia Costin, and the

“Clinical Insights” section with a column by Dr. Reza

Nejati.

We hope you enjoy this issue. We encourage you to

send us your comments at our email address

paspcr.newsletters@gmail.com. Let us know what you

would like to see in the letters, suggest sections you

think would be useful to include, and recommend any

changes that you would like to see.

We also encourage you to let us know about

meetings that you think would be of interest to members

of the Society. If you attend a scientific meeting at

which you heard about work which you think will be of

interest to the membership of the PASPCR, please write

a few paragraphs summarizing what was presented and

share it with us. If you know of training courses that

would be of interest to the PASPCR members, please let

us know and we will add them to a new section in our

Calendar of Events.

Also, keep us updated on any “Members in the

News” so we can spread the word of your successes.

This is your Newsletter, and we depend upon you to

help us ensure it best serves the Society’s needs. We

look forward to hearing your ideas and suggestions and

to continue working together to compile the Newsletters

for our Society.

The PASPCR Newsletter Editorial Team would like

to thank all our contributors for their columns submitted

to us for inclusion in the letters.

PASPCR Newsletter Editorial Team

PASPCR Newsletter August 2013

Vol. 21 Number 2

In this Issue . . . . PASPCR OFFICERS 2

CALENDAR OF EVENTS 2

CORPORATE SPONSORS 3

MEMBERSHIP UPDATES 3

PASPCR PRESIDENT’S CORNER 5

LETTER FROM THE PASPCR SECRETARY/TREASURER 6

18th PASPCR MEETING 7

The Venue 7

Scientific Program 9

Key Dates 11

Sponsors of the Meeting 11

PCMR JOURNAL CORNER 11

PCMR Journal – New Impact Factor 11

MEETINGS ANNOUCEMENTS 12

22nd IPCC 12

HUSCRI SKIN OF COLOR SYMPOSIUM 13

PIGMENTATION COMMUNITY CONNECTIONS 14

LABORATORY UPDATES 15

by Dr. Gisela Erf

INDUSTRY PERSPECTIVES 18

by Dr. Gertrude-Emilia Costin

CLINICAL INSIGHTS 21

by Dr. Reza Nejati

MEMBERS IN THE NEWS 24

PASPCR Members Featured in Yale News, June 26, 2013 24

POSITIONS WANTED/AVAILABLE 24

PASPCR

August 2013

2

C/O Andrzej T. Slominski, M.D., Ph.D.

University of Tennessee Health Science Center

Department of Pathology and Laboratory Medicine

930 Madison Avenue, Room 525 (Clinical Office)

Memphis, TN 38163, U.S.A.

Officers:

Greg Barsh President

Caroline Le Poole President-elect

Andrzej Slominski Secretary/Treasurer

Council Members: Gertrude-Emilia Costin (2012-2014)

Thomas Hornyak (2013-2015)

Lidia Kos (2013-2015)

Deborah Lang (2011-2013)

Sancy Leachman (2012-2014)

John Pawelek (2011-2013)

Glynis Scott (2012-2014)

Vijayasaradhi Setaluri (2011-2013)

Julio Valencia (2013-2015)

IFPCS Representatives:

Andrzej Slominski (Secretary)

Greg Barsh (Council Member)

Frank Meyskens (Council Member)

CALENDAR OF EVENTS

2013

The 18th ESPCR Meeting

Date and place: September 9-12, Lisbon, PORTUGAL

Web-site: http://www.espcr.org/ESPCR2013/

2013

The 18th PASPCR Meeting

Date and place: September 8-11, Madison, WI, USA

Web-site: www.paspcr.org/

2013

HUSCRI Skin of Color Symposium 2013

Date and place: October 25-27, Baltimore, MD, USA

Web-site: http://huscri.org/symposium/

2013

The Annual Meeting of American Society for Cell Biology

Date and place: December 14-18, New Orleans, LA, USA

Web-site: http://www.ascb.org/

2014

The 22nd IPCC

Date and place: September 4-7, Singapore, SINGAPORE

Web-site: http://www.ipcc2014.org/

The PASPCR Newsletter is published three times a year (April, August and December) by the PanAmerican Society for

Pigment Cell Research. All views are those of the authors. For further information or to submit articles, please use the

e-mail address paspcr.newsletters@gmail.com.

Publication Committee

Gertrude-Emilia Costin, Ph.D., M.B.A.

Editor Institute for In Vitro Sciences, Inc. (IIVS)

30 W. Watkins Mill Road #100 Gaithersburg, MD 20878, U.S.A.

(301) 947-6524

ecostin@iivs.org

Prashiela Manga, Ph.D.

Associate Editor New York University School of Medicine

Department of Dermatology

Smilow Research Center 522 First Avenue, Room 401

New York, NY 10016, U.S.A.

(212) 263-9086 prashiela.manga@nyumc.org

William S. Oetting, Ph.D.

University of Minnesota

Department of Medicine - Genetics

MMC 485; 4-12 Moos Tower

515 Delaware Street S.E.

Minneapolis, MN 55455, U.S.A.

(612) 624-1139

oetti001@umn.edu

Andrzej T. Slominski, M.D., Ph.D. University of Tennessee Health Science Center

Department of Pathology and Laboratory Medicine 930 Madison Avenue, Room 525 (Clinical Office)

Memphis, TN 38163, U.S.A.

(901) 448-3741 aslominski@uthsc.edu

The PanAmerican Society for

Pigment Cell Research

PASPCR

August 2013

3

CORPORATE SPONSORS

by Dr. Andrzej Slominski

The PASPCR would like to acknowledge

and thank our Sponsors. The list below reflects

contributions made during the year of 2012. In

the past, financial gifts from our Sponsors have

allowed our Society to increase benefits to the

membership far out of proportion to the actual

dues collected from members. We gratefully

acknowledge the contributions for the 17th

PASPCR Meeting made through PASPCR as

follows (in alphabetical order):

All Resort Transportation

Department of Dermatology at the University

of Utah

Huntsman Cancer Institute at the University

of Utah

Johnson & Johnson Consumer Companies

(Aaron B. Lerner Lecture)

Merck

Morphotek

Myriad Genetics

Prometheus

St. Regis Hotel

- // -

MEMBERSHIP UPDATES

Renewals

Michael G. Anderson

University of Iowa

Iowa City, IA, USA

Raymond E. Boissy

University of Cincinnati

Cincinnati, OH, USA

Sreenivasulu Chintala

Roswell Park Cancer Institute

Buffalo, NY, USA

John A. D'Orazio

University of Kentucky College of Medicine

Lexington, KY, USA

Howard A. Epstein

EMD Chemicals

Philadelphia, PA, USA

David Fisher

Harvard Medical School Boston, MA, USA

Deborah Lang

University of Chicago

Chicago, IL, USA

Julian M. Menter

Morhouse School of Medicine

Atlanta, GA, USA

William J. Pavan

National Institutes of Health Bethesda, MD, USA

Joel Pinczewski

University of Maryland

Owings Mill, MD, USA

Javier Pino

Florida International University

Miami, FL, USA

Archit Trivedi

Toledo, OH, USA

PASPCR

August 2013

4

New Members

Nihal Ahmad

University of Wisconsin Madison, WI, USA

Mark R. Albertini

University of Wisconsin

Madison, WI, USA

Amanda Decker

University of Iowa

Iowa City, IA, USA

Adam M. Hammer

Loyoula University Chicago Maywood, IL, USA

Adam Hedberg-Buenz

University of Iowa

Iowa City, IA, USA

Daniel P. Kestler

University of Tennessee

Knoxville, YN, USA

Himangi Marathe University of Toledo

Toledo, OH, USA

Katsuo Matsumoto

POLA Chemical Industries, Inc. Totsuka-ku

Yokohama, JAPAN

Gaurav Mehta

University of Toledo

Toledo, OH, USA

Tahseem H. Nasti

University of Alabama Birmingham, AL, USA

Amy Saldana

Florida International University

Miami, FL, USA

Hannah Seberg

University of Iowa

Iowa City, IA, USA

Laura Timares

University of Alabama Birmingham, AL, USA

Xiaoqi Wang

Northwestern University Feinberg School of

Medicine

Chicago, IL, USA

Maria L. Wei

UCSF San Francisco, CA, USA

Sunghan Yim

Avon Products, Inc.

