Science in the Pursuit of Health®

www.wadsworth.org

The Wadsworth Center laboratories stand at the forefront of biomedical and environmentalsciences and their interplay.

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Innovative, multidisciplinary research. Complex diagnostics and novel

detection methods. High-tech instrumentation and state-of-the-art laboratory

services. All are components of the dynamic scientific community that is

the Wadsworth Center of the New York State Department of Health.

Building on more than a century of excellence as the state’s public health

laboratory, the Center continues as a premier biomedical institute that

merges clinical and environmental testing with fundamental, applied

and translational research.

Today, Wadsworth Center scientists use both classical and contemporary

approaches to study environmental and biological questions related to

human health and disease. They develop advanced methods to identify

microbial or chemical threats; study drug resistance, emerging infections,

and environmental exposures; manage the country’s most comprehensive

diagnostic and environmental testing laboratory permit program; oversee

extramural research programs on stem cells, breast cancer and spinal cord

injury; and train the next generation of scientists through undergraduate,

graduate, postdoctoral and visiting scientist programs. Their efforts

embody Science in the Pursuit of Health.®

The Center serves a vital role in the New YorkState Department of Health’s efforts to protectand promote the health of New York’s citizens.

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Landmarks and Achievements

1900 1910 1920 1930 1940 1950

1914The Antitoxin Laboratorydesignated the Division ofLaboratories and Research;Augustus B. Wadsworthnamed director

1926First Standard Methods ofanalysis for public healthtesting published

1941Syphilis test standardizedwith the chemically definedantigen, cardiolipin (Dr. MaryPangborn)

1950Nystatin discovered: the first safe and effectiveantifungal antibiotic (Drs. Elizabeth Hazen and Rachel Brown)

1901State Antitoxin Laboratoryestablished to standardizeand manufacture antitoxin for diseases such asdiphtheria

1948Coxsackie virus isolatedand characterized

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1960 1970 1980 1990 2000 2010

1965A model newborn screening programestablished and new assays developed,allowing detection of more treatable conditions

1965The country’s first stateclinical laboratory permitprogram launched

1978-80Sophisticated methods developed to assess toxicity of complex environmentalmixtures

1978Studies on arbovirusesbegin and over timeexpand to include easternequine encephalitis,dengue, West Nile,chikungunya and Zikaviruses

2001Sensitive biomonitoringanalytics used to detectlow levels of environmentaltoxins in human samples

2006Whole genome studiesdefined genes associatedwith Parkinson’s disease,allowing genetic testing for disease susceptibility

2006HIV tropism assaydeveloped to predictdisease progression

2012Applied Genomic TechnologiesCore breaks record for basessequenced on Ion Torrent™PGM™ Sequencer with 316chip: 785 million bases ofSalmonella DNA sequenced in a single run

1991Brain-computer interfacesystem developed; goal isto restore communicationand control to peopleseverely paralyzed by ALS,strokes or otherdevastatingneuromuscular disorders

1984Mobile genetic elementsknown as intronsdiscovered in bacteria

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Group II Intron Structure

1981Electron microscopy andcomputer processing used to analyze the 3Dstructure of largebiomolecules, eventuallybecoming a new standardin structural biology

1983Vaccinia virus used as avector to express selectedgenes from pathogens tomake safer vaccines

2013New prototype brainmapping techniquelicensed. Improves safetyand reduces duration ofneurosurgical procedures

2013First state in the country to screen newborns foradrenoleuko dystrophy (ALD)

2015The National Center forAdaptive Neuro technologiesopened. Research conductedto improve diagnosis andtreatment of stroke, spinalcord injury, traumatic braininjury, and other devastatingneurological conditions

2015First state public healthlaboratory to use wholegenome sequencing foroutbreak investigation, applied to Legionellaoutbreak

2016First state public healthlaboratory to perform wholegenome sequencing onclinical TB samples

2008First demonstration thatbrain activity recordedfrom the scalp can control a computer cursor

2017Dr. Joachim Frank awardedNobel Prize in Chemistry for pioneering work in cryo-electron microscopy

Public Health GenomicsCompletion of the Human Genome Project in 2003 made headlines, created greatexpectations and laid the groundwork for precision medicine. It also spurred tremendoustechnological advances, such as next-generation sequencing. Individuals already benefitfrom the identification of mutations that cause disease as well as genes and genevariants that impact drug metabolism and effectiveness of treatment. Yet, the translation of genetic discoveries into widespread clinical applications has just begun.

Population health, a domain of public health, has also benefitted. At WadsworthCenter, new genomic technologies play a major role in both clinical and researchprograms, in disciplines ranging from infectious diseases to genetic disorders.

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SEQUENCING APPLIED

• The Biodefense Laboratory is continually improving methods

to detect and characterize biothreats, and today uses sequencing

in the surveillance of select agents, such as Clostridium botulinum,

which causes botulism.

