NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 22 ISSUE 1 • JANUARY-FEBRUARY 2014

Crowdsourcing The Festival That Amost Wasn’t Accelerates Toxicity Testing Report From the 2013 Research Festival BY JENNIFER SARGENT, NIAMS BY LESLEY EARL, NCI

Scientists at the National Institute Neither snow, nor rain, nor for Environmental Health Sciences the gloom of a government shut- (NIEHS) have turned to crowdsourcing to down could keep NIH’s Research help analyze massive datasets and develop Festival from happening. It was just new models to predict the toxicity of phar- postponed a little. macological and environmental chemicals. Led by co-chairs Dan Kastner, Crowdsourcing involves using collective the scientific director of the National intelligence to answer a problem. The idea Human Genome Research Institute is that many hands make light work—or, in (NHGRI), and Luigi Ferrucci, the this case, that many heads make for more scientific director of the National efficient problem solving. And what better Institute on Aging (NIA), the festival way to get a scientific crowd together to served up a feast of basic science and tackle a problem than to issue a challenge? translational medicine. DARRYL LEJA, DARRYLNHGRI LEJA, It might even be right for your project. Although the festival was origi- Crowdsourcing initiatives “get the best nally scheduled for early October, the and the brightest contributing their knowl- 16-day government shutdown forced edge to get the best result,” said NIEHS the organizers to rapidly reschedule Deputy Director Rick Woychik, who helps the events for November 6 to 8 steer NIH policy for big-data challenges. instead. Most of the planned events This design represents the two 60th anniversary celebrations that In 2013, scientists at NIEHS, the took place—including the plenary the 2013 Research Festival recognized: that of the NIH Clinical Center, which opened in July 1953; and of James Watson and Francis Crick’s National Center for Advancing Transla- session, many concurrent symposia, landmark paper that first described the DNA double-helix structure, tional Sciences (NCATS), the University of and a much-anticipated Scientific published in Nature on April 25, 1953. North Carolina (UNC; Chapel Hill, N.C.), Directors Poster Session and Cook- and two nonprofits—DREAM (Dialogue off—but the Vendor Tent Show had to be rescheduled for the spring, and the National for Reverse Engineering Assessments and Graduate Student Research Conference had to be cancelled. Methods) and Sage Bionetworks (Seattle, “The silver lining, perhaps, of the shutdown was that NIH emerged as one of a very Wash.)—partnered to launch a Toxicoge- short list of government activities that everybody agreed has incredible value,” said NIH netics Challenge that asked participants to Director Francis Collins in his opening remarks at the plenary session. use genetic and cytotoxic data to develop CONTINUED ON PAGE 8 algorithms to predict the toxicity of differ- ent chemicals. Analyses such as these are CONTENTS aimed at understanding why different people FEATURES • |1| Crowdsourcing: Accelerates Toxicity Testing |1| 2013 Research Festival exposed to the same chemical in the same |3| Precision Medicine: Louis Staudt |6| Bill Gates at NIH |14| Obituaries environment display different reactions. DEPARTMENTS • |2| Guest Editorial: NIH Clinical Research Is Changing the Trajectory of Care 4| Training Page: Career Advice |5| Abbreviations |7| SIG Beat |16| Colleagues: Recently

CONTINUED ON PAGE 5 Tenured |18| Announcements |20| Photographic Moment: Doing It Right (Radiation Safety) GUEST EDITORIAL FROM THE DEPUTY DIRECTOR FOR INTRAMURAL CLINICAL RESEARCH

The NIH Intramural Clinical Research Program: Changing the Trajectory of Care BY STEVEN HOLLAND