Suffern, NY, USA

Update

Sancy Leachman

New E-mail Address: leachmas@ohsu.edu

- // -

PASPCR

August 2013

5

PASPCR PRESIDENT’S CORNER

We are still a few months away from

Autumn, but I find myself feeling somewhat

autumnal, in part because my term as PASPCR

President will finish this year, in part because

the continued sorry state of US science funding

heralds a very cold spell for important advances

in basic research, and in part because of my own

midlife, er, catharsis.

Helping to lead PASPCR has been terrific,

but I wish I could do more. Like other scientific

societies, we continue to face a diversity of

challenges, yet manage to hang on as a

community of colleagues with shared interests,

and, often, as friends. I continue to believe that

for our Society to flourish (perhaps even to

survive), we must identify areas that will attract

and excite young scientists, consider new ways

of communicating that are not tied to publishing

companies, and look to our sister Societies for

alliances that offer synergy and strength.

Perhaps these issues can be discussed informally

next month in Madison, in ways that will

energize and invigorate, and maybe even

expand, our group and our comfort zones.

Of course, the biggest challenge we face is

the increasingly grim outlook for NIH funding.

Caught in a perfect storm of a national economy

that is still stumbling, NIH priorities that

threaten individual investigators funded by RO1

grants, and a political landscape poisoned by

bickering and ignorance, it’s hard to stay

optimistic. One bright spot is the Society itself -

speaking with many of you by phone or by email

over the last several months, I sense the same

curiosity, critical thinking, and fascination with

biology that characterized the Pigment Cell

Societies at their inception, and that continues, I

think, to motivate all of us. Another bright spot,

for me at least, is genomics. The same

technological advances that feed “big biology”

can, perhaps ironically, be applied to systems

and questions that were previously inaccessible.

I’m reminded of a quote from Sydney Brenner:

“Progress in science depends on new techniques,

new discoveries, and new ideas, probably in that

order”. Ideas may be our currency, but their

value depends heavily on implementation, and I,

for one, continue to be amazed at the ways in

which genomic technology can be applied to

new questions.

What about that midlife crisis? While other

middle aged pigment cell biologists have ended

up in small sports cars, I decided to get a big

telephoto lens, which was put to good use after

the IFPCS Special Interest Developmental

Biology Meeting earlier this year. Ian Jackson

and Liz Patton organized a wonderful 3 days of

science and science friends, and did so in the

amazing city of Edinburgh. It was my first real

visit to Scotland, and I took full advantage of the

opportunity to spend an extra 3 or 4 days

wandering through the Scottish Highlands.

There was a bit of whisky tasting, but I spent

most of my time in search of warm-blooded

pigmentary diversity apparent in Atlantic

Puffins, Northern Gannets, and, a spectacular

King Eider, courtesy of an insider

recommendation from Robert Kelsh. The only

thing more exciting than seeing these animals in

their natural environment is the opportunity to

capture and share their images, which I hope to

do with many of you this Fall in Madison.

Greg Barsh, M.D., Ph.D.

PASPCR President

- // -

PASPCR

August 2013

6

LETTER FROM THE PASPCR

SECRETARY/TREASURER

Dear PASPCR members,

The date of the XVIIIth

PASPCR meeting

in Madison, Wisconsin (see

http://www.paspcr.org/paspcr2013/index.php) is

approaching very fast and I urge all members of

the PASPCR or investigators interested in the

pigment cell biology to attend this meeting.

Those who want to present their latest work can

still submit it as a late breaking abstract till

August 15, 2013. The Organizing Committee

under the leadership of Dr. Vijayasaradhi

Setaluri has prepared an outstanding scientific

program that is well balanced and focusses on

the Advances in Melanocyte and Melanoma

Biology. It is marked by excellent speakers

invited by the organizers, and is supplemented

by excellent oral presentations selected from the

submitted abstracts. Of note is the Key Note

lecture by Dr. Hector DeLuca entitled “The

Vitamin D Story, From Basic Science to the

Clinic”. Dr. DeLuca is a distinguished

investigator, member of the National Academy

of Science, USA and recipient of many awards

who built the foundations for modern research

on vitamin D and its clinical application.

Vitamin D is an extremely important molecule

that, in addition to regulating calcium body

homeostasis, expresses several other

bioregulatory functions both on systemic and

local (skin) levels. Here I would like to add that

during the PASPCR meeting in Memphis, Dr.

Holick, a trainee of Dr. DeLuca, also presented

on vitamin D and its crucial role in physiology.

Furthermore, Dr. David E. Fisher, Chairman

of the Department of Dermatology, MGH,

Harvard Medical School, will present the Aaron

B. Lerner Lecture entitled “From MITF to

Redheads and Associated Phenotypes”. Dr.

Fisher is a member of our Society in good

standing and we cherish his membership in the

PASPCR.

Importantly, having residual funds raised for

the PASPCR meeting in Memphis we are

planning to grant 16-17 travel grants in the

amount of $500 per award. These will be

distributed predominantly to postdocs and

students to attend the PASPCR meeting in

Madison, WI. The awards will be based on the

eligibility and scientific soundness of the

abstracts as determined by the Scientific

Committees. To be eligible, the recipient has to

be a member of the PASPCR, be first and

presenting author and the priority will be given

to students and postdoctoral fellows.

During the meeting a new

Secretary/Treasurer will be selected, since the

current Secretary/Treasurer is serving the sixth

year on this position, a maximum allowed by the

PASPCR bylaws. However, Dr. Slominski will

continue to serve as Council member for next 2

years (2014-2015), and will represent our

Society as the Secretary of the IFPCS till the end

of 2014.

We are also acknowledging the support of

Johnson and Johnson ($5,000) to cover the costs

connected with Aaron B. Lerner lecture. We also

acknowledge the sponsorship of the Conference

by Merck ($2,500), Janssen ($1,500) and

Daavlin ($1,000).

We hope that you will be able to attend this

meeting, which will not only cover many aspects

of pigment cell biology from basic to clinical

science, but also other areas of life science such

as role of vitamin D in biomedical research and

medicine. Therefore, please mark your calendar

for September 8-11, 2013 to attend the XVIIIth

PASPCR meeting in Madison, Wisconsin.

I also provide some statistics on the

membership. The total number of current

members in good standing is 123, which

includes 31 student members, 2 members of

Japanese and 2 members of the European

Society, and 5 members of the SMR.

Thank you again for your support of our

Society and I am looking forward to see you in

Madison!