• Foodborne disease outbreaks, which sicken one in six Americans each

year, are tracked more precisely and rapidly with DNA sequencing.

Since 2012, in collaboration with the Food and Drug Administration,

the Wadsworth Center has fully sequenced many genomes of

the bacterium Salmonella, a frequent cause of food-borne illness.

• Newly emerging pathogens are more readily identified, and known

infectious agents, such as E. coli, influenza, West Nile virus and

M. tuberculosis, are being more closely studied.

• The pioneering Newborn Screening Program is employing DNA

sequencing technologies to determine the genetic basis of diseases

detected in infants, and to identify novel genetic causes of birth defects.

Next-generation sequencing technologies continue to accelerate this

progress, and are now routinely employed in our testing laboratories.

Wadsworth Center’s extensive experience with sequencing, along with

robust computing capabilities and bioinformatics expertise applied

to analysis of genomic data, has led to partnerships with federal

and state agencies, and academic and research centers. Advanced

molecular technologies promise to transform clinical diagnostics,

patient care and the tracking of public health threats, including

hospital-acquired infections and drug-resistant pathogens.

At Wadsworth Center, genomic technologies have played a major role in both diagnostic and research programs.

New York’s smallest citizens get off to a healthy start thanks to a comprehensive program that screens all infants for detectable,treatable conditions. An acknowledged leader in newborn screening,Wadsworth Center capitalizes on technological and medical advances, making newborn screening the Center’s largest program.

• Around 245,000 infants screened and over 11 million results reported annually

• 47 conditions screened using 5 methodologies

• 63 staff operating 10 hours each weekday

• Over 2,500 screen positives referred each year

• 70 specialty treatment centers to which infants are referred

• Average of 350 case updates per month

• Over 2,200 phone calls monthly related to referrals and follow-ups with physicians or the public

• Approximately 150 questions e-mailed to the program monthly

Newborns’ blood specimens collected from aheel prick onto filter paper forms are “punched”to remove samples for processing

Newborn Screening: By the Numbers

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MOLECULAR GENETICS

Control of gene expression is critical to the normal functioning of an

organism. Novel computational approaches devised by Wadsworth Center

scientists are uncovering DNA and RNA sequences that regulate gene

expression in diverse organisms, dictating when, where and how much

protein to manufacture. Molecular geneticists build on this regulatory

information as they investigate cellular processes that cause genomes

to alter or adhere to genetic instructions. Knowledge about genome

evolution and conservation informs studies of normal development,

inherited disorders and cancer. Similarly, an understanding of non-coding

DNA reveals how these sequences create diversity within and among

species, while retaining a blueprint for development and function.

Cellular and MolecularStructure Analysis

While the majority of attention in recent years has focused on genes and genomes,ultimately it is a cell’s macromolecules (proteins and RNA) that do the actual work,including everything from regulating cell growth and division, to maintaining cellularenergy supplies and cell structure. Most of these macromolecules function only as part of larger and more complicated structures, such as membranes, filaments and ribosomes, the complex molecular machines that fabricate proteins.

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TODAY’S RESEARCH, TOMORROW’S SOLUTIONS

Using cutting-edge structural and biological techniques to study these

fundamental cellular processes in normal and diseased conditions, Wadsworth

Center researchers elucidate molecular details of interactions between cellular

components involved in cell division, locomotion, muscle contraction, mechanical

sensing, gene expression and cancer.

The goals are to not only understand how disease develops in humans, but also

to identify novel drug targets and mechanisms of drug resistance in pathogens.

3D cryo-EM structure of the small (28S) ribosomal subunit present within the mammalian mitochondria. Yellow: 12S rRNA; Purple: r-proteins.

Image isn’t everything, but for some scientists, visualizing their pathogen, protein or process of interest can yield new insights. At Wadsworth Center, cell biologists, structural biologists and other life scientists producedata that are visually arresting as well as scientifically meaningful. Using sophisticated instrumentation, theygenerate representations of cells and biomolecules to better understand their function — pathogens invadinghost cells, cells caught in the act of dividing, organelles mapped in three dimensions, or proteins and nucleicacids bound in macromolecular complexes. These colorful, information-rich images have won internationalawards, been featured on note cards, and graced the covers of textbooks and prestigious journals, includingScience, Cell and the Proceedings of the National Academy of Sciences.

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Life Science as Art

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1 Cell signaling enzyme dynamics predicted by simulation

2 Structure of super antigen-immunoreceptors ternary complex

3 Confocal image of neurons in cerebral cortex

4 Relocation of chaperone proteins in herpes virus-infected cells

5 Vertebrate somatic cell initiates cell division(prophase)

6 Mammalian mitochondrial ribosome by 3D cryo-electron microscopy

7 X-ray structure of hepatitis C virus RNA polymerase substrate complex

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Neuroscience andNeurotechnology

Recent advances have transformed neuroscience research. Wadsworth Center scientistsand engineers are augmenting and exploiting these advances in many different areas.Using sophisticated tools and animal models, researchers study the genetic, anatomical,physiological, and immunological bases of neurodevelopmental, neurodegenerative,environmental, and traumatic disorders such as autism and epilepsy.