Deputy Director for Intramural The eruption of excitement around Perhaps our greatest area of shining Research Michael Gottesman recently the dramatic and successful treatments of success is one that has been a jewel in our reviewed the profound effects that the cancer with chimeric antigen receptors has diadem for decades: our unique capacity as a NIH intramural research program (IRP) finally persuaded even the long-standing community of like-minded investigators to has wrought over the years on the current skeptics that immune control of cancer is identify specific patient phenotypes; recruit conduct of general medicine, including the real, harnessable, and effective. The deep similar patients and their families; bring use of automated blood-cell counting, vac- intramural commitment to the immune them in for study; genotype them; under- cine development, coronary imaging, pro- control of cancer by Steve Rosenberg’s lab stand the underlying mechanisms; and— tection of the blood supply, and genomic (NCI), exploring cell-mediated mechanisms, with hard work and good luck—develop new analysis. and Ira Pastan’s lab (NCI), using humoral therapies. For example, the extraordinary Following up, I wanted to highlight ones, both anticipated and facilitated this work of Marston Linehan’s group (NCI) in some ongoing intramural approaches and development. This effort to focus, train, and dissecting and defining the metabolic basis trials at the Clinical Center that promise release the latent powers of immunity on of kidney cancers has changed diagnosis, to change understanding and practice in specific tumors has emerged as one of the screening, therapy, and survival. the future. most critical and important ways in which The list of new diseases (and their genes) The treatment of patients with severe we will address cancer in the future. discovered at NIH stretches way back, but illness is special. There is a lot of anguish, Development of new tools is essential, of the pace of discovery in the past few years a lot of anxiety, and often a lot of death. It course. But just as critical is learning how to has been breathtaking: novel autoinflam- takes a special and invested commitment use the tools that already exist. Lou Staudt’s matory diseases (DIRA, NOMID); novel from all involved—patients, nurses, doctors, group (NCI) has dissected the molecular immunodeficiencies (DOCK8, PLCG2, scientists, administrators, and directors—to signature and definition of lymphomas, VPS45); novel endocrinopathies (ARMC5, sustain the conviction, momentum, and sup- enabling their detection and tailoring of NT5E, EHHADH); novel metabolic syn- port necessary to carry us through the times treatments. Staudt, Kieron Dunleavy dromes (Proteus); novel cancer syndromes that are inevitably trying and painful. But (NCI), Wyndham Wilson (NCI), and (HIF2A, GATA2); and the remarkable yield if this is where the battle lines are drawn, colleagues have honed the chemotherapy of the Undiagnosed Diseases Program led by dare we walk away? of lymphoma to a fine edge, using the NIH- Bill Gahl. All these new diseases and genes The successes of antiretroviral therapy established principles of multiagent chemo- provide even more targets for the massed for human immunodeficiency virus (HIV) therapy to achieve terrific cure rates while investigative power of NCATS, promising started at NIH originally with zidovudine reducing the need for more toxic therapies. even more new drugs for the future. (AZT); was perfected over the years with In the infectious-disease realm: While And then there’s the Julie Segre’s team infection prophylaxis, multidrug combi- working to create new drugs for tubercu- (NHGRI), which championed genome nations, and simplified delivery; and has losis, Clif Barry’s lab (NIAID) has shown sequencing to track a microbe’s spread. culminated in a widespread group of drug how to use the old drug linezolid to success- This essay presents a very brief, neces- targets and the cognate drugs that have given fully treat multidrug-resistant tuberculosis. sarily inadequate, and incomplete sampler us a new paradigm for how serious diseases Cindy Dunbar’s group (NHLBI) turned of some of the many things that are ongo- can be turned. The unconquered frontiers of eltrombopag, a drug used for severe throm- ing and outstanding in the Clinical Center’s immune reconstitution and HIV-associated bocytopenia, into a drug that can rescue intramural clinical program. What we have malignancies are slowly yielding through a significant number of people who have changed about the practice of medicine so innovative IRP studies. severe aplastic anemia. far is only the prologue.

2 THE NIH CATALYST JANUARY-FEBRUARY 2014 FEATURE

Precision Medicine Using Genomics to Get Patients the Right Treatment BY CHRIS PALMER, NCI

More than a decade and about aggressive subtype, three billion dollars were sunk into resulting in inad- sequencing the first human genome. Now, equate treatment. that feat can be accomplished in as little as Molecular tools, five days and runs about $4,000. The pro- however, can easily cess is getting quicker and cheaper by the distinguish these day. This reduction in the time and cost of subtypes so patients genomic sequencing is the foundation of can be treated personalized medicine in which genetic appropriately. “The