Andrzej Slominski, MD, PhD

Professor of Pathology and Medicine

Secretary/Treasurer of the PASCPR and

Secretary of the IFPCS

PASPCR

August 2013

7

18th

PASPCR MEETING

September 8th

– September 11th

, 2013, MADISON, WI, USA

PASPCR

August 2013

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PASPCR

August 2013

9

Scientific Program

Sunday, September 8, 2013

6:00pm – 9:00pm Reception & Registration

Monday, September 9, 2013

8:00am – 8:30am Breakfast

8:30am – 8:45am Welcome and opening remarks

Drs. Vijay Setaluri and Greg Barsh

8:45am – 8:50am Introduction of Keynote Speaker

Dr. Gary Wood

8:50am – 9:50am Keynote Lecture: The Vitamin D Story, From Basic Science to the Clinic Dr. Hector F. DeLuca, University of Wisconsin, Madison

9:50am – 10:00am Break

10:00am – 12:30pm Plenary Session I: Melanocyte Development & Melanoma Cancer Stem

Cells

10:00am – 10:30am Invited Lecture: Neurofibromin Gene Dosage and Melanocyte Development

Dr. Catherine Van Raamsdonk, University of British Columbia, Vancouver,

British Columbia, Canada

10:30am – 11:00am Invited Lecture: Phenotypic Heterogeneity in Tumorigenic Melanoma Cells

Dr. Elsa Quintana, OncoMed Pharmaceuticals, Redwood City, CA

11:00am – 11:45am Oral session 1: Melanocyte development

(3 talks from selected abstracts, 12 min plus 3 min discussion)

11:45am – 12:30pm Oral session 2: Melanoma tumor initiating cells

(3 talks from selected abstracts, 12 min plus 3 min discussion)

12:30pm – 1:30pm Lunch

1:30pm – 2:30pm Poster Session I

2:30pm – 5:15pm Plenary Session II: Melanocyte UV Response and Mouse Melanoma

Models

2:30pm – 3:00pm Invited Lecture: MC1R and Melanocyte Response to UV

Dr. Zalfa Abdel-Malek, University of Cincinnati, Cincinnati, OH

3:00pm – 3:30pm Invited Lecture: Genetic Mouse Models of Pigmentation and Melanoma

Dr. Marcus Bosenberg, Yale University, New Haven, CT

3:30pm – 3:45pm Break

3:45pm – 4:30pm Oral session 3: UV and skin pigmentation

(3 talks from selected abstracts, 12 min plus 3 min discussion)

4:30pm – 5:15pm Oral session 4: Animal models

(3 talks from selected abstracts, 12 min plus 3 min discussion)

PASPCR

August 2013

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5:15pm – 6:15pm Poster session II with wine & cheese

Tuesday, September 10, 2013

8:00am – 9:00am Breakfast with experts: Opportunities and Challenges in Pigment Cell Research

A Q&A session for aspiring graduate students and postdocs

9:00am – 11:45am Plenary Session III: Cell & Molecular Biology of Normal & Malignant

Melanocytes

9:00am – 9:30am Invited Lecture: Fly Eye Pigmentation and Human Disease

Dr. Esteban Dell'Angelica, University of California, Los Angeles

9:30am – 10:00am Invited Lecture: ATF2, At the Crossroad of Nuclear and Cytosolic Functions

Dr. Ze'ev Ronai, Sanford-Burnham Medical Research Institute, La Jolla, CA

10:00am – 10:15am Break

10:15am – 11:00am Oral session 5: Biology of melanin pigmentation

(3 talks from selected abstracts, 12 min plus 3 min discussion)

11:00am – 11:45am Oral session 6: Biology of malignant melanocytes

(3 talks from selected abstracts, 12 min plus 3 min discussion)

11:45am – 12:30pm Poster session III

12:30pm – 1:30pm Lunch

1:30pm – 2:30pm Aaron Lerner Award Lecture: From MITF to Redheads and Associated

Phenotypes Dr. David Fisher, Harvard Medical School, Boston, MA

2:30pm – 5:15pm Plenary Session IV: Immune Responses to Normal & Malignant

Melanocyte

2:30pm – 3:00pm Invited Lecture: Dissection of T Cell Responses in Vitiligo

Dr. José A. Guevara-Patiño, Loyola University Medical Center, Chicago, IL

3:00pm – 3:30pm Invited Lecture: Genetics of Vitiligo

Dr. Richard Spritz, University of Colorado, Denver

3:30pm – 3:45pm Break

3:45pm – 4:30pm Oral session 7: Pathobiology of vitiligo

(3 talks from selected abstracts, 12 min plus 3 min discussion)

4:30pm – 5:15pm Oral session 8: Melanocyte antigens in melanoma immune response

(3 talks from selected abstracts, 12 min plus 3 min discussion)

5:15pm – 6:00pm Poster session IV

6:30pm Gala Dinner

PASPCR

August 2013

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Wednesday, September 11, 2013

8:00am – 9:00am Breakfast with experts: Opportunities and Challenges in Pigment Cell &

Melanoma Research

A Q&A session for aspiring graduate students and postdocs

9:00am – 11:45am Plenary Session V: Bench-to-Bedside & Back

9:00am – 9:30am Invited Lecture: Melanoma Next-generation Sequencing, Biological

Significance and Clinical Applications

Dr. Ruth Halaban, Yale University School of Medicine, New Haven, CT

9:30am – 10:00am Invited Lecture: Survival in BRAF V600-mutant Advanced Melanoma Patients

Dr. Jeff Sosman, Vanderbilt-Ingram Cancer Center, Nashville, TN

10:00am – 10:15am Break

10:15am – 11:00am Oral session 9: Malignant transformation of melanocytes

(3 talks from selected abstracts, 12 min plus 3 min discussion)

11:00am – 11:45am Oral session 10: Drug resistance of melanoma

(3 talks from selected abstracts, 12 min plus 3 min discussion)

11:45am – 1:00pm Poster session V

1:00pm – 2:00pm Lunch & Departure

Key Dates

Early Registration Rates extended until August 15th

, 2013

Late Breaking Abstracts for Poster Session only can be submitted until August 15th

, 2013

Sponsors of the Meeting

Johnson & Johnson

Merck

Janssen

Daavlin

Nikon

- // -

PCMR JOURNAL CORNER

The PCMR Journal announced in July its new Impact Factor of PCMR: 5.839!

The journal is growing and thriving thanks to an amazing professional commitment of its editors,

reviewers and authors to constantly improve and develop the journal.

PASPCR

August 2013

12

22ND

INTERNATIONAL PIGMENT CELL CONFERENCE

September 4th

– September 7th

, 2014, SINGAPORE

The 22nd

International Pigment Cell Conference (IPCC) will be held from 4th

to 7th

September

2014 in Asia’s top convention city, Singapore. Hosted by the Asian Society for Pigment Cell Research

(ASPCR), in partnership with the Dermatological Society of Singapore (DSS), this triennial meeting of

the International Federation of Pigment Cell Societies will be held in conjunction with the 27th

Annual

Scientific Meeting of the DSS.

IPCC 2014 has been themed “Bringing Colours to Life” as it aims to capture the vibrant

advancements in pigment cell research and their applications in dermatology and clinical medicine.

Distinguished researchers, clinicians as well as young investigators will be sharing the leading

advances in basic and translational research in pigment cell biology and melanoma, and address the

burden of pigmentary disorders across Asia. The organizers believe that this important event offers an

excellent opportunity for the exchange of ideas among clinicians and scientists and fosters international

collaboration.

Apart from offering you an outstanding scientific program, the organizers invite the participants

to experience Singapore, a bustling cosmopolitan city-state with a unique blend of modernity and

traditional charm. Home to a vibrant, multi-cultural society and a multitude of award-winning

attractions, this beautiful city will undoubtedly enrich your overall experience.

Organizers:

Dr. Boon-Kee Goh, Organizing President - IPCC 2014

Dr. Su-Ni Wong, President - Dermatological Society of Singapore

Dr. Mauro Picardo, President - International Federation of Pigment Cell Societies

PASPCR

August 2013

13

2013 SKIN OF COLOR SYMPOSIUM

October 25th

– October 27th

, 2013, BALTIMORE, MD, USA

The 2013 Skin of Color Symposium will be held October 25-27, 2013 in Baltimore’s charming and

dynamic Inner Harbor at the Royal Sonesta Harbor Court Hotel. The symposium is designed for

dermatologists, plastic surgeons, primary care physicians, physician assistants, residents, students and

professionals with an interest in skin research in skin of color. The objectives of the symposium are to

identify, diagnose and treat rare or serious dermatological diseases that are more prevalent in skin of

color and to translate research about dermatological diseases that are most commonly seen in skin of

color and to apply those findings to clinical practice.

This activity has been planned and implemented in accordance with the Essential Areas and

policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint

supportership of Eastern Virginia Medical School and Hampton University’s Skin of Color Research

Institute. Eastern Virginia School is accredited by the ACCME to provide continuing medical

education for physicians. Eastern Virginia Medical School designates this activity for a maximum of

11.5 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the

extent of their participation in the activity.

