NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 26 ISSUE 1 • JANUARY-FEBRUARY 2018

Immunotherapy Higher Brain Glucose Levels May Mean More- Pioneer Tells All Severe Alzheimer Disease Steven A. Rosenberg, M.D., Ph.D. BY EMILY PETRUS, NINDS

S t e v e n R o s e n b e r g i s w i d e ly considered the father of cancer immunotherapy. His 40-year scientific journey has led to an explosion of immunotherapy treatments for numerous cancer types both at the NIH and across the globe. His journey began when he witnessed one of the rarest events in medicine—the spontaneous regression of a tumor. Early in his career, he had encountered a young man whose cancer had disappeared. Rosenberg, who’s now the chief of surgery in the National Cancer Institute (NCI), believed that the answer had to lie in the patient’s own immune system. Rosenberg started his pioneering work on immunotherapy in the late 1970s when almost nothing was known about T NIA lymphocyte function in cancer and there was no convincing evidence that any immune NIH scientists found potential connections between problems with how the brain processes glucose and Alzheimer disease: glucose processed normally (red); glucose processed poorly (blue) so there’s excess in some areas of the brain. reaction existed in patients against their cancer. Shortly after the description of a scientists have found a connection between abnormalities in how the brain T-cell growth factor now called interleukin breaks down glucose and the severity of the signature amyloid plaques and tangles in the 2 (IL-2), Rosenberg began studies of the brain, as well as the onset of eventual outward symptoms, of Alzheimer disease. The study ability of IL-2 to generate cells with anti- was led by researchers at the National Institute on Aging. cancer activity in the laboratory and in READ MORE ABOUT THIS AND OTHER RESEARCH BRIEFS ON PAGE 8 tumor-bearing mice. In a series of clinical trials based on these findings, he injected IL-2 or cells CONTENTS grown in IL-2 into patients with advanced FEATURES • |1| Steven A. Rosenberg, M.D., Ph.D: Immunology Pioneer |1| Brain Glucose cancer who had progressed through all Levels and Alzheimer Disease |12| Nobel Laureate Roderick MacKinnon |18| 2017 Obits available therapies. In the first 66 patients DEPARTMENTS • |2| DDIR: Surveys |3| News Briefs: New NIMHD Scientific Director with metastatic cancer in whom the |4| Training: NIH Does Fitness; Data Journalism; DeMystifying Medicine CONTINUED ON PAGE 10 |6| News You Can Use: Diversity Toolkit; Fabricator; BTRIS |8| Research Briefs |13| SIG Beat |14| Colleagues: Recently Tenured |17| Abbreviations |20| Photographic Moment: Flu Vaccine FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

Of Assays and Surveys: Tools to Inform Decision-Making BY MICHAEL GOTTESMAN, DDIR

For basic scientists and clinicians, that we send broadly to NIH staff if you • Recently, the Assembly of reproducible, accurate, and sensitive promise to respond to the best of your Scientists sent out a survey asking its assays are the gold standard for ability to those surveys we do send out. constituents to comment on the relative evaluating homogenous populations importance of many of the challenges of molecules. For social scientists Let me illustrate the importance of this faced by scientists at the NIH. The and administrative decision-makers, request with a few examples: responses will be used to limit, insofar surveys are the gold standard • Each year the federal government as possible, some of the administration for evaluating information from asks you to fill out the Federal Employees burdens faced by our scientific and heterogeneous populations of people. Viewpoint Survey (FEVS). The survey clinical investigators. Assays can yield accurate data based results help us determine whether work • Under the direction of the on a relatively small sample of conditions at the NIH match your Women Scientists Advisors, a survey homogeneous molecules. was created to assess Surveys, however, can only the experiences of yield useful data if they are At the NIH we make decisions at our postdoctoral based on larger samples of all levels that profoundly affect the fellows. The fellows heterogeneous populations. will fill out the Biostatisticians tell organization’s mission and the conduct survey when they us that a 10 percent truly of science here. We need to have input check out through random sample is a good the Foundation representation of the from all our NIH workforce to make for Advanced response of an entire large informed decisions. Education in the population. The problem Sciences (FAES). is that it is very difficult to The results will help achieve random samples in all substrata expectations and, more specifically, us understand the factors affecting of a large population. So we must rely on identifies areas in need of remediation. career decisions by our fellows. a high response rate in order to obtain For example, several years ago, the FEVS meaningful information to inform results emphasized the need for programs I am well aware that some of the decision-making. that increase work-life balance (such as surveys are complex and lengthy (in This argument is not purely theoretical. flexible work hours and telework). In some cases this approach is needed to At the NIH we make decisions at all levels consequence, NIH now has a very robust verify the statistical accuracy of the that profoundly affect the organization’s program in these areas. responses), but we cannot get an overall mission and the conduct of science here. • The NIH is assembling an view of your circumstances unless We need to have input from all our NIH important survey on workplace climate everyone is willing to take some time workforce to make informed decisions. and harassment, including sexual to complete the surveys. The result will One of the ways to obtain such input is harassment. You will receive it later this be more informed decision-making and through surveys. But all too often, staff winter or early spring. The results will more effective NIH management. either ignore the surveys we send or have a profound impact on the programs cannot find time to respond to them. I we develop to ameliorate unacceptable As always, your comments will be will promise to limit the number of surveys situations. Please participate fully. appreciated.

2 THE NIH CATALYST JANUARY-FEBRUARY 2018 NEWS BRIEFS

New NIMHD Scientific Director: Anna María Nápoles, Ph.D., M.P.H. Nápoles Is NIH’s First Latina Scientific Director

health disparities research has become a at NIMHD. In addition, she will continue recognized scientific field of study. her own research—using lay health workers Nápoles has been at the forefront of and mobile health applications—on developing methods for an underserved the effectiveness of stress management community to be engaged in translational and physical activity interventions for research to improve its own health. Her underserved cancer patients. work involves building the capacity for Nápoles holds a bachelor’s degree the community to deliver culturally in psychology from Pomona College suitable, evidence-based, behavioral (Claremont, California) and a master’s in interventions. She brings more than 25 public health and a Ph.D. in epidemiology years of experience in research on patient- from the University of California at Berkeley clinician communication, cancer-control (Berkeley, California). In 2003 and 2005, she health disparities, psycho-oncology, and received the Rising Star in Cancer Research community-based models of research in Award from the Redes En Acción Network, racially, ethnically, and socioeconomically and she is a 2016 Susan G. Komen Scholar. diverse populations. She has served as a

EDGAR DEWS III, NIMHD scientific advisor to many NIH- and non- Anna María Nápoles, who was a professor and behavioral NIH-funded research projects, advising IRP WEBPAGE epidemiologist at the University of California at San Francisco, on the use of advanced qualitative and was recently appointed scientific director for the National Highlights of what you’ll find on the Institute on Minority Health and Health Disparities. quantitative methods for studying complex sociobehavioral processes that affect the Intramural Research Program (IRP) health of underserved populations. After webpage (https://irp.nih.gov) The National Institute on Minority NIH conducted an extensive national search • Research resources: https://irp.nih.gov/ Health and Health Disparities (NIMHD) for this appointment, Nápoles began her our-research/research-resources announced the appointment of Anna appointment on November 13, 2017. María Nápoles as the scientific director “Her breadth of knowledge and notable • Principal Investigators: https://irp.nih. (SD) of its Division of Intramural Research, scientific contributions are exactly what gov/our-research/principal-investigators making her the first Latina named to NIMHD needs to meet the challenges • Accomplishments: https://irp.nih.gov/ an SD position at NIH. Before coming of the ever-evolving health-disparities accomplishments to NIH, Nápoles was a professor and environment for all racial and ethnic behavioral epidemiologist in the Division minorities,” said NIMHD Director Eliseo • Research in Action: https://irp.nih.gov/ of General Internal Medicine, Department J. Pérez-Stable. “Anna is the embodiment our-research/research-in-action of Medicine, at the University of California of one of the NIMHD intramural research • Hot Papers: https://irp.nih.gov/ at San Francisco (San Francisco), where she program’s major objectives, which is to add news-and-events/hot-papers worked from 2001 until her move to NIH. to the diversity of individuals and research NIMHD supports intramural and disciplines in the NIH intramural program.” • “I Am Intramural” Blog: https://irp.nih. extramural research on minority health In her new role, Nápoles is using gov/blog and health disparities. One of the greatest the robust basic-science environment at • Careers: https://irp.nih.gov/careers challenges is reducing the profound disparity NIH to focus on population health with in the health status of the country’s racial an emphasis on social, behavioral, and • Research Training: https://irp.nih.gov/ and ethnic minority, rural, low-income, and clinical research. She will also oversee the research-training other underserved populations. Through the executive direction and scientific leadership • And much more NIMHD’s leadership, over the past decade, for the entire intramural research program

https://irp.nih.gov/catalyst 3 THE TRAINING PAGE

From the Fellows Committee NIH Does Fitness BY CRAIG MYRUM, NIA

Being a trainee can be tough at Make your fitness goals S.M.A.R.T.! times. We need to be able to balance an S.M.A.R.T. means your fitness goals should overwhelming number of tasks including be specific, measurable, attainable, relevant, lab meetings, research, writing, keeping and timely. up to date with the literature, mentoring, • Specific: Your goals should be clear teaching, and attending conferences. and easy to understand. A common goal is While we know that time for fitness and to “get healthy” such as starting an exercise wellbeing should be prioritized, they are program, stopping smoking and losing often the first to fall by the wayside when weight. time is limited. To help you with that, • Measurable: A goal to “lose weight” the NIH “takes its own best advice” by is not enough. How you track your weight turning to a fitness and wellbeing program loss is measureable such as losing one pound to promote and cultivate health, happiness, per week.