analysis may point to the most effective current ways that NCI RICH FOLKERS, treatments. we’re diagnosing “This is a particularly exciting time for cancer and treating us because we have tools that are just jaw- cancer are chang- dropping in their power to examine the ing before our eyes,” human genome,” Louis Staudt told the said Staudt. “We’re Louis Staudt, the director of NCI’s Center for Cancer Genomics, described how molecular audience that had gathered at Suburban moving from histo- tools can distinguish genetic differences in cancer subtypes and lead to better diagnoses Hospital on November 1, 2013, for the logical diagnosis to and treatment. first talk in the 2013–2014 Genomics in genomic diagnosis Medicine Lecture Series. as fast as we can.” therapies relies on “the distinction between Staudt, director of the National Cancer In his own research, Staudt has used molecular subtypes of cancer.” Institute’s (NCI) Center for Cancer Genom- gene-expression profiles to differentiate two Staudt predicted that “Genetic profiling ics and co-chief of NCI’s Center for Cancer previously unknown subtypes of diffuse large will become so inexpensive that patients will Research Lymphoid Malignancies Branch, B-cell lymphoma (DLBCL), which kills get it [in the] course of their standard care.” studies the molecular basis of human lym- 10,000 people in the United States annu- He envisions that one day soon, he’ll be phoid malignancies. In his talk, “Practicing ally. The two subtypes, ABC and GCB, performing more “non-clinical-trial clini- Precision Medicine in Cancer Using Genom- are characterized by elevated expression in cal trials” by crunching the genetic data ics,” he described how molecular tools that distinct subsets of genes; the ABC subtype from patient tumors—potentially millions probe DNA and RNA expression can be accumulates mutations that activate the of them—to divine detailed molecular sig- used to more accurately diagnose various B-cell receptor-signaling pathway. natures of cancer subtypes that can each be cancer subtypes and identify genetic abnor- Staudt worked with NCI colleague treated with targeted therapies. “Until we malities that can make some patients’ tumors Wyndham Wilson (NCI) to evaluate the study the great diversity of cancer,” he said, respond better to cancer-fighting drugs. B-cell signaling inhibitor ibrutinib in patients “we can’t fully appreciate its nature.” One example cited by Staudt of the with ABC DLBCL. In a pilot study con- need for accurate diagnosis comes from a ducted at the Clinical Center, they observed The Genomics in Medicine Lecture Series is a study of endometrial cancer by researchers complete and partial responses in patients collaboration of NHGRI, Suburban Hospital in The Cancer Genome Atlas project at NCI whose tumors were resistant to chemothera- (Bethesda, Md.), and Johns Hopkins University (Nature 497:67–73, 2013). The conventional py. Based on the findings, Staudt and Wilson School of Medicine. The lectures are held on the tool for diagnosing the four major subtypes led a multicenter phase 2 trial of 70 patients first Friday of the month, 8:00–9:00 a.m., in the of endometrial cancer is histological analysis, with refractory DLBCL: Patients with the lower level auditorium of Suburban Hospital. in which biopsied tissue is stained and visu- ABC subtype had a 40-percent response rate All are welcome to attend. For more informa- ally analyzed. Unfortunately, this method compared to five percent in patients with the tion, including how to watch archived videos of may result in the more aggressive serous- GCB subtype. Staudt noted that the ben- the presentations, go to http://www.genome. like subtype being misdiagnosed as a less eficial effect of ibrutinib and other targeted gov/27553517.