The recent realization that activity-dependent plasticity occurs across

the entire central nervous system (CNS) throughout life, and that

new technology can support complex, real-time adaptive interactions

with the CNS to induce and guide this plasticity, represents a major

breakthrough. This plasticity enables investigators to develop powerful

new research tools and therapeutic methods that can restore useful

function to people disabled by injury or disease. Yet another approach

employs sophisticated software to translate the brain’s electrical activity

into control of a computer cursor or robotic arm. Strong emphasis is

placed on translating basic scientific advances achieved in the laboratory

into clinical studies in humans and eventually into clinical practice.

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You Think. You Can.By simply thinking, severely disabled users of a brain-computer inter face (BCI) pioneered at Wadsworth Centercan compose and send e-mails, converse using a voice output utility, and control their environment, by turning on a light for example. The award-winning BCI system translates electrical signals detected from the scalp into users’commands, giving keyboard-like control of computer-based functions.

The non-invasive system consists of an electrode cap that detects electroencephalographic (EEG) activity from the scalp, an amplifier that records key brain waves, a computer and sophisticated software. The researchproject has moved from laboratory to living room, with the development of a portable, affordable system usefulfor everyday tasks for the target population, the most severely disabled. The first home-based user, a workingneuroscientist with ALS (Lou Gehrig’s disease), used BCI to communicate by e-mail with his research team.

Public health and basic research programs converge on infectious agents, with Wadsworth Center scientists seeking to improve detection of disease-causing organisms and understand their fundamental properties. Staff develop and validate tests to identify pathogens in order to monitor and manage diseaseoutbreaks. While not abandoning traditional methods, they embrace modern molecular technologies thatrapidly determine the source of disease transmission.

At the same time, researchers dissect the lifestyles of bacteria, viruses, parasites and fungi to understand how these infect and interact with their human host. For example, detailed knowledge about key proteins and the cellular machinery that pathogens require for virulence can aid in the development of novel drugs or vaccines that interrupt the disease process.

Infectious Diseaseand Host Defense

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VIROLOGY

Wadsworth Center scientists probe the mechanisms that viruses

use to hijack a human host’s replication machinery, causing diseases

from AIDS to Zika. They examine viral proteins that help assemble

genetic material into infectious particles and analyze how changes in

these proteins allow the SARS coronavirus and other pathogens to

adapt to new hosts. Arbovirus researchers concentrate on the ecology

and evolution of mosquito-borne viruses, such as West Nile, Zika,

chikungunya and their insect vectors, while clinical virologists test

for the presence of these viruses in patients.

The clinical program also conducts outbreak investigations, performs

surveillance, develops tests for emerging pathogens and collaborates

with the World Health Organization and the Centers for Disease

Control and Prevention (CDC) to detect the earliest appearance of

new strains of influenza. Other Wadsworth Center laboratories chart

the prevalence in and spread of viruses to other hosts, including

rabies in bats and other animals.

ZOONOTIC AND VECTOR-BORNE DISEASES

Zoonotic diseases constitute the majority of emerging diseases due

to climate and environmental changes and the rise in international

travel and commerce. Surveillance studies show clear evidence

of the spread of tick-borne diseases northward, and similar trends

are observed for diseases transmitted by mosquitoes. Zoonotic and

vector-borne diseases are therefore priority focus areas.

Highly unique facilities and resources, such as the Griffin insectary,

are available to researchers who possess a broad range of expertise

in ecology, cell biology, molecular biology, molecular genetics,

structural biology, biochemistry and immunology.

Pathogens of interest include Zika, West Nile, chikungunya, dengue,

eastern equine encephalitis, rabies and Powassan viruses, as well

as other zoonotic agents such as Borrelia (causing Lyme disease).

Zoonotic diseases transmitted directly to people from vertebratehosts such as bats, or by mosquitoes, ticks and other vectors, account for many emerging diseases.

Above: Ixodes scapularis, a tick capable of transmitting the causative agent of Lyme disease and other organisms. Below: Aedes aegypti mosquito during a blood feeding.

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ANTICIPATING THE NEXT EPIDEMIC

Wadsworth Center arbovirologists study the biological factors (the

genetics of the vector, virulence of the pathogen, susceptibility of

the host) in combination with the non-biological factors (temperature,

precipitation, land development) that impact transmission intensity

and perpetuation of pathogens.

Long before Zika was a household name, research at Wadsworth Centerled to the expectation that Zika would become “the next epidemic.”

As a result, tests with enhanced specificity were developed and this

laboratory became one of the first laboratories besides CDC capable

of rapidly responding to Zika outbreaks.