and productivity across its campuses. IMAGES/THINKSTOCK.COM TONGRO • Attainable: Goals should be set high, Fitness and wellbeing can be many but they must also be realistic. For example, things to different people, so you should opportunities also exist at the NIH to if you are new to running, having a goal to choose activities that work for you. “You cultivate a more holistic view of wellness. run a marathon in two months will set you should always make sure your fitness For example, the Office of Intramural up for failure and pain. activities are fun!” said Shuntrice Training and Education’s Mindfulness • Relevant: Set goals that are important Holloman, program specialist for the NIH Meditation Group offers two hour-long to where you are currently. Do not set a goal Fitness and Wellbeing Program. “You can weekly drop-in sessions for novices and that someone else is pressuring you attain. do fun activities like taking a dance class, experts alike to slow down and connect • Time-bound: Make sure each goal hiking, [or] bowling. If you’re not enjoying with yourself (https://www.training.nih. has a specific time frame for completion. your physical activity, it is likely you will gov/mindfulness_meditation_group). These This allows you to easily determine if your be inconsistent.” sessions are gaining in popularity. goal has been achieved. For busy individuals looking for an At the NIH campus in Baltimore, opportunity to participate in fitness activities postbaccalaureate fellow Kevin Stieger “Fellows may not be aware of the wide at NIH, the Recreation and Welfare recently established a mindfulness range of fitness and wellbeing activities we (R&W) Fitness Center offers free “Fitness meditation group. Like many of us, offer to NIH staff,” said Holloman. “It is for You” classes monthly. The Fitness Center Stieger felt anxious and overwhelmed one of our goals to bring more awareness can bring customized fitness classes to your in college. “I didn’t really know what to our program and services.” organization based on what would be a mindful meditation was, but I thought Be creative this New Year! Try a good fit for your office. In addition, the I wanted to try it out,” he said. “Through free “Fitness for You” class or any other Fitness and Wellbeing Program partners meditation, I’ve since gotten better at wellbeing activities offered at NIH. with institutes and centers to promote recognizing negative emotions like Remember fitness and wellbeing should other wellness and fitness activities. For anxiety and stress. Instead of reacting and be tailored and relevant to your goals. example, in September, The Fitness and letting them take over, I can experience Wellbeing Program partnered with the them as a feeling and let them pass. For more information, visit https://well- National Center for Complementary and My goal is for people to come by and nessatnih.nih.gov/Pages/default.aspx. To Integrative Health (NCCIH) to observe learn the basic principles of mindfulness join the NIH Wellness LISTSERV and get “National Yoga Month” through lectures meditation so that they too can start their updates on upcoming activities and fitness and yoga sessions. own practice and have a group to discuss tips, go to https://list.nih.gov/cgi-bin/ Besides physical wellbeing, their experiences.” wa.exe?A0=wellnessnih.

4 THE NIH CATALYST JANUARY-FEBRUARY 2018 THE TRAINING PAGE

Special to the Training Page DEMYSTIFYING MEDICINE

Getting the Best of Both Worlds with Data Journalism Tuesdays, Jan. 9–May 8, 2018, 4:00–5:30 p.m. BY HUSSAIN ATHER, NIDDK Conf. Rm. 1227, Building 50 (unless noted otherwise) states—California, Texas, New York, Videocast live and archived online at https:// and Florida—against the company’s videocast.nih.gov/default.asp. records of payments to doctors and To sign up and for more information, go to medical researchers. For another article, https://demystifyingmedicine.od.nih.gov. R helped him illustrate the pervasiveness of infectious diseases in lower-income Partial schedule: countries. R has also been used to create January 9: “New Viral Diseases, Universal graphics to visualize life expectancy at Vaccines, and Removing Agents from the birth and gross domestic product per IVARY/THINKSTOCK.COM Blood Supply” (Anthony S. Fauci, MD, NIAID; capita to understand disparities among Robert Allison, MD, MPH, CC) countries or regions of the world. January 16: “Is Leukemia Curable?” (Terry He taught us about analyzing different Frey, MD, NCI; Nirali Shah, MD, NCI) It’s great when you find an file types, installing software packages, January 23: “Sexually Transmitted Diseases: opportunity that provides the best of making graphics, and exporting files. Situation Getting Worse…and Also Better” both worlds. As a postbaccalaureate He explained the technical specifics and (Thomas Quinn, MD, NIAID/Johns Hopkins researcher at NIH, I work with big jargon of the computer-science world in a Bloomberg School of Public Health; Douglas data. I’m also a writer in my spare time. way anyone could understand. Aldhous Lowy, MD, NCI) Last fall, I attended the 2017 World also talked about using data to create January 30: “Why Is HIV Still a Biologic and Conference of Science Journalists in San maps to visualize the damage done by Epidemiologic Challenge Worldwide?” (John Francisco and discovered the perfect Hurricane Harvey, the path of the August Coffin, PhD, Tufts/NCI; John Mellors, MD, way to explore both of my interests: 2017 solar eclipse, and nationwide access University of Pittsburgh) data journalism. It involves the finding, to health care. February 6: “The New Frontier: Immunother- collecting, and analyzing of data to We even practiced using R and apy of Cancer” (James Gulley, MD, PhD, NCI; create compelling news stories. constructing graphs to visualize trends. James Hodges, PhD, MBA, NCI) *Lecture will At the conference, I attended a With my experience in programming, I be held in Building 1, Wilson Hall workshop on “Data Journalism in R” (R found the workshop projects relatively February 13: “Does Inflammation Cause is a programming language), which was easy to complete. When I realized the Cardiovascular Disease? If So, How?” (Alan led by science writer and BuzzFeed News similarities between the work of data Remaley, MD, PhD, NHLBI; Nehal Mehta, MD, reporter Peter Aldhous. He also teaches journalists and that of data scientists, I NHLBI) journalism courses at the University of was surprised at how much my scientific February 20: “The Microbiome in Man, California, Santa Cruz (Santa Cruz, skill set of programming could translate Animals, and Disease: Where Do We Stand?” California) and the University of into another field such as journalism. (Yasmine Belkaid, PhD, NIAID; Barbara California, Berkeley (Berkeley, California) The workshop gave me a new Rehermann, MD, NIDDK) and his work has included machine appreciation for science writing. The way February 27: “The Great Neglected Diseases” learning, mapping, data visualization, writers like Aldhous can take advantage (Alan Sher, PhD, NIAID; Thomas Nutman, MD, and processing geographic data. of statistics, network analyses, and other NIAID) Aldous described how he has used resources helped me realize how science March 6: “Diabetes and Artificial Sweeteners” the popular open-access programming writers can take advantage of whatever (Phillip Gorden, MD, NIDDK; Kristina Rother, language, R, to analyze data for his they have available to them in crafting MD, NIDDK) stories. For example, in his 2010 New stories. From the nuance of each graph March 13: “Brave New World: Imaging from Scientist article on a pharmaceutical to the overall idea of each story, data the Cosmos to the Molecule” (John Mather, company’s payments to censured doctors, journalists understand how to get their PhD, NASA; Jennifer Lippincott-Schwartz, he used R to match doctors in four messages across. PhD, MS, HHMI, Janelia Research Campus)

https://irp.nih.gov/catalyst 5 NEWS YOU CAN USE

NIH Develops Toolkit for Enhancing Scientific Workforce Diversity BY ALISON DAVIS, OD

NIH staff can learn about this strategy by using a free, downloadable interactive toolkit. Through text-based information, informative weblinks, video, and an extensive citation library, the toolkit provides users with evidence- based interrelated activities developed and implemented by SWD. These include methods to expand diversity of candidate pools, proactive outreach approaches, strategies for mitigating bias in search processes, and tips on developing and sustaining mentoring relationships. The toolkit details a search recruitment protocol developed by SWD in concert with the NIH library. This protocol guides users through readily available online search techniques and proactive outreach approaches that broaden and deepen candidate pools. Also central to enhancing diversity Workforce diversity is important experiences and in scientific interest. is understanding, and mitigating, the for many reasons, one of which is to Yet the country’s scientific workforce impact of implicit bias throughout engage diverse perspectives in creating and NIH still lack diversity, especially the process of identifying and hiring practical solutions, without which we at the level of faculty, thus limiting our scientific talent. The SWD toolkit can encounter serious problems. potential for innovation and relevance. describes multiple ways to approach For example, when YouTube’s almost Fortunately—according to the National this sociocultural issue that is common entirely right-handed developer team Science Foundation survey of earned across sectors and not limited to science built an iOS app without considering doctorates—the pool of scientists and medicine. how left-handed people would use it, from diverse backgrounds has grown Finally, toward addressing as many as 10 percent of videos were substantially over the past few decades: inclusion—a key factor for retaining uploaded upside down! The number of biomedicine-relevant talent—the toolkit presents an up-to- Diversity promotes increased scrutiny Ph.D.s earned by individuals from date view of the value of fostering of a problem, opening the door to a underrepresented groups has increased mentoring relationships. Strategies multitude of solutions made possible by about 60 percent since 1996. and resources presented go beyond the by a heterogeneity of experiences. The NIH Scientific Workforce traditional mentor-mentee dyad and Workforce diversity contributes Diversity (SWD) office has created have been proven to enhance career directly to problem solving by inviting an integrative strategy for enhancing satisfaction and productivity. varied thoughts, experiences, and scientific workforce diversity that will abilities. Research shows that such help NIH institutes and centers to For more information and to download the cognitive diversity may not only reflect identify, recruit, and advance scientists toolkit, visit https://diversity.nih.gov, or racial, ethnic, and gender diversity but from underrepresented groups ready to contact [email protected]. also differences in geographic and life pursue today’s biomedical challenges.