For more information on the meeting, visit www.huscri.org/symposium.

Dear Colleague,

You are invited to submit abstracts for the Skin of Color Symposium 2013.

The meeting will be held October 25-27, 2013 in Baltimore's charming and dynamic Inner Harbor at the Royal Sonesta Harbor Court Hotel.

Abstract submission opens July 1, 2013.

All abstracts MUST BE SUBMITTED ONLINE VIA THE

HUSCRI ABSTRACTS SUBMISSION SITE

(http://huscri.org/symposium/abstract-submission.php).

Important Notice

The following abstract submission policies will be firmly enforced:

No Previously Published Submissions

The abstract submitted must present original work that has not and will not be

published or presented prior to the 2013 HUSCRI meeting.

No Dual Submissions

The abstract must not have been submitted to any other upcoming meeting.

No Previously Presented Data

All abstracts must be new and original content OR include at least 50% new data if previously presented at a meeting.

For more information, visit www.huscri.org/symposium.

PASPCR

August 2013

14

PIGMENTATION COMMUNITY CONNECTIONS

Courtesy: http://www.mygeo.info/karten/802784.jpg

Patient/

ConsumerResearch

Industry Academia

Regulatory bodies

Medicine

Final products

In this issue, we continue the “Laboratory

Updates” with a column by Dr. Gisela Erf, the

“Industry Perspectives” with a column by Dr.

Gertrude-Emilia Costin, and the “Clinical

Insights” with a column by Dr. Reza Nejati. We

hope that you will be inspired to take the

opportunity to fill us in on what is happening in

your lab or company. Volunteers would be greatly

appreciated, just email us at

paspcr.newsletters@gmail.com.

This initiative is part of our effort to keep the

Pigmentation community connected and to

emphasize the importance of collaboration and

communication between groups. We will keep

adding stars on our world map below each time

you contribute a column about your newest

research projects. So, let’s go on a global research

adventure!

PASPCR

August 2013

15

LABORATORY UPDATES

by Dr. Gisela Erf

The study of spontaneous autoimmune

vitiligo in the Smyth line (SL) chicken model

(Figure 1) has been part of my research program

for 24 years; initially in collaboration with Dr. J.

Robert Smyth, Jr. during my tenure as Assistant

Professor at Smith College, Northampton, MA

and, since 1994, as PI at the University of

Arkansas, Division of Agriculture, in

Fayetteville, AR. At the time I started working on

SL vitiligo, Dr. Smyth and collaborators already

had strong evidence of a role of the immune

system in the post-natal loss of SL melanocytes

(Smyth, 1989). Collectively, research in our avian

immunology laboratory established the

autoimmune nature of SL vitiligo and further

demonstrated the many biological and clinical

similarities between SL and human vitiligo (Erf

et al., 1995, 1997; Erf and Smyth, 1996; Shresta

et al., 1997; Wang and Erf, 2003, 2004; Wick et

al., 2006; Erf, 2010, 2013).

Like other autoimmune diseases, autoimmune

vitiligo in SL chickens is multifactorial in nature

requiring interplay of genetic, immune system

and environmental components for expression.

Genetic susceptibility to SL vitiligo appears to be

manifested in part by inherent defects or

“weaknesses” in the pigmentation system,

predisposing melanocytes to immunorecognition.

Additionally, genetic susceptibility may include

aberrant immunological activity at various levels.

Genetic susceptibility alone, however, does not

appear to be sufficient for SL vitiligo expression.

Rather, post-natal development of vitiligo in

susceptible SL chickens appears to be dependent

on environmental triggers. We identified routine

herpesvirus of turkey (HVT) administration (live

virus vaccination) at hatch as one environmental

factor that reliably triggers vitiligo expression in

susceptible SL chickens (Erf et al., 2001). With

live HVT administration at hatch, 80-95% of SL

hatch-mates will develop vitiligo between 6 and

20 weeks of age, whereas without HVT and in

defined housing conditions, the incidence of SL

vitiligo is reduced to nearly 10%. Lastly, as is the

case in human autoimmune vitiligo and other

autoimmune diseases, SLV can be accompanied

by other autoimmune/inflammatory diseases,

most notably autoimmune thyroiditis (Smyth,

1989).

Figure 1. Post-natal development of

autoimmune vitiligo in Smyth line chickens Top: One-day-old Smyth line chick (top left) and

6-week-old male and female Smyth line chickens

(right) prior to vitiligo onset.

Middle: Adolescent (12-week-old) SL chickens

with varying degrees of vitiligo (left); young

adult Smyth line hen without vitiligo (right).

Bottom: growing feathers with varying degrees of

pigmentation loss.

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Other characteristics of this animal model that

make it particularly suitable to study the etiology

and pathology of vitiligo is the location of, and

the continual access to, the autoimmune lesion. In

birds, melanocytes are present in the bottom 3-4

mm newest growth of growing feathers where

they are arranged around a column of inner pulp

(dermis-like tissue) within an epidermal layer of

keratinocytes. Growing feathers can be easily

removed for analysis from the same individual at

various times before and throughout development

and progression of SLV (Figure 1, bottom) and

the target tissue can be manipulated by

microinjection of test-materials (Erf et al., 1995,

Shi and Erf, 2012; Shi et al., 2012).

We currently maintain three lines of chickens

that constitute the model system for our research:

The Smyth line (SL), the Brown line (BL), and

the Light-brown Leghorn (LBL), all of which

have similar plumage pigmentation patterns and

are MHC-matched (B101/101

). As stated above,

under conventional rearing conditions, 80-95% of

SL chicks will develop vitiligo (SLV) between 6

and 20 weeks of age. Hence, SL chickens are

considered vitiligo susceptible with high vitiligo

expression. The BL is the parental line from

which the SL was originally derived (Smyth et

al., 1981; Smyth, 1989). While vitiligo

expression in the BL is rarely observed, BL

chickens are never-the-less considered vitiligo-

susceptible based on a 71% incidence of vitiligo

when treated with the DNA-methylation inhibitor

5-Aza-cytidine (Sreekumar et al., 1996). The

LBL chicken has no incidence of vitiligo and

does not develop vitiligo with 5-Aza-cytydine

treatment, hence the LBL line is considered

vitiligo resistant. Additionally, SL that carry a

sex-linked homozygous recessive dermal

pigmentation gene (id/id-male, id-female) that

results in grey/green pigmentation of the shanks

(SL-GS) generally do not express SL vitiligo.

With the complex, multifactorial nature of SL

autoimmune vitiligo, ongoing research in our

laboratory is also multifaceted. The genetic

susceptibility to SL vitiligo is being addressed

through two collaborations. Quantitative trait

analysis continues to be conducted by Drs. S.

Kerje and L. Andersson at Uppsala University in

Sweden. Whole genome sequencing comparing

SL, SL-GS, BL and LBL to the Red Jungle Fowl

reference chicken genome is being conducted by

my colleague Dr. B-W Kong, Department of

Poultry Science, University of Arkansas.

Preliminary findings based on genome re-

sequencing of SL and BL DNA revealed various

potential genetic markers with amino acid

changes and potential roles in vitiligo

development.

While examining in vitro and in vivo effects

of 4-TBP, a phenolic compound associated with

vitiligo development in humans, Ph.D. student

Lei Dong observed highly divergent responses of

SL melanocytes compared to SL-GS-, BL- and

LBL-control melanocytes. Aspects examined

included oxidative radical production,

pigmentation-, apoptosis- and stress-related gene-

expression, and melanocyte morphology.

Findings from this study not only demonstrated

altered ability of SL melanocytes to cope with

cellular stress, but also provided us with a system

to reveal “inherent weaknesses” in the

pigmentation system that may predispose SL

chickens to vitiligo development. We are in the

process of developing research collaborations

with Dr. Prashiela Manga’s research group at

New York University School of Medicine, New

York, NY, to further examine cellular responses

of avian and human melanocytes.