As clinical samples flooded the laboratory, one of Wadsworth Center’s

immunologists identified an area for improvement in an existing Zika

serology test and after intensive research and testing, was co-inventor

of a new and highly specific test for Zika virus infection.

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IMMUNOLOGY

The immune system sometimes misses the mark, either failing to

mount a response against foreign elements or mistakenly targeting

host cells, leading to autoimmune diseases. Wadsworth Center

investigators parse the immune system, studying its component cells

and the mechanisms involved in host defense against bacterial and

viral infections. Researchers consider factors that modulate immuneresponse, including diet, environmental pollutants, aging, stress,

hormones and genetic makeup. Avenues for novel therapeutics are

assessed, such as the properties of mucosal antibodies that inhibit

infection and the structure of immune molecules that mediate

a protective response. Scientists develop tests to measure specific

serum antibody levels for emerging and newly epidemic diseases,

among them Powassan encephalitis, Lyme and Zika.

PARASITOLOGY AND MYCOLOGY

Fungal and parasitic infections that debilitate the very young, the

aged and immunocompromised patients, especially those with AIDS,

highlight the need for more effective treatments.

Wadsworth Center researchers study yeasts, molds and other medically

important fungi using recombinant DNA technology and animal models

to understand how the pathogens cause disease. Their ultimate goal

is to identify genes or proteins useful for diagnosis or development

of novel drugs.

Similarly, scientists investigate parasites, with a particular focus on

the causative agents of malaria, toxoplasmosis and cryptosporidiosis,

the latter a potentially life-threatening gastrointestinal illness.

Traditional and molecular diagnoses of molds, yeasts and parasites

from clinical specimens and the environment are performed, as well

as more complex confirmatory testing.

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BACTERIOLOGY

The study of bacterial pathogens incorporates conventional and

molecular diagnostics, surveillance, strain typing and research.

Investigators focus on Mycobacterium tuberculosis to understand how

the bacterium that causes tuberculosis lies dormant within the lungs,

then overcomes the host’s immune defenses to initiate disease.

Wadsworth Center scientists develop and validate molecular tools

to detect and identify bacteria in complex clinical and environmental

samples, methods that have helped address disease outbreaks

caused by E. coli O157:H7 and Legionella pneumophila.

Naturally occurring outbreaks are tracked with DNA typing (bacterial

fingerprinting) to confirm links between organisms causing human

disease and their presence in implicated food or other products. This

information is incorporated into a national database to proactively

identify outbreaks that may affect neighboring states. This expertise

also aids in the assessment of biothreat samples for infectious agents

that may have been deliberately disseminated.

PUTTING THE BRAKES ON OUTBREAKS

Culture (growth in vitro) is the classical approach to Legionella testing

of environmental samples, but Legionella bacteria are slow-growing

and the submitted samples are usually heavily contaminated with

other bacteria. Obtaining results by culture can take a long time,

delaying the required public health response.

Instead, the Bacteriology Laboratory first screens water samples using

a rapid, in-house developed, multiplex real-time PCR assay. Positive

samples are then cultured, and isolates are genotyped by pulsed-field

gel electrophoresis (PFGE).

For outbreak analysis, the Applied Genomic Technologies Core

performs whole genome sequencing of human and water isolates

and the Bioinformatics Core performs sequence analysis of the

data, which confirms and enhances the PFGE results.

This work contributed to the identification of a contaminated cooling

tower in NYC responsible for significant morbidity and mortality during

one Legionella outbreak.

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19

ANTIMICROBIAL RESISTANCE

With the introduction of antibiotics approximately 70 years ago, minor

wounds and illnesses ceased to be life-threatening. In the intervening

years, with the widespread use of these medications, many organisms

have become resistant. In 2016 in the United States alone, over two

million people became ill and over 23,000 died because of antibiotic

resistant organisms. For some organisms, even antibiotics normally

reserved as the last line of defense no longer work, and no effective

antibiotics exist to treat the patient.

In 2016, Wadsworth Center became one of only seven laboratories

in the United States designated by CDC as an Antibiotic Resistance

Regional Laboratory, testing specimens from an eight-state region

for seven threats deemed as urgent or serious in the CDC Antibiotic

Resistance threat report. In addition, the Mycology Laboratory is

designated as one of only four in the country to test certain fungal

pathogens for antifungal resistance.

In close collaboration with the CDC, Wadsworth Center scientists

work on special projects designed to address specific antimicrobial

resistance threats, using both gold standard and cutting-edge

technologies to provide for faster outbreak detection and response,

better tracking of antimicrobial resistance, and provision of real-time

actionable data to prevent and combat future threats in the Northeast.

COMBATING TUBERCULOSIS

Wadsworth Center is the first state public health laboratory in the

nation to perform whole-genome sequencing as a clinical diagnostic

test for tuberculosis (TB) and to use the results to predict the best

treatment for the patient.