6 THE NIH CATALYST JANUARY-FEBRUARY 2018 NEWS YOU CAN USE

Fabricators Move from ORS to ORF BTRIS BY ERIC BOCK, OD (ADAPTED FROM AN ARTICLE IN THE DECEMBER 1, 2017 NIH RECORD) BY MANJU BHASKAR, NINDS

Where do NIH scientists go when co-worker Robert Clary (now at NIH) BTRIS—the Biomedical they need custom instrumentation, helped design and build the display cases Translational Research Information equipment design, fabrication, or for the Declaration of Independence, the System—is a resource available to the modification services? For the past 35 Constitution, and the Bill of Rights at the NIH intramural community that brings years, the Mechanical Instrumentation National Archives in Washington, D.C. together clinical research data from the Design and Fabrication Branch in the These days, Metger and his co-workers Clinical Center and other NIH institutes Office of Research Services’ (ORS) help researchers, scientists, and surgeons and centers. BTRIS provides clinical Division of Scientific Equipment and design or modify metal and plastic devices. investigators with access to identifiable data Instrumentation Services (DSEIS) Often, customers come in and describe a for subjects on their own active protocols. has provided these services to campus problem to him and he finds a solution. It also gives all NIH investigators access researchers. Recently, the branch built devices that house to data without personal identifiers across On October 1, 2017, the design and animals, separate blood, and support a knee. all protocols. Data are available from 1976 fabrication services moved from ORS to The branch regularly saves researchers to the present and includes laboratory the Office of Research Facilities (ORF). money. In one instance, a scientist needed results, vital signs, radiologic reports (with DSEIS, however, will continue to provide a replacement screw for a microscope. She links to radiographic images), medication- equipment sales, rental, maintenance, and came to Metger after she learned the device’s administration data, and clinical repair services. manufacturer didn’t have any replacements. documents. BTRIS provides users with The fabricators are “experts at their The researcher would have had to buy anoth- advanced search, filtering, and aggregation craft,” said former supervisor Jerry Tyus. er microscope. Metger looked at the screw methods to create datasets to support Everything they make is a one-of-a-kind and started working. “In 10 minutes, we ongoing studies and to stimulate ideas for piece to help scientists conduct experiments saved NIH $20,000,” he explained. new research. Also, many types of reports and contribute to innovative research. NIHers can procure fabrication services can be easily produced with a user-friendly One of the fabricators, Howard Metger, by completing a maintenance service request series of prompts. has worked there since 2004. Before that, online or by phone. For more information, Under the leadership of Jose Galvez, he was with the Department of Defense visit https://www.orf.od.nih.gov/Property- who has been chief of BTRIS since July and the National Institute of Standards and Management/MaintenanceServiceRequests/ 2016, BTRIS is getting even better. He Technology (NIST). At NIST, he and his Pages/default.aspx. intends to provide access to data analysis using various tools such as programming languages R and Python in a more-secure environment. As BTRIS continues to develop, new report features data from new sources and will be added. “Our primary objective is to make BTRIS a more user-friendly interface,” said Galvez. “In the near future we will be upgrading the server to include data-analysis tools to help researchers obtain the data in desired and usable forms. We are working on data-sharing policies to make BTRIS available to extramural researchers as well.

For more information and how-to videos, visit

ERNIE BRANSON ERNIE https://btris.nih.gov. Galvez plans to revive Howard Metger is one of the fabricators who designs and customizes scientific equipment and devices. the BTRIS Scientific Interest Group soon, too.

https://irp.nih.gov/catalyst 7 CATALYTIC RESEARCH

Intramural Research Briefs

NIAID: INFECTIOUS PRION PROTEIN FOUND NIDA: SAFE FOR MOTHERS TO BREASTFEED IN SKIN OF CJD PATIENTS WHILE BEING TREATED FOR OPIOID NIAID scientists and collaborators at Case ADDICTION Western Reserve University School of Medi- Scientists at NIDA investigated the safety cine (Cleveland) have detected abnormal of breastfeeding when new mothers are prion protein in the skin of nearly two dozen taking buprenorphine, a medication used to people who died from Creutzfeldt-Jakob treat opioid addiction. Although there are

NIA disease (CJD). The scientists also exposed a many known benefits of breastfeeding for NIA: Scientists found potential connections between problems dozen healthy mice to skin extracts from two women and infants, there was little evidence with how the brain processes glucose and Alzheimer disease: of the CJD patients, and all developed prion about the concentration and activity of glucose processed normally (red); glucose processed poorly (blue) so there’s excess in some areas of the brain. disease. The study results raise questions buprenorphine in human breast milk. Using about the possible transmissibility of prion liquid chromatography–mass spectrometry, NIA: HIGHER BRAIN GLUCOSE LEVELS MAY diseases via medical procedures involv- researchers measured the concentrations MEAN MORE-SEVERE ALZHEIMER DISEASE ing skin and about whether skin samples of buprenorphine and its metabolites in For the first time, scientists have found a might be used to detect prion disease. The human breast milk and maternal plasma in 10 connection between abnormalities in how researchers stressed that the prion-seeding buprenorphine-managed mothers. In addition, the brain breaks down glucose and the potential found in skin tissue is significantly plasma samples were taken from nine infants severity of the signature amyloid plaques less than what they have found in studies when they were 14 days old. The results and tangles in the brain, as well as the onset using brain tissue. (NIAID authors: C.D. Orrú, indicated that buprenorphine concentrations of eventual outward symptoms, of Alzheimer B.R. Groveman, and B. Caughey, Sci Transl are low in the breast milk and blood of the disease. The study, led by NIA researchers, Med 9:eaam7785, 2017; DOI:10.1126/scitrans- mothers and low or undetectable in the involved looking at brain tissue samples at lmed.aam7785) breastfed infants. The study’s findings support autopsy from participants in the Baltimore the recommendation that it is safe for women Longitudinal Study of Aging (BLSA), one of NINDS, NCATS: HIBERNATING GROUND to breastfeed while maintaining buprenorphine the world’s longest-running scientific studies SQUIRRELS PROVIDE CLUES TO NEW treatments. Further study is needed, however. of human aging. STROKE TREATMENTS (NIH authors: M.J. Swortwood, A.J. Barnes, Researchers measured glucose Like people suffering from ischemic strokes, and K.B. Scheidweiler, J Hum Lact 32:675–681, concentrations in different brain regions, ground squirrels experience dramatically 2016; DOI:10.1177/0890334416663198) some of them vulnerable to Alzheimer-disease reduced blood flow to their brains when they [BY CLAIRE MCCARTHY, NCI] pathology, such as the frontal and temporal hibernate, depriving cells of life-sustaining cortex, and some that are resistant, such as oxygen and glucose. Yet the squirrels awaken NIEHS: PUTTING THE BRAKES ON the cerebellum. They analyzed three groups with no ill effects because they rev up a neu- PROTEIN PRODUCTION of BLSA participants: those with Alzheimer roprotective pathway called SUMOylation New research from NIEHS scientists symptoms during life and confirmed at death; during their extended naps. A team of NINDS suggests that intragenic enhancers, which healthy controls; and individuals without researchers and NIH-funded scientists has occur within genes rather than outside symptoms but with Alzheimer pathology recently identified a potential drug—ebselen genes, act like brakes to slow transcription found post mortem. The researchers found —that could grant the same resilience to the of the gene. The scientists showed that distinct abnormalities in glycolysis: Lower brains of ischemic-stroke patients by mim- deletion of intragenic enhancers increases rates of glycolysis and higher brain glucose icking the cellular changes that protect the the expression of the host gene and can concentrations correlated to more-severe brains of the squirrels. (NINDS authors: J.D. alter cell fate, with important implications. plaques and tangles found in the brains of Bernstock, D.Ye, Y.-J. Lee, and J.M. Hallenbeck; Enhancer mutations are associated with people with the disease. (NIA authors: Y. An, NCATS authors: A. Yasgar, J. Kouznetsova, A. many types of cancer; the research is aimed V.R. Varma, C.W. Chia, J.M. Egan, L. Ferrucci, Jadhav, W. Zheng, and A. Simeonov, FASEB J at determining whether any cancers involve and M. Thambisetty, Alzheimers Dement DOI:10.1096/fj.201700711R) the activation of a cancer-causing gene DOI:https://doi.org/10.1016/j.jalz.2017.09.011) [BY BRANDON LEVY, NINDS] due to the loss of the enhancer-mediated suppression function. Alternatively, if