Making use of the opportunity to monitor the

developing autoimmune lesion, we continue to

investigate immune system activities leading to

autoimmune loss of melanocytes. Targeted and

global gene-expression analysis at the

transcriptome level throughout SL vitiligo

expression revealed a unique cytokine signature

with concomitant increases of IFN-γ, IL-10 and,

most prominently, IL-21 and IL-21receptor

expression (Shi and Erf, 2012; Shi et al., 2012).

Current research by Ph.D. students Kristen Byrne

and Daniel Falcon focus on identifying key

immunological components (innate and adaptive

immunity, respectively) and activities that drive

and mediate the loss of melanocytes in

susceptible SL chickens.

The environmental trigger of SLV expression

in the form of HVT continues to be another focus

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of our research group. Recently, we identified a

window in time when this virus can influence

SLV expression. Administration of HVT within

the first 2 weeks of life was found most effective

in triggering SLV expression. However, the

incidence of SLV dropped to 35% when HVT

was administered at 6 weeks. SLV did not

develop when HVT was administered at 10

weeks of age (the next time point tested) or later.

The observation of the age-dependent

ability/inability of HVT to trigger vitiligo

expression in susceptible SL chickens provides

unique opportunities to examine the interplay

between genetic susceptibility and environmental

triggers in autoimmune disease expression. We

are hoping to find collaborators who would be

interested in pursuing this important research

question.

Several studies are also underway by

undergraduate researchers in our laboratory.

Amir Mortazavi is examining qualitative and

quantitative aspects of melanocyte-specific

autoantibodies in a time course study starting

when the chicks were 2 weeks of age until SLV

had fully developed. Jordan Sorrick and Wilson

Huett are examining immune activities in the

choroids of SL with apparently normal sight,

partial blindness or complete blindness. Immune

system activities (cell infiltration, cytokine and

chemokine expression) associated with loss of

choroidal melanocytes and development of

blindness appear to be strikingly similar to

activities observed in the autoimmune lesion in

growing feathers.

We’ll continue to maintain this animal model

and to conduct research in this area; however,

with other commitments and limited funding,

research progress is slow and many aspects of

this project extend beyond our area of expertise.

Hopefully this update will initiate discussion on

collaborative studies and the valuable

contribution this avian model can make to our

understanding, prevention and treatment of

multifactorial, non-communicable diseases such

as autoimmune vitiligo.

References:

Wick, G., L. Andersson, K. Hala, M. E. Gershwin, C. F.

Selmi, G. F. Erf, S. J. Lamont, and R. Sgonc. 2006.

Avian models with spontaneous autoimmune diseases.

Adv. Immunol. 92:71-117.

Erf, G. F. 2010. Animal models. Pages 205-218 in: Vitiligo,

Picardo, M and A. Taieb, editors. Springer-Verlag

GmbH, Berlin Heidelberg, Germany.

Erf, G. F. 2013. Autoimmune diseases of poultry. Avian

Immunology, 2nd

edition. Davison F., Kaspers B., and

K. Schat, editors. Elsevier, Oxford, UK (in press)

Erf, G. F., and J. R. Smyth, Jr. 1996. Alterations in blood

leukocyte populations in Smyth Line chickens with

autoimmune vitiligo. Poult. Sci. 75:351-356.

Erf, G. F., A. V. Trejo-Skalli, and J. R. Smyth, Jr. 1995. T

cells in regenerating feathers of Smyth line chickens

with vitiligo. Clin. Immunol. Immunopathol. 76:120-

126.

Erf, G. F., A. V. Trejo-Skalli, M. Poulin, and J. R. Smyth,

Jr. 1997. Dermal lymphoid aggregates in autoimmune

Smyth line chickens. Vet. Immun. Immunopathol.

58:335-343.

Erf, G. F., T. K. Bersi, X. Wang, G. P. Sreekumar, and J. R.

Smyth, Jr. 2001. Herpesvirus connection in the

expression of autoimmune vitiligo in Smyth line

chickens. Pigment Cell Res. 14:40-46.

Shi, F., and G. F. Erf. 2012. IFN-gamma, IL-21 and IL-10

co-expression in evolving autoimmune vitiligo lesions

of Smyth line chickens. J. Invest. Dermatol. 132:642-

649.

Shi, F., B.-W. Kong, J. J. Song, J. Y. Lee, R. L.

Dienglewicz, and G. F. Erf. 2012. Understanding

mechanisms of spontaneous autoimmune vitiligo

development in the Smyth line chicken model by

transcriptomic microarray analysis of evolving lesions.

BMC Immunology 13:18; 1-15.

Shresta, S., J. R. Smyth, Jr., and G. F. Erf. 1997. Profiles of

pulp infiltrating lymphocytes at various times

throughout feather regeneration in Smyth line chickens

with vitiligo. Autoimmunity 25:193-201.

Smyth, J. R. Jr., R. E. Boissy, and K. V. Fite. 1981. The

DAM chicken: a model for spontaneous postnatal

cutaneous and ocular amelanosis. J. Hered. 72, 150-156.

Smyth, J.R. Jr. (1989). The Smyth chicken: a model for

autoimmune amelanosis. Poult. Biol. 2, 1-19.

Sreekumar, G. P., G. F. Erf, and J. R. Smyth, Jr. 1996. 5-

Azacytidine treatment induces autoimmune vitiligo in

the parental control strains of the Smyth line chicken

model for autoimmune vitiligo. Clin. Immunol.

Immunopathol. 81:136-144.

Wang, X., and G. F. Erf. 2003. Melanocyte-specific cell

mediated immune response in vitiliginous Smyth line

chickens. J. Autoimmun. 21:149-160.

Wang X., and G. F. Erf. 2004. Apoptosis in feathers of

Smyth line chickens with autoimmune vitiligo. J.

Autoimmun. 22: 21-30.

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August 2013

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Contact:

Gisela F. Erf, Ph.D. Tyson Professor in Avian Immunology

University of Arkansas

Center of Excellence for Poultry Science O-410

1260 W. Maple Street

Fayetteville, AR 72701, USA

Phone: (479-575-8664

Fax: 479-575-7139

Email: gferf@uark.edu

- // -

INDUSTRY PERSPECTIVES

by Dr. Gertrude-Emilia Costin

Colors and nuances of transitions in science.

How I remained faithful to the field of

pigmentation…

I was thinking the other day that our journey

in life (and our evolution in science as scientists)

is a series of transformations/transitions. Being a

biochemist by training, I was looking at my

“transitions” from the perspective of a molecule

that goes so often from its T (tense) state to the R

(relaxed) state based on numerous molecular

interactions that occur within the cellular

environment. Likewise, we are many times facing

numerous transitions and have to find our best

way to interact with others, with the fast-paced

changes in science and somehow, if possible,

remain close to a field if that is what makes us

comfortable and at ease as researchers. I realized

over the years that remaining faithful to the field

of pigmentation offered me the strength to

transition better when needed. Here is my journey

that I would like to share with you.

My first research project having to deal with

pigmentation started with my first job as assistant

researcher at the Institute of Biochemistry of the

Romanian Academy in Bucharest, Romania. One

of the ongoing projects in the Glycobiology

Laboratory led by the Director of the Institute,

Dr. Stefana Petrescu, investigated the folding and

maturation of tyrosinase, the enzyme that

regulates the melanin production in mammals.

One of the compounds used in their research was

the glycosylation inhibitor N-

butyldeoxynojirimycin (NB-DNJ). The studies of

the team led by Dr. Petrescu showed that this

small molecule interfered with the folding and

maturation of tyrosinase and completely

abolished the enzymatic activity of tyrosinase

resulting in the complete loss of melanin

production in B16F1 mouse melanoma cells (1).