This one test can replace nearly a dozen tests, reducing turnaround

time for diagnosis and susceptibility testing for first- and second-line

treatments from 41 to 11 days, for example. Even greater decreases

in turnaround time are anticipated with further improvements

in technology.

Since TB infection can continue to be spread for up to two to three

weeks after initiation of medication, quickly determining and prescribing

the correct treatment greatly reduces the risk for disease transmission

and spread throughout the community.

A Mycobacterium tuberculosis phylogenetic tree of strains isolated from new TB patients in New York informs epidemiologicalinvestigations and provides insight into drug resistance.

Rapid identification of biological and environmental threats is an everyday

event at New York State’s public health reference laboratory.

BIOLOGICAL

• Staff have identified more than 30 emerging and re-emerging disease-

causing organisms in recent years, including West Nile virus, Hantavirus,

Zika, Powassan virus, Legionella, Listeria and Cryptosporidium.

• In a single year, bacteriologists implemented almost two dozen new

molecular-based methods and tested more than 10,000 specimens

using such tests, in some cases linking New York State patients with

nationwide foodborne disease outbreaks.

• Virologists developed a molecular test to simultaneously detect 11

respiratory viruses in a single reaction, and used archived influenza

specimens to demonstrate the evolution of the influenza virus over

a single flu season.

• Rabies specialists developed and licensed a novel approach to producing

a biological reagent used by all public health laboratories as part of the

gold-standard rabies diagnostic test.

• The Biodefense Laboratory analyzed more than 1,000 suspicious

materials and clinical specimens for the presence of Bacillus anthracis

following the anthrax attacks in the fall of 2001, and continues

to assess potential biothreats to this day.

CHEMICAL AND RADIOLOGICAL

• The federal government designated Wadsworth Center as one of only

two sites to evaluate prototype mobile units for screening environmental

samples to rule out potential hazards, such as nerve agents, explosives

or radiation, prior to biological testing.

• As a Level 1 Laboratory in the Laboratory Response Network for Chemical

Threats, staff provides surge-capacity testing to the CDC, detecting many

toxic chemicals including mustard gas and nerve agents.

• As a member laboratory of the Food Emergency Response Network,

Wadsworth Center’s Environmental Health Program ensures the safety

of the nation’s food supply by testing for the presence of radiation.

• The Nuclear Chemistry Laboratory partners with the Bureau of

Environmental Radiation Protection to provide analytical support

during radiological events through measurements of milk, soil,

air and vegetation samples collected by trained DOH staff.

Training for preparedness takes place in the fieldand at the laboratory bench with first respondersand other critical partners.

Reference, Readiness and Response

Determining PFOA levels in serum

20

Scientific and technological advances of the last years allowed for the detection of more andmore minute quantities of contaminants in complex environmental samples. Complementingthat capacity today is the emerging ability to directly measure environmental chemicals or theirbyproducts in clinical specimens, called biomonitoring. At Wadsworth Center, scientists employthese and other approaches to monitor the environment for public health threats, assessindividual exposures, and investigate the relationships between environmental, occupational,and dietary exposures and health effects. Their studies also examine the underlying interactionsof environmental toxicants with immune, endocrine, neurologic and genetic systems.

EnvironmentalHealth Science

Biomonitoring measures personal environmental exposures, rather than

inferring exposure from chemical concentrations in air, water or soil.

This approach directly quantifies the suspect chemical, its metabolites

or reaction products in human specimens. Wadsworth Center scientists

are developing methods to measure biomarkers of exposure in serum

and urine in order to identify individuals at risk. Biomonitoring can help

determine the relationship between exposure and disease, and target

prevention and remediation efforts more appropriately. For example,

an objective measure of exposure to emissions from the World Trade

Center disaster in state employees and National Guardsmen will

support investigations of future health effects.

BIOMONITORING IN ACTION

• Measurement of nicotine metabolites to determine the effect of

smoking law changes on exposure of bar and restaurant workers

to secondhand smoke.

• Assessment of fish-borne exposure to bioaccumulative flame

retardant chemicals in anglers.

• Evaluation of mercury exposure in New York City adults to identify

at-risk populations and identify sources of exposure.

• Response to accidental or deliberate release of toxic chemicals

to identify agents, determine exposure and assess re-occupancy.

• Collaboration with the local community to identify exposure to enriched

and depleted uranium in former factory workers and local residents.

• Assessment of perfluorochemical exposures among populations

affected by drinking water contamination.

• Evaluation of early life exposure to perfluorinated compounds

(PFCs) via analysis of newborn screening bloodspots.

Biomonitoring

22

Use of bloodspots in detecting declining levels ofperfluorooctane sulfonate (PFOS) in New York Stateinfants from 1997 to 2007. Production of thesePFCs was phased out from 2000 to 2002.