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

NIH CLINICAL FELLOWS DAY Career Advice from the Pros BY ERIC BOCK, CC

Persevere, learn from your mistakes, and There’s no better place than NIH to be Holland: You’re moving into an arena work with collaborators, NIH Director exposed to the cutting edge of science. where the field is vast. You’ve got to define Francis Collins told attendees at the first Holland: People joke that “NIH” stands the problem you are going to explore and annual NIH Clinical Fellows Day, held on for “Not in a Hurry” or “Nerds in Heaven.” understand that you won’t be able to master Friday, October 25, 2013. “Science doesn’t Ask yourself if you are the right nerd for it in two years. work as a lonely enterprise,” he said. “Make this heaven. Fauci: Science is more complicated today. friends, seek out mentors, and look for the The resources are constrained, but the chance to team up with others.” What were obstacles in transitioning from opportunities are unlimited. Since you Throughout the day, several other suc- a trainee to an independent physician? cannot do it all, pick out a research ques- cessful NIH physician-researchers offered Leitman: I would have liked to have had tion that is relevant and answerable. career advice, too, including Susan Leitman training in statistics, time management, and Lane: The challenge is being able to identify (CC); Marston Linehan (NCI); Elaine leadership, but NIH didn’t offer courses in the question that is relevant and [that] you Jaffe (NCI); Electron Kebebew (NCI); those when I first came here (1980s). NIH can address. Maintain focus and don’t get Steven Holland (NIAID); Anthony Fauci offers such courses now and I recommend distracted by issues you can’t control (such (NIAID); H. Clifford Lane(NIAID); and taking advantage of them. It’s also impor- as furloughs or Continuing Resolutions). Henry Masur (CC). Below is an edited tant to learn to delegate with grace, to devise Masur: Debt and attaining grants are big compilation of what they had to say: a scheme to distribute [tasks] among fellows obstacles. Develop a passion, and stick with and support staff. it as an investigator. Keep your clinical skills What is rewarding about performing both Linehan: The biggest step was deciding up-to-date so you can understand relevant research and patient care? whether I was going to tackle a question questions. Leitman: A love of science motivates us. that was substantive. Another obstacle was At NIH, we’re pushing the envelope and deciding how to focus. People were skepti- How did you apportion research time? are on the leading edge of discovery. The cal of our decision to pursue the gene for Holland: The risk is in not getting your rewards of combining research and patient kidney cancer, and it was initially difficult to research finished. Choose what you’re able care are that we move the field forward and find the right collaborators. But I persisted to do and follow it. Set your eye on why, are always learning. The ability to collabo- because my patients were dying and I didn’t and you can’t go far wrong. If you focus and rate is another benefit of academic medicine. know of a better way to help them. It took keep working, it’s hard to fail. Linehan: There’s nothing more honorable me awhile to find my niche. Linehan: The most important thing is to than taking care of patients. Having the Jaffe: For women, balancing family with understand that what you learn about sci- opportunity to pursue ideas and take care work was a challenge (in the 1970s), but ence during training is more important to of patients enabled us to make the progress today family demands are more equally you than what you work on. You’re learning we’ve made. If you are in an environment shared. The biggest obstacle at NIH is that how to think about and do science. And where you can collaborate, that’s what medi- there’s so much happening that it’s tempting read, read, read. Be the most critical person cal science should be. to go in 10 directions at once and not finish you can be. The most important person you Jaffe: You have to do what you enjoy and anything. Use your time wisely and don’t get don’t want to fool is yourself. what excites you. You have the opportunity distracted. Don’t start something new until to learn and grow from your patients. There’s you’ve finished what you’ve already begun. a unique opportunity with every patient to Kebebew: Define your career goals and The NIH Clinical Fellows Day was hosted learn something to advance science. make sure they are in line with whichever by the Clinical Center’s Office of Clinical Kebebew: What I enjoy about my work is institution you’re transferring to. Take on Research Training and Medical Education and I get to follow my nose. I wanted to make challenges and start early to look for fund- by the Foundation for the Advancement of a significant impact on peoples’ lives. At ing opportunities. Apply for eight to 10 Sciences. Read more career tips in the NIH NIH, every patient you take care of is on a grants to get a decent career-development Catalyst online at http://irp.nih.gov/catalyst/ protocol that studies an important question. award. v22i1/the-training-page.