While learning from my mentor, Dr. Mihaela

Trif, about intracellular trafficking using

liposomes I started to use those vehicles for a

more efficient way to transport NB-DNJ into

mouse melanoma cells (B16F1). Thus, my Ph.D.

project showed that pH-sensitive liposomes were

efficient carriers for the delivery of imino-sugars

such as NB-DNJ to the endoplasmic reticulum of

mammalian cells (2, 3). While the system based

on B16F1 cells was initially designed as a

working model for the later investigated

trafficking of hepatitis B (4, 5), I soon became

interested in gaining a better understanding of

how melanin production can be modulated in

various ways by agents that could eventually be

used in cosmetic formulations or drugs. Luckily,

the occasion arose when I had been offered the

opportunity to become part of Dr. Vincent

Hearing’s lab at National Institutes of Health

(NIH), in Bethesda, MD, USA. That was my first

transition as scientist.

In many ways, the skills acquired during my

Ph.D. training advanced while in Vince’s lab.

However, I felt farther apart from my original

basic training as biochemist and it looked like I

was more of a cellular and molecular biologist. It

was then when I felt that I transitioned slowly but

still kept alive my interest in skin color

modulation and the fascination with color in

general. While at NIH, I was involved in several

very interesting projects that fulfilled in some

ways my interest in modulation of melanin

production at the cellular and molecular level.

One of my projects investigated oculocutaneous

albinism type 4 (OCA4), a (then) newly

identified human autosomal recessive

hypopigmentary disorder of skin, hair, and eyes.

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Our data showed that tyrosinase was abnormally

secreted within immature melanosomes from

primary melanocytes I had derived from mice

that carry the underwhite (uw) mutation

(provided by Dr. Lynn Lamoreux, Texas A&M

University, College Station, TX, USA) which

affects the membrane-associated transporter

protein (MATP) (6).

A secondary project was based on

melanocytes that carry the slaty and slaty light

mutations in the gene for dopachrome

tautomerase (dct), an enzyme that is pivotal in

the biosynthesis of melanin and in the rapid

metabolism of its toxic intermediates. This

project actually started as a “hobby” as I tried to

improve my cell culture skills, knowing that these

melanocytes were more difficult to grow being

more sensitive due to their mutations. We

published a first set of results showing the culture

of immortalized lines (7) and then used them

further for a more ample project that showed that

the slaty and slaty light mutations affect the

eumelanin/pheomelanin synthesis but not the

intracellular trafficking of the mutant proteins (8).

While attending PanAmerican Society for

Pigment Cell Research (PASPCR) meetings I had

the opportunity to meet Dr. Gopinathan Menon

(currently at ISP Corporation) who introduced me

to Avon Products Global R&D (Suffern, NY,

USA) where I started to work in 2005 as senior

research scientist shortly after concluding my

post-doctoral training at NIH. I lived through that

transition with eyes wide open as the industry

language was much different from what I was

used to and as the interests of my group were skin

care at large and not exclusively focused only on

pigmentation. I admit that while I have learned a

lot about skin, skin care, consumer expectations

from cosmetic products in general, etc. I still

managed to use my pigmentation background

since melanin production is a special skin trait.

As you have already understood, that was my

second scientific transition. And it was the one

that brought me closer to answering the questions

I left Bucharest with years before: how can basic

knowledge be applied to create products that

modulate melanin production on the basis of the

novelty and efficacy of their ingredients? While

my tenure at Avon Products was unfortunately

relatively short, it stimulated me to publish a

successful review manuscript entitled “Human

skin pigmentation: melanocytes modulate skin

color in response to stress” and co-authored with

Vince Hearing (9). To my big surprise even to

this day, this review manuscript that compiled the

best of my knowledge in pigmentation at that

time is still ranking first among the most

frequently read papers after six years or more

after its publication in FASEB Journal (10).

Needless to say, I am very proud to have co-

authored a manuscript that is of such steady and

high interest in the field.

My third scientific transition took place in

2007 with the move to the Institute for In Vitro

Sciences, Inc. (IIVS) (Gaithersburg, MD, USA)

where I have worked as Study Director and

Toxicologist since. At first I felt uneasy to be

called a toxicologist as I have always been “a

biochemist in transition” and cellular/molecular

biologist at most. To this day I struggle with that

title as I came to realize that I have not followed

the classical training of a toxicologist in the

United States. I am rather a toxicologist by

training at work rather than in school. Which at

times can be an excellent route to gain

experience.

I have recently attended the introductory

lecture presented by Dr. Wallace Hayes as part of

the Toxicology for Industrial and Regulatory

Scientists Course organized by the American

College of Toxicology. The presenter asked the

audience to raise hands if any of us were

toxicologists. I believe it was the first time in the

last six years of working as a toxicologist when I

felt almost fully comfortable to claim that

position. And that is because I learned a lot and

came to realize that I do that every day

continuously, by reading, attending meetings,

conferences, discussing with our clients and

collaborators, etc. My happiness was cut short

soon thereafter while realizing during the course

that the general concept is that “the toxicologist”

is that scientist who has a wide background

pertaining to in vivo studies. That made me

realize that the in vitro toxicology field I’m in

right now is catching up but it also has a lot of

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convincing to do when it comes to replacing the

animal work with cell- or tissue-based assays.

And that is IIVS’s mission by promoting in vitro

assays as a replacement of animal

experimentation whenever possible, particularly

for the safety assessment of cosmetic and

personal care products and based on the strict

regulations currently enforced by the European

Union.

At IIVS I am the Study Director for a wide

array of in vitro assays focused on safety

assessment of various types of products

(cosmetic, household, pharmaceuticals,

pesticides, etc.). While my primary responsibility

is geared towards dermal safety, my knowledge

expanded quickly to assays using in vitro ocular,

mucosal testing platforms (11-13). IIVS has the

status of a Contract Research Organization

(CRO) and therefore the commercial studies

performed at IIVS came with the mandatory

training in Good Laboratory Practices (GLPs).

Well, that was scary at first as I was not familiar

with GLPs when I started but I can currently state

that acquiring this knowledge was a rewarding

and useful experience. I was supported by and

have benefited fully from the experience of all

my coworkers, especially our Vice-President,

Hans Raabe whom I report to, and our Quality

Assurance Unit (Amanda Ulrey and Teri Beth

Wallace).

While I very much enjoy the type of work I

am currently doing, this transition seemed to get

me even further away from the pigmentation

field. But I found my ways back to it… There

was still a wild card in my sleeve when it came to

keeping my “color interest” alive: during my

transfer from Avon to IIVS I got to share the

work on this newsletter that you are now reading

with Dr. Prashiela Manga, as we took over from

the previous editor, Dr. William (Bill) Oetting.

And that’s how you all got to interact with me in

one way or another and how, unaware and

unknowingly, helped me stay in touch with the

field. Many of you know the story of my journey

as the editor of the newsletter so I will not

elaborate on that part here. I will just say that it is

a very rewarding experience and that I am

thankful to all of you as members of PASPCR

and newsletters contributors. Working with

Prashiela over the last almost six years grew into

a nice friendship and in a flawless collaboration

with the same goal: keeping the membership

informed through the means of the newsletters.

Still, while the PASPCR Newsletters are my

main venue of keeping in touch with the

pigmentation community at large, I have to admit

that I continued my work at IIVS with R&D (14,

15) and commercial studies focusing on melanin

modulation. Furthermore, I benefit from yet

another fruitful collaboration and friendship with

Dr. Stanca Birlea (University of Colorado,

Denver, CO, USA) which started way back, in

2002 in Netherlands while attending the 18th

International Pigment Cell Conference (IPCC)

held in Egmond aan Zee. We published several

pigmentation manuscripts together since then and

she was the one who actually introduced me to

the clinical aspect of the field through studying

vitiligo and the mechanisms behind this skin

condition (16, 17). This is yet another very

rewarding relationship that keeps me close to the

news in pigmentation and that grew during all

these transitions I have shared with you in my

column.