23

ENVIRONMENTAL EXPOSURES AND CHILDREN

Wadsworth Center works with the National Institutes of Health and five

other centers to test children’s blood and urine for the presence of

organic chemical contaminants, such as flame retardants, insecticides,

and toxic heavy metals, including lead, cadmium, mercury and

arsenic. Results provide accurate measurements that support research

studies of the impact of environmental exposures on children’s

health. Wadsworth Center plays a key role in overseeing the quality

of measurements for toxic metals in blood and urine.

BISPHENOL A EXPOSURE

Wadsworth Center conducts pioneering human biomonitoring studies

on the occurrence of bisphenol A (BPA) in currency notes, paper

receipts, paper products and clothing, and the exposure of New Yorkers

to this compound. BPA, produced in quantities of over eight billion

pounds each year worldwide, is used in the production of polycarbonate

plastics, and in the resin lining of food and beverage cans. BPA is now

being found in foodstuffs and house dust, as well as in human urine and

breast milk. BPA is an endocrine-disrupting chemical. Human exposures

to BPA have been associated with a wide array of adverse health

outcomes, including obesity and diabetes. As concern grows regarding

the toxic effects of BPA, it is gradually being replaced in many consumer

products with compounds such as bisphenol S. Changes in regulations

for the use of bisphenols in some countries have changed the patterns

of bisphenols found in urine. The method developed in the laboratory

is being applied to a large-scale study of the exposure of newborn

babies in upstate New York to BPA for examining the association

of exposure to health outcomes.

24

TOXICOLOGY

Differences in how chemicals are metabolized can be explained,

in part, by an organism’s own genetic make-up. Variant forms of

enzymes that bioactivate foreign compounds, whether therapeutic

drugs or environmental pollutants, can predispose individuals

to toxic or beneficial effects.

Wadsworth Center scientists study variants of a complex metabolizing

system known as cytochrome P450. They investigate the influence

of metals, fluoride, nanoparticles and other foreign substances

on P450 function, and study the enzymes’ differential expression

in multiple tissues.

Other efforts to identify environmental triggers of disease examine

alterations in nervous system function produced by exposure to

contaminants such as PCBs, pesticides, methylmercury and engine

exhaust fumes.

The Trace Elements Laboratory conducts biomonitoring research

for lead, arsenic and mercury, and performs analyses in support

of public health lead poisoning programs.

A novel X-ray fluorescence instrument detects lead (Pb) andstrontium (Sr) concentrations in goat shin bone, while other tracemetal analyses take place in a clean-room environment.

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39% to 51%

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Percent of Homes with Basment Radon Levels Greater than 4 pCi/L

ENVIRONMENTAL CHEMISTRY

Accurate measurement of radioactivity and chemical contaminants

is essential for surveillance of drinking water supplies, nuclear power

plants and indoor air, or for response to public health emergencies.

Programs to characterize occurrence and exposure to natural radio -

activity largely focus on radon, with the development of township-level

maps indicating indoor radon-potential. Community water supplies

around nuclear power reactors are monitored for radioactivity, and

preparedness drills are conducted to improve response to potential

accidents or terrorism.

In addition to monitoring regulated chemicals in the environment,

Wadsworth Center scientists develop novel methods to detect

contaminants of concern, such as flame retardants, pesticides and

pharmaceuticals present in the environment and food. Studies aim

to evaluate the bioaccumulation, food-chain transfer, and human

exposures of emerging chemical toxicants, and to develop

biomarkers of human exposure.

ATMOSPHERIC SCIENCE

The earth’s atmosphere is a mixture of particles and gases from

natural and man-made sources, including airborne products of

combustion and manufacturing. Ultra-fine particles are a special

concern for their association with cardiac and pulmonary disease,

and climate change. Scientists identify the chemical constituents

of these fine particles and identify their sources. Secondary aerosols

formed from chemical reactions also affect air quality, producing

acid rain and altering ozone levels.

Researchers study reactions in cloud, ice and snow environments

to understand the production of stratospheric ozone; analyze clouds

for the occurrence and production of acidic sulfate, the cause of acid

rain; and characterize indoor pollutants to understand the relationship

between chemical exposure and asthma.

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Persistent organic pollutants found in everyday products from flame retardants (PBDE) to stain repellents (PFOA), and even those banned decades ago (PCB), are studied for potential health effects.

25

PCBPBDE PFOA

Micron-sized organisms whose presence in recreational watersindicates bacterial contamination take time to identify. The lagbetween sample collection and reporting means that day-old data, at best, inform decisions on beach closings. Wadsworth Center has addressed this vital issue by developing a molecular-based assay that is hours faster than culture, the gold standard. ThisEnvironmental Protection Agency-based test amplifies a segment of an Enterococcus gene, giving rapid and accurate results.