8 THE NIH CATALYST JANUARY-FEBRUARY 2018 CATALYTIC RESEARCH

the protein in question prevents tumor NIBIB: RESEARCHERS growth, then having less of it may increase CREATE HIGHER- the risk of developing cancer. According QUALITY PICTURES OF to the researchers, the discovery of an BIOSPECIMENS unanticipated role for enhancers will break Researchers from NIBIB new ground in the field of transcription and and the University of alter the conventional view of enhancers as Chicago improved the

transcriptional activators. (NIEHS authors: speed, resolution, and YICONG WU, NIBIB S. Cinghu, P. Yang, J.P. Kosak, A.E. Conway, light efficiency of an D. Kumar, A.J. Oldfield, K. Adelman, and R. optical microscope Jothi, Mol Cell 68:104–117.e6, 2017) by switching from a [BY ROBIN ARNETTE, NIEHS] conventional glass coverslip to a reflective, NIBIB: In this diagram, the mirrored coverslip allows for four simultaneous views. NICHD: EXPOSURE TO AIR POLLUTION IN mirrored coverslip and (NIBIB authors: Y. Wu, A. Kumar, E. Ardiel, P. EARLY PREGNANCY MAY BE LINKED TO applying new computer algorithms to process Chandris, R. Christensen, I.N. Rey-Suarez, M. MISCARRIAGE the data. The team has spent the past few years Guo, H.D. Vishwasrao, J. Chen, and H. Shroff, Exposure to common air pollutants, such as developing optical microscopes that produce Nat Commun 8:article number 1452, 2017, ozone and fine particles, may increase the high-resolution images at very high speed. DOI:10.1038/s41467-017-01250-8) risk of early pregnancy loss, according to After the lab develops each new a study by NICHD scientists. Researchers microscope, it releases the plans and software Read longer versions of these briefs followed 501 couples attempting to for free, so any researcher can replicate the online and more at https://irp.nih.gov/ conceive between 2005 and 2009 in advances made at NIH. In 2013, the team catalyst/v26i1/research-briefs: Michigan and Texas. The investigators developed the dual-view inverted selective- estimated the couples’ exposures to ozone plane illumination microscope equipped • NIAID: Gene-Based Zika Vaccine Is Safe based on pollution concentrations in their with two lenses so it obtains two views of and Immunogenic in Healthy Adults residential communities. Of the 343 couples the sample instead of just one. In 2016, the who achieved pregnancy, 97 (28 percent) team added a third lens and showed that • NIAID: Cases of Unexplained experienced an early pregnancy loss—all this additional view can further improve light Anaphylaxis Linked to Red-Meat Allergy before 18 weeks. efficiency and resolution in 3-D imaging. • NIEHS, NIAID: Allergens Widespread in Couples with higher exposure to ozone But once three lenses were incorporated, it Largest Study of U.S. Homes were 12 percent more likely to experience became increasingly difficult to add more. The an early pregnancy loss, whereas couples researchers’ solution was conceptually simple • NIDA: Brain Pathway Involved in Drug exposed to particulate matter (small and relatively low-cost. Instead of trying to Relapse particles and droplets in the air) were find ways to stuff in more lenses, they use • NIDA: Brain Networks Predict Drug 13 percent more likely to experience a mirrored coverslips. One complication is that Relapse with Cocaine loss. The researchers do not know why both the conventional and the reflected views exposure to air pollutants might cause contain an unwanted background generated • NIDA: Opioid-Treatment Drugs Have pregnancy loss, but it could be related to by the light source. To deal with this problem, Similar Outcomes Once Patients Initiate increased inflammation of the placenta the NIH researchers collaborated with Treatment and oxidative stress, which can impair fetal University of Chicago researchers, who helped • NICHD, NCI: Obesity During Pregnancy development. More research is needed to create computer-processing software to May Lead Directly to Fetal Overgrowth confirm this association. (NICHD authors: identify and remove the unwanted background S. Ha, R. Sundaram, G.M. Buck Louis, C. and clarify the image. The researchers hope • NIAID: Cellphone-based Microscope Can Nobles, I. Seeni, and P. Mendola, Fertil Steril that in the future this technique may be Treat River Blindness DOI:10.1016/j.fertnstert.2017.09.037) adapted to other forms of microscopy.

https://irp.nih.gov/catalyst 9 FEATURE

Rosenberg CONTINUED FROM PAGE 1 treatment was tried, there was no sign that it worked and all of these patients died of progressive cancer. Then in 1984, Rosenberg treated his 67th patient with a new regimen of high-dose IL-2 and this patient experienced a complete cancer regression that is ongoing 33 years later. These studies of IL-2 administration led to the first FDA approval of a cancer immunotherapy in patients with renal cancer in 1992 and in metastatic melanoma in 1998. “There is a possibility that an

experimental therapy is never going to RHODA BAER work,” said Rosenberg. “But when it works once then you know it’s possible.” To understand the mechanism underlying the ability of IL-2 to cause Dr. Steven Rosenberg, chief of Surgery in the National Cancer Institute, pioneered the development of the first effective immunotherapies for patients with advanced cancer. the regression of cancer in patients with metastatic melanoma, Rosenberg identified immune cells found in cancer tumors called T cells are modified to be able to identify purchased by Gilead Sciences. The company tumor infiltrating lymphocytes (TILs) that and destroy B cells expressing CD19, the can produce enough CAR T cells to treat had cancer-fighting properties. In a series of cancer is destroyed, but so is the normal 4,000 to 5,000 hospital patients per year. clinical trials, Rosenberg and his group were B-cell population. Luckily, people can live Kite replicated Rosenberg’s findings the first to show that the administration without B cells as long as they get regular in 101 patients from 22 institutions, with of these TILs extracted from a tumor and infusions of immunoglobulins. more than 40 percent of melanoma patients grown in the laboratory to large numbers The final piece of the puzzle includes experiencing complete responses—meaning could mediate tumor regression in patients wiping out the patient’s original immune all signs of cancer disappeared. with advanced melanoma. system with chemotherapy, which creates “The institutions would obtain the The second big break for immuno- an environment in which the modified T patient’s blood cells, send them to Kite therapy was Rosenberg’s discovery that T cells can be multiplied within the patient’s Pharma, [which] would introduce the cells could be genetically modified to detect body and get to work. In 2009, Rosen- anti-CD19 CAR gene, and then send and destroy cancer in patients. One type berg’s group was the first to successfully it back to the hospital’s pharmacy and of these gene-engineered cells are named treat a lymphoma patient with CAR T-cell [the CAR T cells] would get dispensed chimeric antigen receptor (CAR) T cells, therapy, and that patient remains cancer to patients,” said Rosenberg. It sounds and they were featured on the Discovery free to this day. simple, but “behind every discovery that Channel’s three-part documentary series Rosenberg’s clinic can only treat about reaches a person there’s a long history of First in Human in August 2017. For CAR six patients per month. To help more people, success and failures.” After the replication T-cell therapy to work, the T cells need to he needed to collaborate with an industry study, Kite submitted an Investigational be harvested from the patient and outfit- that could mass produce the therapy. So, in New Drug (IND) application to the FDA ted with receptors that recognize surface 2012, NCI signed a Cooperative Research in 2014, and its protocol was approved in proteins on the cancer cells. Hematological and Development Agreement (CRADA) October 2017 thus enabling the treatment cancers such as lymphoma and melanoma with Kite Pharma, a pharmaceutical com- to be applied throughout the United States. reside in B cells, which express the cluster pany founded by Rosenberg’s former NCI Rosenberg’s and NCI’s goal is to wipe of differentiation 19 (CD19) protein. When trainee Arie Belldegrun and recently out cancer. Getting the treatment to the

10 THE NIH CATALYST JANUARY-FEBRUARY 2018 FEATURE

maximum number of patients is the best corner of the NIH Clinical Center, there Rosenberg presented “Cells as Anti-cancer way to make that happen. is a long hallway with framed portraits of Drugs Entering Mainstream Oncology” at the As for the future of cancer research, the fellows he has trained over his long and 12th Annual Philip S. Chen Jr. Distinguished Rosenberg said, “We are working on productive career. Each portrait is signed Lecture on Innovation and Technology approaches now that are really exciting: and contains a sentence or two. This wall Transfer in Masur Auditorium (Building 10) cell-transfer immunotherapy for patients serves as a reminder that Rosenberg isn’t on November 17, 2017. Chen spent his career with any type of cancer.” Current FDA- curing cancer by himself but is leading a at NIH pioneering ways to deliver ideas approved immunotherapies produced by battalion of cancer warriors within and discovered at NIH to the outside world. He companies like Kite/Gilead are successful in beyond the walls of NIH. is credited with forming the NIH Office of treating only specific types of hematological What does it take to lead the NCI’s Technology Transfer and the CRADA. The cancer such as acute lymphoblastic leukemia fight against cancer, or for anybody to make recorded videocast can be viewed at https:// and lymphoma because the CAR T cells substantial progress in a complicated field? videocast.nih.gov/launch.asp?23596. can recognize molecular targets expressed Rosenberg recommends passion, but a more on a certain type of cell’s surface, such as precise label might be obsession. CD19 on B cells. But in the grand scheme “You have to be living what you’re doing, of things, epithelial solid cancers such as thinking of the problem in the shower or Read more about Steven Rosenberg esophageal, colon, and ovarian cancers when stopped at a red light; immerse your- online at account for about 90 percent of cancer self in the knowledge of a field,” he said. https://irp.nih.gov/catalyst/v26i1/ fatalities. You also have “to define the problem you’re steven-a-rosenberg-md-phd With advances in genetic sequencing, trying to solve in just one sentence, and scientists and clinicians can now appreciate pursue it with a laser-like focus.” how complicated cancer really is. Almost every cancer in every patient has a different genetic blueprint, with unique mutations recognized by the immune system. These differences explain why cancer vaccinations and other therapies to target common mutations in patients have failed: There’s

no one-size-fits-all treatment. RIGHTS CERTAIN HAS GOVT. U.S. LLC, WINSLOW TERESE © 2017 What Rosenberg’s group is doing now fits the definition of personalized medicine: Target the T cells to the mutations specific to the cancer in each individual. A patient’s tumor is run through genomic sequencing to detect all the mutations in the cancer and identify the TIL that recognize these mutations. These TILs are expanded in culture and reinfused into the patient. “We can find a way to attack the unique patient’s mutations that caused the cancer,” said Rosenberg. “It’s ironic that the mutations that caused the cancer may turn out to be the cancer’s Achilles’ heel and enable CAR T-Cell Therapy (clockwise from top left): Blood is removed from a vein to get T cells; a special receptor called a successful treatments.” chimeric antigen receptor (CAR) is made in the laboratory; the gene for CAR is inserted into the T cells; millions of CAR On the way to Rosenberg’s sizeable T cells are grown; CAR T cells are infused into the patient; and the CAR T cells bind to cancer cells and kill them.