My journey continues and I would like to stay

close to the pigmentation community like to my

first “scientific love”; although I feel often times

as a satellite by not being 100% emerged in the

field anymore, I found it fascinating and the

scientists are very friendly and sharing. Please

continue being as such as this makes our colorful

scientific community unique. Thank you!

References:

1. Petrescu, S. M., Petrescu, A. J., Titu, H. N., Dewk, R.

A., Platt, F. M. (1997). Inhibition of N-glycan

processing in B16 melanoma cells results in

inactivation of tyrosinase but does not prevent its

transport to melanosome. J. Biol. Chem. 272, 15796-

05803.

2. Costin, G. E., Trif, M., Nichita, N., Dwek, R. A.,

Petrescu, S. M. (2002). pH-sensitive liposomes are

efficient carrier for endoplasmic reticulum-targeted

drugs in mouse melanoma cells. Biochem. Biophys.

Res. Commun. 293, 918-923.

3. pH-sensitive liposomes for targeted drug delivery. WO

2003032946 A2. Available at:

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http://www.google.com/patents/WO2003032946A2?cl

=en.

4. Pollock, S., Antrobus, R., Newton, L., Kampa, B.,

Rossa, J., Latham, S., Nichita, N. B., Dwek, R. A.,

Zitzmann, N. (2010). Uptake and trafficking of

liposomes to the endoplasmic reticulum. FASEB J. 24,

1866-1878.

5. Liposome treatment of viral infections. WO

2008088581. Available at:

http://www.google.com/patents/WO2008088581A3?cl

=en.

6. Costin, G.-E., Valencia, J. C., Vieira, W. D.,

Lamoreux, L. M., Hearing, V. J. (2003). Tyrosinase

processing and intracellular trafficking is disrupted in

mouse primary melanocytes carrying the underwhite

(uw) mutation. A model for oculocutaneous albinism

(OCA) type 4. J. Cell. Sci. 116, 3203-3212.

7. Costin, G.-E., Vieira, W. D., Valencia, J. C., Rouzaud,

F., Lamoreux, M. L., Hearing, V. J. (2004).

Immortalization of mouse melanocytes carrying

mutations in various pigmentation genes. Anal.

Biochem. 335, 171-174.

8. Costin, G.-E., Valencia, J. C., Wakamatsu, K., Ito, S.,

Solano, F., Milac, A. L., Vieria, W. D., Yamaguchi,

Y., Rouzaud, F., Petrescu, A. J., Lamoreux, M. L.,

Hearing, V. J. (2005). Mutations in dopachrome

tautomeras (Dct) affect eumelanin/pheomelanin

synthesis, but do not affect intracellular trafficking of

the mutant protein. Biochem. J. 391, 249-259.

9. Costin, G.-E., Hearing, V. J. (2007). Human skin

pigmentation: melanocytes modulate skin color in

response to stress. FASEB J. 21, 976-994.

10. FASEB J. Most-Read Articles during June 2012 thru

May 2013 – updated monthly. (2013). Available at:

http://www.fasebj.org/reports/most-read. Accessed on

4 June 2013.

11. Costin, G.-E., Raabe, H., Curren, R. (2009). The in

vitro safety testing strategy for skin irritation using the

3D reconstructed human epidermis. Rom. J. Biochem.

46, 165-186.

12. Costin, G.-E., Raabe, H. A., Priston, R., Evans, E.,

Curren, R. D. (2011). Vaginal irritation models: the

current status of available alternative and in vitro tests.

Altern. Lab. Anim. 39, 317-337.

13. Costin, G.-E., Birlea, S. A., Norris, D. A. (2012).

Trends in wound repair: cellular and molecular basis of

regenerative therapy using electromagnetic fields.

Curr. Mol. Med. 12, 14-26.

14. Costin, G.-E., Raabe, H. (2013). Optimized in vitro

pigmentation screening assay using a reconstructed

three dimensional human skin model. Rom. J.

Biochem. 50, 15-27 (in press).

15. Costin, G.-E., Raabe, H. (2013). Technical challenges

associated with dosing devices used for topical

treatment of three dimensional reconstructed

pigmented tissues. Rom. J. Biochem. (in press).

16. Birlea, S. A., Costin, G.-E., Norris, D. A. (2008).

Cellular and molecular mechanisms involved in the

action of vitamin D analogs targeting vitiligo

depigmentation. Curr. Drug Targets 9, 345-359.

17. Birlea, S. A., Costin, G.-E., Norris, D. A. (2009). New

insights on therapy with vitamin D analogs targeting

the intracellular pathways that control repigmentation

in human vitiligo. Med. Res. Rev. 29, 514-546.

Contact:

Gertrude-Emilia Costin, Ph.D., M.B.A. Study Director

Editor - PanAmerican Society for Pigment

Cell Research (PASPCR) Newsletters

Institute for In Vitro Sciences, Inc.

30 W Watkins Mill Road #100

Gaithersburg, MD 20878, USA

Phone: 301-947-6524

Fax: 301-947-6538

E-mail: ecostin@iivs.org

- // -

CLINICAL INSIGHTS

by Dr. Reza Nejati

Sensing the environment by skin

I am honored that Drs. Slominski and Costin

asked me to write the Clinical Insight column for

this number of the PASPCR Newsletter. As a

new member of the pigment cell research family,

I was unsure if I would have so much to say

compared to many experts in this field.

Nevertheless, I would like to share my

experiences in both clinical and research fields

which hopefully may inspire some young

researchers.

It seems like yesterday that I was an

energetic, curious boy growing up in a small city

in Iran. At age of 4 I saw a TV series on Louis

Pasteur’s life. His character, determination, and

perseverance impressed me profoundly, as did his

intellectual curiosity and desire for innovation.

Mistakenly assuming that he was a physician, I

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decided to follow in his footsteps by becoming a

doctor. It was my first dream of practicing

medicine, and research was an inseparable part of

it. While in medical school, pathology interested

me as it was the field that most closely resembled

my childhood notions about medicine.

Thoroughly hooked, I started my first pathology

residency upon graduation.

My first job after finishing residency was as

both a pathologist and Director of the Clinical

and Anatomical Laboratory of a state-run general

hospital. In addition to my hospital duties, I

established and ran a private clinical and

anatomical laboratory which was challenging

because I had to act as both a leader and a

technician. The lab worked at full capacity and

was expanding quickly. Everything looked

perfect until one night I asked myself a question:

“What had I done so far in my life?” I realized

that despite my enjoyment of clinical practice,

something seemed to be missing. It was the

scientific part of medicine which was my original

motivation for becoming a doctor. I remembered

Pasteur’s advice to young scientists at the

celebration of his 70th

birthday at Sorbonne:

[“Say to yourselves, first, “What have I done for

my instruction?” And as you gradually advance,

“What am I accomplishing?” Until the time

comes when you may have the immense

happiness of thinking that you have contributed

in some way to the welfare and progress of

mankind.”]

Thinking about a new pathology field where

advanced technologies, procedures and research

opportunities existed led me to come to the

United States and fulfilled my lifelong dream to

contribute to the scientific community. First, I

had the opportunity to work with Dr. Andre

Balla, Professor and Director of the Trans-

disciplinary Pathology Department at University

of Illinois at Chicago. I then went to Yale

University and had the great honor to work on

GYN and breast pathology services under the

leadership of Dr. Tavassoli. I worked at Yale

University till I joined the pathology residency

program at the University of Tennessee (UT).

Starting the second residency in pathology was

somehow different from the first one. It seems

like I have been given a second chance to

experience and see the whole story of my

professional life from the beginning to the end

and that I have the choice to do it in a different

way.

And so I started my residency. As time flies, I

first do my best to appreciate this chance and

enjoy every moment of my residency as well as

my time with my family. Secondly, bioscience

and molecular pathology are being merged in the

new pathology era, therefore we are in need of

more experts who have experience in both

clinical and bioscience fields. This expertise will

strengthen the bridge connecting research to

practice for the benefit of patients. Keeping these

two ideas in mind, I decided to choose a research

area during residency and start a basic research

project. At UT, I had the opportunity to attend

Dr. Slominski’s lectures and get firsthand

experience in his novel pigment cell research

projects. In particular, I was interested in his

lecture on the Regulation of cutaneous

hypothalamic-pituitary-adrenal (HPA) axis

homolog by ultraviolet light. To follow this

interest, I have juggled the busy residency life to

include work in Dr. Slominski’s lab on most

weekends.