Enterococcus isn’t the only thing living in recreational waters. As part of public health responses, Wadsworth Center tests for Giardia,Cryptosporidium and other waterborne pathogens. Molecular methodsare also used to discriminate human, agricultural and avian sources of fecal pollution impacting beaches and to rapidly differentiate toxin-producing species of blue green algae from their non-toxiccounterparts, delivering the news bathers need to hear faster.

DRINKING WATER QUALITY

Wadsworth Center scientists develop state-of-the-art methods toquantify the sources, distribution, fate and transport of waterbornetoxicants, including persistent organic pollutants (e.g., PCBs anddioxins), perfluorinated compounds and heavy metals. These rapid and accurate analytical tools aid routine monitoring of water resources and improve response to public health emergencies.

Do (or Don’t) Jump in the Water

26

27

MEDICAL MARIJUANA AND CANNABINOID TESTING

Enhancing the safety of Medical Marijuana in New York, Wadsworth

Center scientists perform over 12,000 tests per year for contaminants

such as pathogenic microorganisms, heavy metals, mycotoxins and

pesticides. Equally as important, they confirm the cannabinoid potency

of each product type.

Testing of illicit synthetic cannabinoids for law enforcement agencies

is literally a moving target comprised of a large, ever-growing, and

continually evolving family of potent chemicals. Because no laboratory

knows prior to testing exactly what chemical they are looking for,

specialized extraction, separation, and analysis, called untargeted

analysis, must be performed.

28

Scientists at Wadsworth Center don’t work in isolation. They conferand collaborate, whether their laboratories are separated by hallwaysor miles. Extensive core facilities facilitate these cross-disciplinarycollaborations, providing investigators and their collaborators of all disciplines with expertise and access to specialized equipmentand services.

Working together, they bridge scientific divides, drawing upon theirdisparate expertise to wrestle with a particular challenge. For example,multiple lines of work focus on arthropod-borne agents such as West Nile virus (WNV) and Zika:

• Clinical laboratory groups test for these viruses in patients to aid decisions on treatment.

• Other groups concentrate on testing for these viruses inmosquitoes to study the transmission and pathogenesis, as wellas the ecology and evolution of the virus and its insect hosts.

• And molecular biological research is geared towardunderstanding the machinery that replicates the viral RNAgenome, with the goal of identifying molecular targets for antiviral therapy and screening prospective drugs.

It is this synergy of clinical science combined with basic and appliedresearch that uniquely describes New York’s public health laboratory.

Crossing Corridors, Crossing Disciplines

CDC Pu

blic H

ealth

Imag

e Library

West Nile virus

Saliva collection from West Nile-infected mosquito

Public Health Science from A to Z

29

A B C

ID EG H

Anthrax Antibiotic resistanceAsbestosAutism Autoimmune disorders

Hepatitis Hereditary disease HIVHistoplasma

MMalaria Medical marijuana Meningococcal diseaseMicrocystinMicrobiomeL Lead poisoning

ListeriosisLyme disease

Influenza

NNeural plasticityNewborn screeningNorovirus OOlfaction

OpioidsOrganic solventsOutbreaksOutdoor airOzone PParasites

Phthalates PFOA

R SSARS SarinSpinal cord injurySyphilis TTickborne disease

TrichinosisTuberculosisTaenia (tapeworm)

VVaccine developmentViral infections WZ Zika

Zoonotic diseases

Bacterial infections Birth defects Bloodborne virusesBiomonitoringBorrelia

ChikungunyaChemical pollutants Cystic fibrosisClostridium

Dengue virus Developmental disordersDrug toxicity

E. coli O157:H7EnterococcusEpilepsy

Giardiasis

FFlavivirusFrancisella

JJapanese Encephalitis virusJamestown Canyon virusJunin virus

K Klebsiella

QQ fever

UUranium, enriched and depletedUrine

West Nile virusWhooping coughWTC

X YYellow feverYersinia pestis

Rabies Radon

X-ray crystallographyXDR

Kawasaki virus

The analysis of human clinical specimens or samples collected from the environmentprovides information that is essential to health assessment and disease or exposureprevention. The quality assurance and regulatory oversight programs of New YorkState that reside in Wadsworth Center ensure that hospital-based and commercialtesting laboratories provide accurate, reliable and reproducible test results.

Ensuring Quality ofLaboratory Services

31

CLINICAL LABORATORIES AND BLOOD BANKS

Wadsworth Center’s Clinical Laboratory Reference System oversees

the permitting of laboratories testing human specimens collected

in New York. The reference system accredits clinical diagnostic

laboratories, validates and approves laboratory methods and materials,

provides consultation and reference testing, conducts cooperative

research relevant to methods and materials, inspects laboratories,

and regularly ensures compliance with proficiency testing regulations.