https://irp.nih.gov/catalyst 11 FEATURE

Nobel Laureate Roderick MacKinnon: How Ion Channels Work Wednesday Afternoon Lecture Series Presentation in September 2017 BY ANNE DAVIDSON, NICHD

Listening to Nobel Laureate pore-blocking toxin to show the first Roderick MacKinnon describe how ion co-crystal structure of a potassium channel. channels function is like having Microsoft But MacKinnon’s path to Rockefeller co-founder Bill Gates explain binary code. was not an easy one. He wanted to be able MacKinnon was the opening act for the to visualize his love—the potassium ion 2017-2018 season of the NIH Director’s channel; however, when he started working Wednesday Afternoon Lecture Series on channel proteins at Harvard Medical (WALS), held on September 27, 2017, in School (Boston), the structure had not been Masur Auditorium (Building 10). solved. The pervading view in the field at MacKinnon, a John D. Rockefeller Jr. the time (1990s) and among MacKinnon’s Professor and Howard Hughes Medical own colleagues was that a structure of Investigator at The Rockefeller University ion channels was impossible to determine (New York), received the 1999 Albert because 1) they are membrane proteins; only DALE LEWIS, NCI LEWIS, DALE Lasker Basic Medical Research Award (with a few, naturally abundant membrane proteins Clay Armstrong and Bertil Hille) for “his had been characterized at that time; and 2) elucidation of the structure and function they exist in a mixture of states. of potassium channels [providing] the first So despite a lack of faith among his molecular description of an ion selective colleagues, MacKinnon left Harvard for Nobel laureate Roderick MacKinnon presented a WALS lecture on the biophysics and biology of potassium channels. channel” and the 2003 Nobel Prize in Rockefeller, where he set up a lab that chemistry (with Peter Agre) “for structural used X-ray crystallography to determine the and mechanistic studies of ion channels.” structures of ion channels. The move was (GIRK) channel, which suppresses “The love of his life [is] how ion channels a challenge: MacKinnon, who was trained electrical activity and is activated by the work,” said Anirban Banerjee during his in electrophysiology, had to transition to G protein. G proteins (guanine nucleotide- introduction of MacKinnon at the lecture. structural biology and learn crystallography. binding proteins) act as molecular switches Banerjee was MacKinnon’s postdoc at The “Rod was just stubborn and so driven by the and are involved in transmitting signals Rockefeller University in New York (2006- question,” Banerjee explained. from a variety of stimuli outside a cell 2012) and is now a principal investigator in The question driving MacKinnon’s early to its interior. MacKinnon’s lab did the National Institute of Child Health and research was how the membrane channels GIRK reconstitution in a synthetic lipid Human Development. select for potassium ions over other ions. membrane and found that four highly Ion channels are pivotal in many Using monoclonal antibodies for getting cooperative beta-gamma subunits are biological processes, such as controlling the crystals that would offer a higher-resolution needed to open the channel. pace of the heart, regulating the secretion of picture, he discovered the structure of the Recently, MacKinnon has begun hormones, and generating electrical impulses selectivity filter. delving into single-particle cryoelectron in the nervous system. Dysfunctions in There are some 80 potassium channels microscopy. This technique has allowed the channels are linked to physiological, in humans. Different channels have evolved his lab to visualize the protein Slo2, a neuronal, and other disorders. to sense different environmental stimuli: sodium-dependent potassium channel, Banerjee recalled lively lab meetings at chemical, mechanical, and electrical, which is activated under different sodium Rockefeller among MacKinnon’s graduate MacKinnon said. The channels are diverse, concentrations. students and postdocs. MacKinnon would but “what makes them a common family listen patiently and then would break in is that they all have…the selectivity filter.” To watch a videocast of MacKinnon’s WALS with a remarkably insightful soliloquy. One channel MacKinnon discussed talk, “Biophysics and Biology of K+ Channels,” Such insights were pivotal when Banerjee in the WALS lecture was the G protein held on September 27, 2017, go to https://vid- and MacKinnon successfully used a coupled inwardly rectifying potassium eocast.nih.gov/launch.asp?23487.

12 THE NIH CATALYST JANUARY-FEBRUARY 2018 THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS Free Radical Interest Group Celebration of the 30th Anniversary of the Oxygen Club BY CLAIRE MCCARTHY, NCI

NIH’s Free Radical Interest Group New Haven, Connecticut), who gave the findings indicate that EPR imaging could and the interagency and university Daniel Gilbert Memorial Lecture, described potentially be used to develop effective consortium the Oxygen Club of Greater how mitochondrial reactive oxidative species cancer treatments based on oxygen Washington, D.C., bring together a wide (ROS) play a role in aging and maternally concentrations in cancerous tissue. range of individuals who are interested in inherited deafness. He presented new Daniel Gilbert’s spirit of collegial understanding the roles that free radicals studies that indicate how mitochondrial scientific curiosity lives on as the researchers and other reactive oxygen and nitrogen stress can activate innate antiviral signaling interact with each other—via the interest species play in basic physiology, disease pathways that upregulate DNA damage- group and Oxygen Club—and continue mechanisms, and treatment strategies. resistance genes. He hypothesized that to explore the many unanswered questions The Oxygen Club, founded in 1987 by this mechanism acts as a protective signal about oxygen and free radicals. Daniel L. Gilbert (1925–2000), was the to prevent ROS-induced damage to the first group organized to study and discuss nuclear genome. The interdisciplinary nature of the NIH Free free radicals and what is now called Sonia Franco (Johns Hopkins Radical Interest Group and the Oxygen Club “oxidative stress,” in which pathogenic University School of Medicine, Baltimore), of Greater Washington, D.C., provides attend - imbalances in the body’s use of oxygen who is doing similar research, described how ees with the opportunity to both learn and occurs. On October 3, 2017, the Oxygen early, innate immune activation from DNA network. Members enjoy a spirit of informal - Club celebrated its 30th anniversary with damage is the “canary in the coal mine” that ity during seminar discussions; many produc- a symposium in Lipsett Amphitheater warns the cell of genotoxic danger. tive collaborations that transcend chemistry, (Building 10). Other presentations highlighted the biology, and medicine have begun through Gilbert was a pioneer in the field of important role that oxygen plays in cell these interactions. To receive event announce - reduction-oxygen reaction (redox) biology. death. Valerian E. Kagan (University of ments and/or to learn more, contact Michael In 1957, when he was a graduate student Pittsburgh, Pittsburgh) explained how Espey (NCI) at [email protected] or visit https:// at the University of Rochester (Rochester, oxidized lipids trigger programmed cell oir.nih.gov/sigs/free-radical-interest-group. New York), he and Rebeca Gerschman were death through interactions with metabolic the first to describe “oxygen poisoning” and enzymes. And Juliann G. Kiang (Armed link the existence of oxygen-free radicals Forces Radiobiology Research Institute, Scientific Interest Groups with damaging effects on biological systems Bethesda, Maryland) reported that blood NIH Scientific Interest Groups (SIGs) are (Science 119:623–626, 1954). Later, as an loss (which results in hypoxia) from a assemblies of scientists with common intramural researcher at the National wound after radiation injury causes more research interests. These groups engage Institute of Neurological Disorders and cell death and damage than blood loss or with their members via a listserv; sponsor Stroke, Gilbert discovered that free radiation alone. symposia, poster sessions and lectures; radicals impair communication between Another important aspect of redox offer mentoring and career guidance for nerve cells, promote neuroinflammation, biology is the development of tools to junior scientists; help researchers share the and contribute to Alzheimer disease and measure oxygen in tissue. Murali Krishna latest techniques and information; act as other disorders. His groundbreaking work Cherukuri, head of the Biophysical Section informal advisors to the Deputy Director for on oxygen toxicity laid the foundation for in NCI’s Radiation Biology Branch, Intramural Research (DDIR); provide advice many current extramural and intramural described how his lab is developing for the annual NIH Research Festival; and scientific studies. noninvasive imaging techniques based on serve as hosts for the Wednesday After- At the symposium, several people gave electron paramagnetic resonance (EPR) to noon Lecture Series. Most of these groups talks that emphasized the importance of measure oxygen concentration in tumors. welcome interested non-NIH scientists. To oxygen and free radicals in biological (Cancer patients with hypoxic tumors are learn more and see a list of the SIGS, go to processes. Gerald Shadel (Yale University, resistant to radiation therapy.) The research https://oir.nih.gov/sigs.

https://irp.nih.gov/catalyst 13 COLLEAGUES

Recently Tenured

LUCY R. FORREST, NINDS LAURA BEANE FREEMAN, MICHAIL S. LIONAKIS, NIAID ANTONINA ROLL-MECAK, JUSTIN W. TARASKA, NHLBI NCI-DCEG NINDS