The work on the HPA axis that I’ve been

doing has been fascinating. Historically,

proopiomelanocortin (POMC)-derived peptides

like α-MSH, ACTH and β-endorphin (β-END)

were the first stress-related mediators detected in

mammalian skin (Slominski et al., 1993). The

concept of the cutaneous establishment of a

peripheral hypothalamic-pituitary-adrenal (HPA)

axis equivalent defining as a cutaneous

equivalent of the HPA axis, became intuitive by

the discovery of corticotropin releasing hormone

(CRH) in skin and several other stress-related

factors, like Urocortin (UCN) (Slominski and

Mihm, 1996). These days, it is well documented

that mammalian skin expresses all functional

elements of HPA axis which influence local

homeostasis (reviewed in Slominski et al., 2007;

Skobowiat et al., 2011; Slominski et al., 2012).

The cutaneous HPA axis is not random but highly

organized and follows the central HPA axis

pattern, where CRH or UCN produced by skin

PASPCR

August 2013

23

cells and/or released by nerve endings interact

with CRH receptor type 1 (CRH-R1) to produce

POMC-derived β-END and ACTH, where the

latter stimulates the local production of cortisol

(COR) or corticosterone (CORT) (Ito et al., 2005;

Slominski et al., 2000; Slominski et al., 2005a;

Slominski et al., 2005b; Cirillo and Prime, 2011;

Hannen et al., 2011; Vukelic et al., 2011).

Cutaneous CRH, β-END, ACTH and

glucocorticoids (GCs) can regulate not only the

local (cutaneous) homeostasis, but also may

potentially affect central body homeostasis

influencing welfare, mood and food intake,

through the neural and vascular connections

(Slominski and Wortsman, 2000; Slominski et

al., 2000b; Slominski et al., 2012).

Since UVB is the major cutaneous stressor

and triggers the pigmentary and neuroendocrine

activities (Slominski et al., 2000; Slominski et al.,

2004; Slominski et al., 2012), we are currently

investigating its effects in mice (Skobowiat et al.,

submitted for publication). The preliminary data

of this study suggest that UVB may influence

elements of the HPA axis differently depending

on the genetic background and the animal

model(s). As our work continues, the animal

model(s) raise many other questions. Are the

genetic predetermined differences implicated in

the progression of skin tumors or pigmentary

disorders? Could any of the genetic differences

potentially be a predictor of therapy response?

Could elements of the cutaneous HPA axis be

used as targets for therapy or immunoresponse?

Can we use any of these as markers of survival

and metastasis? We hope that our future studies

open a new window to the mysterious world of

pigment cell disorders.

References:

Slominski A, Paus R, Wortsman J. On the potential role of

proopiomelanocortin in skin physiology and pathology.

Mol. Cell. Endocrinol 1993;93:C1-6.

Slominski A, Mihm M. Potential mechanism of skin

response to stress. Int. J. Dermatol 1996;35:849-851.

Slominski, A., Wortsman, J., Tuckey, R.C. and Paus, R.

Differential expression of HPA axis homolog in the

skin. Mol Cell Endocrinol 2007;265-266:143-149.

Skobowiat C, Dowdy JC, Sayre RM, Tuckey RC,

Slominski A. Cutaneous hypothalamic-pituitary-

adrenal axis homolog: regulation by ultraviolet

radiation. Am J Physiol Endocrinol Metab.

2011;301(3):E484-93.

Slominski, A.T., Zmijewski, M.A., Skobowiat, C., Zbytek,

B., Slominski, R.M. and Steketee, J.D. Sensing the

environment: regulation of local and global

homeostasis by the skin's neuroendocrine system. Adv

Anat Embryol Cell Biol 2012;212:1-115.

Ito, N., Ito, T., Kromminga, A., Bettermann, A., Takigawa,

M., Kees, F., Straub, R.H. and Paus, R. Human hair

follicles display a functional equivalent of the

hypothalamic-pituitary-adrenal axis and synthesize

cortisol. FASEB J 2005;19:1332-4.

Slominski, A., Zbytek, B., Semak, I., Sweatman, T. and

Wortsman, J., CRH stimulates POMC activity and

corticosterone production in dermal fibroblasts. J

Neuroimmunol 2005a;162:97-102.

Slominski, A., Zbytek, B., Szczesniewski, A., Semak, I.,

Kaminski, J., Sweatman, T. and Wortsman, J. CRH

stimulation of corticosteroids production in

melanocytes is mediated by ACTH. Am J Physiol

Endocrinol Metab 2005b;288:E701-6.

Cirillo, N. and Prime, S.S. Keratinocytes synthesize and

activate cortisol. J Cell Biochem 2011;112:1499-505.

Hannen, R.F., Michael, A.E., Jaulim, A., Bhogal, R.,

Burrin, J.M. and Philpott, M.P. Steroid synthesis by

primary human keratinocytes; implications for skin

disease. Biochem Biophys Res Commun 2011;404:62-

7.

Vukelic, S., Stojadinovic, O., Pastar, I., Rabach, M.,

Krzyzanowska, A., Lebrun, E., Davis, S.C., Resnik, S.,

Brem, H. and Tomic-Canic, M., Cortisol synthesis in

epidermis is induced by IL-1 and tissue injury. J Biol

Chem 2011;286:10265-75.

Slominski, A. and Wortsman, J. Neuroendocrinology of the

skin. Endocr Rev 2000;21:457-87.

Slominski, A., Wortsman, J., Luger, T., Paus, R. and

Solomon, S. Corticotropin releasing hormone and

proopiomelanocortin involvement in the cutaneous

response to stress. Physiol Rev 2000;80:979-1020.

Slominski, A., Tobin, D.J., Shibahara, S. and Wortsman, J.,

2004. Melanin pigmentation in mammalian skin and its

hormonal regulation. Physiol Rev 2004;84:1155-1228.

Contact:

Reza Nejati, M.D.

University of Tennessee Health Science Center

Department of Pathology & Laboratory Medicine

930 Madison 5th

floor

Memphis, TN 38103, USA

E-mail: mnejati@uthsc.edu

PASPCR

August 2013

24

MEMBERS IN THE NEWS

Yale News (Yale University) recently featured one

of the recent studies performed in collaboration by

Yale University, University of Colorado and

Denver Police Department Crime lab and authored

by several PASPCR members. The study was

published in PLOS one and is entitled “A

melanoma brain metastasis with a donor-patient

hybrid genome following bone marrow

transplantation: first evidence for fusion in human

cancer” by R. Lazova, G. S. Laberge, E. Duvall, N.

Spoelstra, V. Klump, M. Sznol, D. Cooper, R. A.

Spritz, J. T. Chang and J. M. Pawelek.

Visit http://news.yale.edu/2013/06/26/how-

cancer-spreads-metastatic-tumor-hybrid-cancer-

cell-and-white-blood-cell to read the press release

by Yale University and to get direct access to the

original paper.

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POSITIONS WANTED/AVAILABLE

Postings for Positions Wanted will be open only

to members of the PanAmerican Society for

Pigment Cell Research (PASPCR) or its sister

Societies (ASPCR, JSPCR and ESPCR). Postings

for Positions Available will be open to all

individuals and institutions so long as the position

is related to pigment cell research. Please send

postings to paspcr.newsletters@gmail.com.

The postings will remain on the Positions

Wanted and Available section of the PASPCR

Newsletter and on the web page for 1 year, unless

other arrangements are made. Please provide an

expiration date for any submitted posting if less

than 1 year. Final decisions will be made by the

Publications Committee of the PASPCR.

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