Increasingly, clinical laboratories are developing in-house diagnostics,

known as laboratory-developed tests (LDTs), which are not subject

to approval by the Food and Drug Administration. Wadsworth

Center’s reference system requires that their performance claims

be documented before the new tests may be used. The reference

system is a multifaceted program that is integrated throughout

Wadsworth Center, as well as with other New York State Department

of Health entities and governmental agencies.

ENVIRONMENTAL LABORATORIES

Any environmental laboratory testing samples collected in New York

must be certified by Wadsworth Center’s Environmental Laboratory

Approval Program (ELAP). Laboratories are certified for testing chemical

and bacteriological pollutants in a range of sample types, including

drinking water, natural waters, waste effluents, soils, sediments,

chemical waste and air. Certification is based on successful participation

in proficiency testing, on-site inspection of facilities and appropriate

staffing. Perhaps unique among state accreditation programs is ELAP

certification for detecting Biological Critical Agents in environmental

samples, such as the causative agents of anthrax, botulism and plague.

Summa® canisters collect ambient air and the samples areanalyzed for the presence of volatile organic compounds.

TISSUE BANKS

Developing and enforcing standards of practice for tissue banks and

transplantation facilities, the Tissue Resources Program ensures the

safe and ethical solicitation, collection, processing, distribution, and

use of human tissue in New York State. Banks that recover, process,

store and/or distribute nontransplant bodies and/or anatomic parts

for medical research and/or health professional education must also

be licensed and meet requirements for record keeping and tracking.

PHYSICIAN OFFICE LABORATORIES

In New York State, laboratory testing performed in a physician’s office

for that clinician’s own patients is exempt from state clinical laboratory

permit requirements. However, the federal Clinical Laboratory Improve -

ment Amendments of 1988 require that all entities performing laboratory

procedures register with the federal Centers for Medicare and Medicaid

Services (CMS) and adhere to quality control and assurance, testing

personnel, record keeping and other technical requirements.

Wadsworth Center provides certification of these facilities through the

Physician Office Laboratory Evaluation Program, under contract to the CMS.

BREATH AND BLOOD ALCOHOL TESTING

This program permits individuals to perform blood and breath alcohol

analysis, ensures training agencies fulfill the necessary requirements

and approves breath alcohol instruments and ignition interlock devices.

REGULATED MEDICAL WASTE

The Regulated Medical Waste Program ensures the proper handling,

storage and treatment of regulated medical waste in hospitals

and clinical laboratories. The program also reviews and approves

manufacturers’ applications for the use of new alternative regulated

waste treatment systems.

LABORATORY INVESTIGATIONS

This unit handles and investigates complaints issued against regulated

parties, works closely with the regulatory programs to perform on-site

investigations and prepares referrals for administrative actions to the

Health Department’s Division of Legal Affairs.

32

CORE FACILITIES

Core facilities provide scientific staff with access to shared instrumentation, services and

expertise that would normally be beyond the fiscal means of an individual investigator or program.

Thus, core facilities eliminate needless duplication of high-end analytical equipment and

specialized personnel services. Wadsworth Center’s cores are grouped into three general themes:

IMAGING

Advanced Light Microscopy and Electron Microscopy, including various modes of image analysis

BIOCHEMISTRY, IMMUNOLOGY AND HISTOPATHOLOGY

Biochemistry Instrumentation, Flow Cytometry and Nuclear Magnetic Resonance Spectroscopy,

and Histopathology

GENOMICS AND BIOINFORMATICS

DNA Sequencing, including Next-Generation Sequencing, Genotyping and Bioinformatics

EDUCATIONAL PROGRAMS

Wadsworth Center houses the University at Albany, School of Public Health’s Departments of

Biomedical Sciences and Environmental Health Sciences. Master’s and doctoral degree students

prepare for teaching, research and technical careers in academia, government and industry.

In addition, Wadsworth Center offers its own Master of Science Degree in Laboratory Sciences,

and hosts a summer program for undergraduate students.

EXTRAMURAL FUNDING

Wadsworth Center administers legislatively authorized extramural funding programs that support

New York State investigators studying specific topics, including:

BREAST CANCER

The Health Research Science Board supports breast cancer research and education.

MULTIPLE SCLEROSIS

The New York State Multiple Sclerosis Research Fund supports scientific research into

the causes and/or treatment of multiple sclerosis.

SPINAL CORD INJURIES

The Spinal Cord Injury Research Board distributes research awards to find a cure for

spinal cord injuries.

STEM CELLS

The Empire State Stem Cell Board makes awards in fields related to stem cell biology.

HEALTH RESEARCH, INC.

Health Research, Inc. (HRI), a 501(c)(3) not-for-profit corporation affiliated with the

Department of Health, administers external grant support received by Wadsworth Center

investigators and disseminates the benefits of the laboratory’s expertise through programs

such as technology transfer.

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Wadsworth CenterNYS Department of HealthEmpire State PlazaP.O. Box 509Albany, New York 12201www.wadsworth.org