LUCY R. FORREST, PH.D., NINDS communicate with their surroundings the transport of neurotransmitters such as Senior Investigator and Section Chief, by providing bridges through the lipid- serotonin, which is crucial to the function Computational Structural Biology Section, membrane barrier. of the nervous system. We also collaborate National Institute of Neurological Disorders My group is using computational and with researchers at several other institutions. and Stroke theoretical approaches to understand the We look for simple rules that underlie Education: University of Surrey, Guildford, mechanisms of membrane proteins. Of very complex biological phenomena. England (B.Sc. in computer-aided particular interest are transporter proteins, At the same time, to understand these chemistry); University of Oxford, Oxford, which capture the chemical potential energy processes at atomic detail, we apply a England (D.Phil. in biochemistry) of ionic gradients (across the membrane) range of computational tools such as Training: Postdoctoral training, Department to facilitate the movement of essential protein-structure prediction and molecular- of Physiology, the Johns Hopkins University chemicals, or unwelcome toxic compounds, dynamics simulations. More recently, we School of Medicine (Baltimore); postdoctoral into and out of the cell. A fundamental have been developing databases to capture training, Medical Research Council Dunn question is how transporters achieve the the diversity of beautiful, and functionally Human Nutrition Unit (Cambridge, required degree of specificity for a given important, patterns of symmetry that England); postdoctoral training, Center for chemical or substrate and how the protein- abound in membrane-protein structures. Computational Biology and Bioinformatics, substrate interaction is coupled to transport Columbia University (New York) ions such as sodium. A further puzzle is Before coming to NIH: Max Planck research how the transporter changes shape to allow LAURA BEANE FREEMAN, M.S., PH.D., NCI- group leader, Computational Structural access of the substrate binding sites to either DCEG Biology Group, Max Planck Institute for side of the membrane, while also preventing Senior Investigator, Occupational and Biophysics (Frankfurt, Germany) leakage. Environmental Epidemiology Branch, Came to NIH: In 2013 as a tenure-track An essential characteristic of our work Division of Cancer Epidemiology and investigator is that our hypotheses and interpretations Genetics, National Cancer Institute Selected professional activities: Reviewing are connected with experimental evidence Education: Iowa State University, Ames, Iowa editor, eLife; editorial advisory board, from biochemical, biophysical, or structural (B.S. in biology); University of Iowa, Iowa Journal of General Physiology; Faculty of studies. For example, we have long-standing City, Iowa (M.S. in preventive medicine; Ph.D. 1000 member in structural biology collaborators at Yale University (New in epidemiology) Outside interests: Hiking; sailing Haven, Conn.) with whom we have studied Training: Cancer Prevention Fellow, Division Website: https://irp.nih.gov/pi/lucy-forrest of Cancer Prevention and Occupational If you have been recently tenured, The NIH and Environmental Epidemiology Branch, Research interests: Membrane-embedded Catalyst will be in touch with you soon to NCI-DCEG; Research fellow in same branch proteins are essential components of cellular do an article about you on these pages. (2006–2009); became tenure-track organisms. The proteins allow cells to investigator in 2009

14 THE NIH CATALYST JANUARY-FEBRUARY 2018 COLLEAGUES

Came to NIH: In 2003 for training pesticides, but also exposure to livestock MICHAIL S. LIONAKIS, M.D., SC.D., NIAID Selected professional activities: Elected and poultry, diesel exhaust, endotoxins Senior Investigator and Chief, Fungal member, EPICOH Management Group; and other bioaerosols, influence cancer Pathogenesis Section, Laboratory of Clinical member, Cross-Sector Steering Council risk. There is increasing evidence that Microbiology and Immunology, National for Chronic Diseases and external co-chair early-life exposures may influence Institute of Allergy and Infectious Diseases for Cancer Agenda, National Occupational disease risk in adulthood. Therefore, I Education: University of Crete Medical Research Agenda (NORA), National Institute have initiated a study of offspring of the School, Heraklion, Greece (M.D.); University for Occupational Safety and Health; Cancer AHS participants to investigate how their of Crete, Heraklion (Sc.D.) Sub-Group chair, AGRICOH (an international childhood farm exposures may affect their Training: Rural service physician, Greek consortium of agricultural cohort studies) health in later life. Ministry of Health and Welfare (Katerini, Outside interests: Reading; traveling; In the drinking-water contaminants Greece); postdoctoral research fellow, cooking realm, previous studies have shown that Department of Infectious Diseases, Infection Website: https://irp.nih.gov/pi/ exposure to disinfection byproducts Control and Employee Health, University laura-beane-freeman (DBPs) increases the risk of bladder of Texas M. D. Anderson Cancer Center cancer. However, DBPs are a complex (Houston); internal medicine resident, Research interests: I conduct research on mixture of chemicals, so questions remain Department of Internal Medicine, Baylor several occupational and environmental about the etiologic agents responsible for College of Medicine (Houston); infectious exposures including pesticides and other the associations. Recent results from diseases clinical fellow, NIAID agricultural agents; drinking-water a case-control study suggest that in Came to NIH: In 2007 for training; became contaminants, such as disinfection addition to ingestion, exposure through assistant clinical investigator in 2010, clinical byproducts; and formaldehyde and other showering and bathing may contribute tenure-track investigator in 2012 industrial chemicals. to risk. In a large case-control study Selected professional activities: Member of In the agricultural realm, studies in the United States, we investigated several editorial boards including JCI Insight around the world have found that farmers exposure from multiple routes and found and Journal of Infectious Diseases; associate and other agricultural workers are at evidence that brominated DBPs may be editor, Frontiers in Cellular and Infection elevated risk of several specific cancers of particular concern. Microbiology; faculty member, Faculty of including Hodgkin lymphoma, non- My research with formaldehyde has 1000–Immunology, Immunity to Infections Hodgkin lymphoma, leukemia, multiple involved assessing whether occupational Outside interests: swimming; music; dancing; myeloma, and cancers of the brain, skin, exposure to formaldehyde increases the risk traveling lip, stomach, and prostate. Work-related of cancer at several sites, specifically the Website: https://irp.nih.gov/pi/ exposures suspected of contributing to respiratory tract, and whether it induces michail-lionakis the excesses include pesticides, viruses, lymphohematopoietic malignancies. We mycotoxins, and well-water contaminants. are also evaluating the biologic plausibility Research interests: Since the 1990s, I am the NCI principal investigator of formaldehyde carcinogenicity, fungal infections have emerged as a of the Agricultural Health Study particularly at sites distant from the major cause of morbidity and mortality (AHS)—a collaboration of the NCI, respiratory tract. The NCI Cohort of in immunosuppressed and critically ill the National Institute of Environmental Workers in Formaldehyde Industries is patients. The yeast genus Candida is the Health Sciences, the National Institute the largest study of occupationally exposed most common human fungal pathogen, and for Occupational Safety and Health, and workers and includes more than 25,000 the mold genus Aspergillus is the leading the Environmental Protection Agency. participants who have a median follow-up cause of infectious mortality in transplant The AHS is a prospective cohort study time of over 40 years. recipients. of approximately 90,000 participants. Our most recent follow-up on this My laboratory research focuses on 1) the The participants include licensed private study offered further insight into the cellular and molecular factors that regulate pesticide applicators and their spouses in temporality of potential associations the immune response against mucosal Iowa and North Carolina, and commercial between formaldehyde and leukemia and invasive candidiasis and invasive applicators in Iowa. We are investigating and other lymphohematopoietic how agricultural exposures including malignancies. CONTINUED ON PAGE 16

https://irp.nih.gov/catalyst 15 COLLEAGUES

Recently Tenured CONTINUED FROM PAGE 15

aspergillosis in clinically relevant animal recurrent fungal disease, we hope to discover network. Microtubules are involved models; 2) a better understanding of the novel genetic variants associated with this in biological processes throughout the genetic and immune defects that underlie susceptibility and to develop mechanism- body such as cell division, motility, and enhanced susceptibility to mucocutaneous based therapies for people affected by fungal differentiation; microtubule disturbances and invasive fungal infections in humans. infections. underlie many neurodegenerative disorders Our goal is to develop a detailed such as Alzheimer and Parkinson diseases mechanistic understanding of the molecular as well as cancer. and cellular basis of innate and adaptive ANTONINA ROLL-MECAK, PH.D., NINDS Deceptively uniform ultrastructurally, immune responses against Candida and Senior Investigator and Chief, Cell Biology microtubules are composed of multiple Aspergillus. We aim to devise novel and Biophysics Unit, National Institute of tubulin isoforms that bear a bewildering strategies to improve the diagnosis of fungal Neurological Disorders and Stroke range of post-translational modifications infections and augment or supplement Education: Albert E. Nerken School of including acetylation, detyrosination, the current antifungal drug treatment. Engineering, The Cooper Union for the phosphorylation, glutamylation, and To study host-fungal interactions, we are Advancement of Science and Art, New glycylation. Tubulin alpha and beta using in vitro cell-culture systems and York (B.E. in chemical engineering); The heterodimers consist of a compact folded clinically relevant mouse models of mucosal Rockefeller University, New York (Ph.D. in body and intrinsically disordered COOH- and systemic Candida and Aspergillus molecular biophysics) terminal tails. These tails form a dense lawn infections. Our research techniques include Training: Postdoctoral fellow, Department on the microtubule surface and serve as a variety of immunological, biological, and of Cellular and Molecular Pharmacology, binding sites for molecular motors and imaging approaches. University of California, San Francisco (San microtubule-associated proteins. The The molecular factors that mediate Francisco) majority of sequence variation and post- the immune response to candidiasis and Came to NIH: In 2010 translational modifications of tubulin aspergillosis are poorly defined. So my lab Selected professional activities: Referee isoforms concentrates on these intrinsically is investigating the molecular cues that for several journals including Journal of Cell disordered tails. Some of the modifications mediate trafficking and effector function Biology, Cell, Nature, and Science; faculty we study, such as glutamylation and of specific resident and recruited immune member, Faculty of 1000 Cell Signaling and glycylation, can add amino-acid chains that cells in antifungal host defense in vivo. Trafficking Structures Section are significantly longer than the tubulin tails We are also interested in delineating the Outside interests: Loves classical music so themselves. These modifications are thought host factors that govern fungus-specific she tries to squeeze in a concert whenever to constitute a “tubulin code” (analogous to resistance versus susceptibility at different she can; also enjoys the great museums in the histone code), which is read by cellular anatomical sites. Washington, D.C. effectors. In our clinical-research program, Website: https://irp.nih.gov/pi/ To crack the code, we first need we are investigating the mechanisms antonina-roll-mecak to understand how it is written: the of fungal susceptibility in inherited mechanism and regulation of the enzymes immunodeficiencies that lead to invasive Research interests: I am interested in that introduce tubulin-post-translational pulmonary and brain fungal infections or the morphology and dynamics of the modifications. to chronic mucocutaneous candidiasis. We microtubule cytoskeleton. Microtubules Second, we need to elucidate how post- have enrolled the world’s largest cohort of provide structural support to cells as well translational modifications and isoform patients with genetic immune disorders— as form a complex and dynamic intracellular variability affect the basic properties of deficiency of caspase recruitment-domain- “highway” that delivers molecular cargo the microtubule polymer itself. Third, we containing protein 9 and deficiency of from one end of the cell to the other. need to know how the spatial and temporal autoimmune regulator—that make them In particular, I am trying to understand patterns of microtubule modifications are susceptible to fungal infections. By using how the chemical and genetic diversity of established and propagated. corresponding gene-deficient mice and tubulin—the protein building blocks of Ultimately, we need to understand patients with susceptibility to severe or microtubules—modulates the microtubule how tubulin isoform composition and

16 THE NIH CATALYST JANUARY-FEBRUARY 2018 COLLEAGUES ABBREVIATIONS

CC: NIH Clinical Center CCR: Center for Cancer Research, NCI CIT: Center for Information Technology modifications are interpreted by the cellular Cells communicate with each other DCEG: Division of Cancer Epidemiology and effectors that regulate their recruitment or and the body by releasing proteins, Genetics, NCI DIPHR: Division of Intramural Population activity. peptides, and chemicals through a highly Health Research, NICHD To provide a mechanistic look at the regulated process called exocytosis, in FAES: Foundation for Advanced Education in the Sciences tubulin code, my laboratory has developed a which cytoplasmic cargo-loaded vesicles FARE: Fellows Award for Research Excellence biochemical platform to obtain recombinant, fuse with the cell’s plasma membrane and FelCom: Fellows Committee isotypically pure human tubulin as well release their contents. Cells go to great FDA: Food and Drug Administration as quantitatively defined, differentially lengths to ensure that exocytosis occurs FNL: Frederick National Laboratory IRP: Intramural Research Program modified tubulins. We use a variety of at precisely the right time and location HHS: U.S. Department of Health techniques to decipher the code, from and that the correct quantity and type and Human Services NCATS: National Center for Advancing structural biology and classic enzymology of materials are released. Once vesicles Translational Sciences to single-molecule biophysics, live-cell fuse, vesicle material is cleared from the NCBI: National Center for Biotechnology imaging, and modeling. plasma membrane through a coat-driven Information NCCIH: National Center for Complementary process called endocytosis, in which the and Integrative Health plasma membrane folds inward to bring NCI: National Cancer Institute JUSTIN W. TARASKA, PH.D., NHLBI substances into the cell. The primary NEI: National Eye Institute NHGRI: National Human Genome Senior Investigator, Laboratory of Cellular retrieval mechanism in eukaryotic cells Research Institute Biophysics, Biochemistry and Biophysics is clathrin-mediated endocytosis (CME). NHLBI: National Heart, Lung, and Blood Institute Center, National Heart, Lung, and Blood In CME, dozens of proteins capture, NIA: National Institute on Aging Institute polymerize, and bend a honeycomb- NIAAA: National Institute on Alcohol Education: Reed College, Portland, Ore. like coat around pieces of the plasma Abuse and Alcoholism (B.A. in biology); Vollum Institute, Oregon NIAID: National Institute of Allergy membrane to internalize material. But and Infectious Diseases Health and Science University, Portland scientists don’t yet understand how this NIAMS: National Institute of Arthritis (Ph.D. in cell biology) complex ensemble of proteins is organized. and Musculoskeletal and Skin Diseases Training: Postdoctoral training, Department NIBIB: National Institute of Biomedical In a healthy cell, the exocytosis Imaging and Bioengineering of Physiology and Biophysics, University of and endocytosis processes are carefully NICHD: Eunice Kennedy Shriver Washington (Seattle) National Institute of Child Health and balanced. Disruption of either can result Human Development Came to NIH: In 2010 in deficiencies or excesses of chemical NIDA: National Institute on Drug Abuse Selected professional activities: Editorial signals, leading to such disorders as NIDCD: National Institute on Deafness board, Journal of General Physiology; and Other Communication Disorders Parkinson and Huntington diseases, NIDCR: National Institute of Dental director, Analytical and Quantitative Light schizophrenia, epilepsy, diabetes, and Craniofacial Research Microscopy course, Marine Biological NIDDK: National Institute of Diabetes and heart and lung diseases. Not and Digestive and Kidney Diseases Laboratory (Woods Hole, Mass.); recipient of surprisingly, understanding exocytosis NIEHS: National Institute of Presidential Early Career Award for Scientists and endocytosis has been a major goal Environmental Health Sciences and Engineers (2012) NIGMS: National Institute of for the biological sciences. A gap exists General Medical Sciences Outside interests: Spending time with family; between understanding protein structures NIMH: National Institute of Mental Health drawing; aikido; running; gardening; surfing NIMHD: National Institute on Minority and their cellular contexts. We aim to Health and Health Disparities Website: https://irp.nih.gov/pi/justin-taraska fill this gap by developing and using NINDS: National Institute of imaging tools to determine the nanoscale Neurological Disorders and Stroke NINR: National Institute of Nursing Research Research interests: My lab develops structures, organization, and dynamics NLM: National Library of Medicine and uses advanced fluorescence and of molecules that are important for the OITE: Office of Intramural Training electron microscopy imaging methods biology of membrane traffic. My lab and Education OIR: Office of Intramural Research maps the fundamental architecture of to investigate the molecular organization ORS: Office of Research Services of proteins that regulate exocytosis and molecular machines to understand how ORWH: Office of Research on Women’s Health endocytosis in human cells. these complex assemblies function. OTT: Office of Technology Transfer

https://irp.nih.gov/catalyst 17 OBITUARIES

IN 2016 (NOT INCLUDED LAST YEAR) mast cells in immunological processes, began National Human Genome Research Institute’s David A. Cooney (died on October 8, 2016, at working at NIH in 1962, first as a visiting fellow Molecular Genetics Section (from 1997 until 78), who was a leading scientist in the fields in the National Heart, Lung, and Blood Institute his death). Chines was an expert in designing of pharmacology and toxicology, especially (NHLBI). He became a tenured scientist and and managing complex databases. relating to various families of anticancer eventually deputy chief in NHLBI’s Laboratory drugs, worked in the National Cancer Institute of Molecular Immunology. After formally Paul Chretien (died on August 16, 2017, at from 1964 until his retirement in 1998. retiring in 2010, he became an NIH scientist 86), a pioneer of head-and-neck tumor emeritus and continued to work full time. immunology, was an National Cancer Institute IN 2017 (NCI) senior investigator (1966–1972) and Faye Glenn Abdellah (died on February 4, Erwin Bellack (died on July 31, 2017, at 97), chief of the Tumor Immunology Section in 2017, at 97) was the founding dean of the a chemist with the Public Health Service’s NCI’s Surgery Branch (1972–1980). He was Uniformed Services University of the Health division of dental public health (1954 to among the first to characterize deficiencies in Sciences Daniel K. Inouye Graduate School 1973) was best known for his work on the T-lymphocyte function in patients with head- of Nursing and a retired rear admiral of the fluoridation of public drinking water. and-neck cancer and to compare impaired Public Health Service. In the mid-1960s, she immune reactivity in head-and-neck cancer worked in NIH’s Division of Nursing and was Robert Lewis Berger (died on July 29, to other cancer types and correlated these the first nurse and the first woman to serve 2017, at 91) worked at the National Heart, findings with treatment outcomes. as deputy surgeon general (with U.S. Surgeon Lung, and Blood Institute from 1962 to General C. Everett Koop) and was the first 1994. He studied the fast reactions of Andrew Dwyer (died on October 26, 2017, nurse to hold the rank of rear admiral. hemoglobin and its ligands in the blood, at 70) was a staff clinician in the NIH Clinical which spurred him to develop an entirely Center’s Radiology Department since 1977. Darrell Robert Abernethy (died on November new line of instrumentation that ultimately 18, 2017, at 68) served on the medical faculties had applications in other fields as well. He Rhea Moore Frazier (died on May 30, 2017, at at several universities before joining the is survived by his wife, Victoria Harden, the 69) was a program assistant in the NIH Clinical National Institute on Aging, where he directed former director of the Office of NIH History Center’s Office of Clinical Research Training a program to better understand the effects of and the Stetten Museum at NIH. and Medical Education. drugs in older patients. Kristine Lynne Buchler (died on August 31, Richard W. Hendler (died on August 8, 2017, at Calvin “Cal” Benham Baldwin Jr. (died on 2017, at 74) was a microbiologist at NIH. 90) was an accomplished biochemist who was June 28, 2017, at 91) was a founding member— part of the NIH and National Heart, Lung, and and a board member—of the NIH Alumni Carlos E. Caban (died on May 1, 2017, at 75) Blood Institute family for 48 years beginning Association and the Children’s Inn at NIH. He is retired from NIH in 2008 after 38 years of in 1952. He worked on energy-driven proton survived by his wife, Ann Baldwin Nucci, who service. He began as a research scientist and pumps and developed techniques to follow worked in NIH’s Office of Human Resources for later held administrative and program director the path of protons across cell membranes, 31 years. positions in the National Cancer Institute. which had far-reaching implications for many types of biomedical investigations. Soojay Banerjee (died on October 23, 2017, Kevin John Catt (died on October 1, 2017, Particularly important was Hendler’s at 50), a biochemist who specialized in the at 85) worked at the National Institute of development of new linear algebra–based purification of proteins for structural analysis, Child Health and Human Development mathematical techniques for isolating came to the National Institute of Neurological from 1970 until his retirement in 2012. He absolute visible and infrared spectra of Disorders and Stroke in 2005 and later moved served as chief of the Endocrinology and intermediates and better defining the kinetic to the National Cancer Institute. He played key Reproduction Research Branch, where he led sequence of events. Such insight has proven roles in the identification of the first ubiquitin an internationally recognized group working to be valuable for unraveling the kinetic steps kinase and in projects that further advanced on hormone receptors, signaling, and actions. of plaque formation in Alzheimer disease, for the field of cryoelectron microscopy. example. Peter Chines (died on July 10, 2017, at 50) Michael A. Beaven (died on April 8, 2017, at 80), was a computer scientist and database A. Everette James (died on March 14, 2017, at an expert in mast-cell biology and the roles of programmer in Francis Collins’s lab in the 78), a former visiting scientist at NCI (1991–

18 THE NIH CATALYST JANUARY-FEBRUARY 2018 OBITUARIES

1992), was chair and professor of radiological of catecholamines—a class of chemicals Disorders and Stroke’s Surgical Neurology sciences at Vanderbilt University School of that includes adrenaline, norepinephrine, Branch (1986–2007). Medicine (Nashville). and dopamine—provided the backbone for major advances in neurological and Mary Margaret Herman Rubinstein (died on Martin Katz (died on January 12, 2017, psychiatric disorders and helped bring the NIH June 9, 2017, at 81) was a neuropathology at 89) helped to establish the field of international distinction in the 1960s. researcher at the National Institute of Mental neuropsychopharmacology and was one Health (NIMH) from 1991 to 2013. She was of the first researchers to study the action Catherine D. Lewis (died on July 12, 2017) a leader in advocating for the necessity of of antidepressants on mentally ill patients. joined NIH in 1983 as a staff fellow at the using human brain material for the study He spent most of his career at the National National Institute of Diabetes and Digestive of psychiatric disorders and worked to Institute on Mental Health and was chief of its and Kidney Diseases; in 1989, she moved to the successfully expand the NIMH brain collection, clinical research branch (1968–1978). National Institute of General Medical Sciences . a forerunner of today’s Human Brain Core Collection. Amar Klar (died on March 5, 2017, at 69) Patricia Anne Martone (died on May 24, was a member of the National Cancer 2017, at 66) retired from the NIH as an Emma Shelton (died on March 29, 2017, at Institute community since 1988. His seminal administrative lab manager. 96) was among the first female scientific contributions were key in the discovery of leaders at the NIH, arriving first as a cytology gene silencing in budding yeast and fission Charles McIntosh (died on May 20, 2017, at technician in 1942. After receiving her Ph.D. yeast and the demonstration that cell-type 79), a cardiac surgeon in the U.S. Public Health in cell biology in 1949, she became a resident changes can be mediated by site-specific Service, spent 20 years at the NIH and attained biologist at the National Cancer Institute. She DNA substitutions in those organisms. He the rank of captain. He invented—and held was one of the first women to head her own was a co-discoverer of the SIR2 gene. Most several patents for—implantable heart valves. lab and conducted path-breaking research intriguing, Amar’s work demonstrated that the into the causes of cancer. two strands of DNA need not have identical Dennis L. Murphy (died on September 23, 2017, genetic properties. at 80), former chief of the National Institute of Jane E. Shure (died on April 8, 2017, at 71), Mental Health’s (NIMH) Laboratory of Clinical began at NIH in 1967 as an information intern Claude Klee (died on April 3, 2017, at 85) was Science, was known for his research exploring and became the communications director at a pioneer in the biochemistry of calcium- the neurobiology of mood and anxiety the National Institute on Aging (NIA) when it binding proteins and calcium-dependent disorders using molecular, neurochemical, was founded in 1974. signaling. Although retired for more than a and genetic techniques. He joined NIMH as a decade, she remained an active mentor and clinical fellow in 1966 and became chief of the Julius Youngner (died on April 27, 2017, at 96) advisor at the National Cancer Institute until Clinical Neuropharmacology Branch in 1977. was a world-renowned virologist best known her death. He is survived by his wife, Nancy Garrick, for his contributions to the development of who is Deputy Communications Director the first effective polio vaccine. In the 1940s, Lois Whidden Kochanski (died on January 12, at the National Institute of Arthritis and Youngner was drafted into the Army and 2017, at 93) began a 35-year career in 1970 at Musculoskeletal and Skin Diseases. selected to work on the Manhattan Project, the Foundation for Advanced Education in the studying the effects of uranium salts on Sciences (FAES) and served for many years as Edward H. Oldfield (died on September human tissue. He was serving in the U.S. its executive director until 2005. 1, 2017, at 69), a neuroscientist and Public Health Service Commissioned Corps neurosurgeon, led research programs that at the National Cancer Institute when he was Irwin Kopin (died on August 1, 2017, changed the surgical treatment of patients recruited to the University of Pittsburgh in at 88), scientist emeritus and retired with pituitary tumors in Cushing disease, with 1949 to join Jonas Salk in the quest for an scientific director in the National Institute brain and spinal cord tumors in von Hippel– effective polio vaccine. of Neurological Disorders and Stroke Lindau disease, and with spinal arteriovenous (NINDS), was a giant in catecholamine malformations. He came to NIH in 1981 as Read more online at at https://irp.nih.gov/ research at the NIH. His groundbreaking a senior staff fellow, eventually becoming catalyst/v26i1/obituaries-2017. work on the characteristics and metabolism chief of the National Institute of Neurological

https://irp.nih.gov/catalyst 19 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES FIRST-CLASS MAIL National Institutes of Health POSTAGE & FEES PAID Building 1, Room 333 DHHS/NIH MSC 0183 Permit No. G-802 Bethesda, Maryland 20892 Publication No. 18-6250

Official Business Penalty for Private Use $300

Printed on at least 20% recycled content paper and can be recycled as office white paper.

CATALYTIC REACTIONS? PHOTOGRAPHIC MOMENT

If you have a photo or Prototype for a Universal Flu Vaccine other graphic that reflects an aspect of life at NIH Colorized structure of (including laboratory life) or a prototype for a a quotation or confession that universal flu vaccine. This scientists might appreciate and nanoparticle is a hybrid that would be fit to print in of a protein scaffold (blue) the space to the right, why not with eight influenza send it via e-mail: catalyst@ hemagglutinin proteins nih.gov; fax: 301-402-4303; on its surface (yellow). or mail: The NIH Catalyst, The hemagglutinin was Building 1, Room 333. specifically engineered to display antibody-binding Also, we welcome “letters to sites common to all human the editor” for publication and influenza subtypes. The your reactions to anything on particle, designed by the Catalyst pages. Jeffrey Boyington (Vaccine Research Center, NIAID), has been shown to be an NIAID READ MORE ARTICLES, AND effective immunogen in EXPANDED VERSIONS OF THE mice and ferrets. The three- ONES IN THIS ISSUE, ONLINE AT dimensional structure of the particle was determined by cryoelectron microscopy by John https://irp.nih.gov/catalyst/v26i1 Gallagher and Audray Harris (Laboratory of Infectious Diseases, NIAID).

PUBLISHER CONTRIBUTING WRITERS EDITORIAL ADVISORY BOARD The NIH Catalyst is published MICHAEL GOTTESMAN ROBIN ARNETTE, HUSSAIN ATHER CHRISTINA ANNUNZIATA, NCI bimonthly for and by the Deputy Director for Intramural Research, OD MANJU BHASKAR DAN APPELLA, NIDDK intramural scientists at NIH. ERIC BOCK TREVOR ARCHER, NIEHS EDITOR-IN-CHIEF ANNE DAVIDSON MICHAEL ESPEY, NCI Address correspondence to: LAURA STEPHENSON CARTER Building 1, Room 333, NIH ALISON DAVIS SUSAN LEITMAN, CC EDITORS Bethesda, MD 20892 BRANDON LEVY BERNARD MOSS, NIAID JOHN I. GALLIN Ph: 301-402-1449 CLAIRE MCCARTHY HYUN PARK, NCI Associate Director for Clnical Research Fax: 301-402-4303 CRAIG MYRUM EMILY PETRUS, NINDS (FELLOW) Chief Scientific Officer, CC e-mail: [email protected] EMILY PETRUS JULIE SEGRE, NHGRI PAUL H. PLOTZ ANDY SINGLETON, NIA The NIH Catalyst online: Scientist Emeritus, NIAMS PHOTOGRAPHERS/ILLUSTRATORS GISELA STORZ, NICHD https://irp.nih.gov/catalyst WRITER-EDITOR RHODA BAER, ERNIE BRANSON RONALD SUMMERS, CC CHRISTOPHER WANJEK EDGAR DEWS III RICHARD WYATT, OIR Director of Communications, OIR IVARY/THINKSTOCK.COM WEI YANG, NIDDK DALE LEWIS COPY EDITOR TONGRO IMAGES/THINKSTOCK.COM SHAUNA ROBERTS TERESE WINSLOW, YICONG WU