4 THE NIH CATALYST JANUARY-FEBRUARY 2014 NIH ABBREVIATIONS FEATURE CBER: Center for Biologics Evaluation and Research, FDA Crowdsourcing CC: NIH Clinical Center CONTINUED FROM PAGE 1 CCR: Center for Cancer Research, NCI CDC: Centers for Disease Control and Prevention The Toxicogenetics Challenge was the UNC scientists. NCATS used its robotic CIT: Center for Information Technology brainchild of Raymond Tice, chief of the equipment to conduct high-throughput assays DCEG: Division of Cancer Epidemiology Biomolecular Screening Branch within the that measured the effect of eight different and Genetics, NCI FAES: Foundation for Advanced Education National Toxicology Program (an NIEHS- concentrations of adenosine triphosphate in the Sciences based interagency program for testing and (ATP). The lower the ATP concentration, FARE: Fellows Award for Research Excellence evaluating substances in the environment), the worse the cell population was growing. FelCom: Fellows Committee and Allen Dearry, director of NIEH’s Office The response was great: 34 teams sub- FDA: Food and Drug Administration of Scientific Information Management. mitted 99 entries to the first subchallenge; FNL: Frederick National Laboratory “We’re limited by our own experiences,” 24 teams submitted 85 entries to the second. IRP: Intramural Research Program HHS: U.S. Department of Health said Tice. But “there are other groups...that “The submission of so many models is and Human Services will take a novel approach and potentially a further testimony to the value of the data NCATS: National Center for Advancing Translational Sciences come up with something really exciting.” generated through our collaboration with NCCAM: National Center for “This partnership and challenge [pro- NIEHS and UNC,” said Anton Simeonov, Complementary and Alternative Medicine vide] powerful scientific insights and mean- NCATS’s acting deputy scientific direc- NCBI: National Center for Biotechnology Information ingful public-health impact by accelerating tor. The challenge “capitalized on NCATS’s NCI: National Cancer Institute the pace of toxicity testing,” Dearry added. [ability to] test thousands of chemicals, the NEI: National Eye Institute The three-month competition, which NIEHS expertise in toxicology, and the NHGRI: National Human Genome Research Institute began on June 10, 2013, comprised two sub- UNC expertise in genomics.” NHLBI: National Heart, Lung, challenges that required the development of The winning teams for both subchal- and Blood Institute computer models to predict 1) how an indi- lenges were from the Quantitative Bio- NIA: National Institute on Aging NIAAA: National Institute on Alcohol vidual’s genetics affect responses to chemical medical Research Center at the University Abuse and Alcoholism exposures and 2) chemicals’ toxicity to cells of Texas Southwestern (Dallas). They will NIAID: National Institute of Allergy and Infectious Diseases based on chemical-structure information. work with UNC and NIEHS researchers NIAMS: National Institute of Arthritis The participants had access to data from to publish their findings and algorithms in and Musculoskeletal and Skin Diseases one of the largest population-based toxicity Nature Biotechnology. NIBIB: National Institute of Biomedical Imaging and Bioengineering studies ever conducted. They tested 884 Challenges such as the Toxicogenetics NICHD: Eunice Kennedy Shriver human lymphoblastoid cell lines (from the Challenge lead to a better understanding National Institute of Child Health and Human Development NIH-led 1000 Genomes Project) that had of the relationships between chemicals and NIDA: National Institute on Drug Abuse been treated with 156 chemicals. The datasets genes, genes and pathways, and between NIDCD: National Institute on Deafness were generated by NIEHS, NCATS, and genes and diseases, said Tice. and Other Communication Disorders NIDCR: National Institute of Dental and Craniofacial Research NIDDK: National Institute of Diabetes and Digestive and Kidney Diseases NIEHS: National Institute of Environmental Health Sciences NIGMS: National Institute of General Medical Sciences NIMH: National Institute of Mental Health NIMHD: National Institute on Minority Health and Health Disparities NINDS: National Institute of Neurological Disorders and Stroke NINR: National Institute of Nursing Research NLM: National Library of Medicine OD: Office of the Director OITE: Office of Intramural Training NCATS and Education The Toxicogenetics Challenge—hosted by NIEHS, NCATS, UNC, and two nonprofits—dared the computational infor- OIR: Office of Intramural Research matics “crowd” to develop algorithms to predict the toxicity of 156 different chemicals. NCATS’s Chemical Genomics ORS: Office of Research Services Center used its Tox21 robot system to conduct high-throughput screens as part of the challenge. ORWH: Office of Research on Women’s Health OTT: Office of Technology Transfer

http://irp.nih.gov/catalyst 5 FEATURE

Bill Gates Asks NIH Scientists for Help in Saving Lives And Explains Why the Future Depends on Biomedical Innovation BY REBECCA BAKER, NIAID The Gates Foundation also focuses on providing vaccines to children in poor coun- tries. Around the time Gates and his wife, Melinda, were establishing their foundation, they were astounded to learn that 250,000 children died each year of rotavirus, a diar- rheal disease, even though a vaccine existed to prevent it. Only wealthy countries, how- ever, could afford it. The foundation wanted to make that vaccine—and others—available and affordable to poor countries, too. Vaccines for rotavirus as well as for measles, meningitis, and the pentavalent vaccine (which provides protection against BILLBRANSON diphtheria-tetanus-pertussis, hepatitis B, Microsoft co-founder Bill Gates (left) visited NIH recently to tour labs, meet with institute directors, and deliver a and Haemophilus influenzae type b) provide lecture on “Why the Future Needs Biomedical Intervention,” in which he thanked NIH for partnering with the Bill and Melinda Gates Foundation in projects that address poor health in developing countries. NIH and the Gates cost-effective and lasting protection against Foundation together provide more than half of all global-health research funding. After the talk, NIH Director disease and are key tools for saving lives. Francis Collins (right) asked Gates questions that had been posed by NIHers. “A lot of [the] rotavirus constructs were created at NIH,” Gates noted. He also “One of the makers of our modern NIH and the Gates Foundation together cited the contributions of NIH intramu- world.” A “visionary” in global health with represent 57 percent of all funding for global- ral scientists John Robbins and Rachel “the energy and perseverance … to trans- health research and development on diseases Schneerson, who developed a vaccine to form the world.” that disproportionately affect populations eradicate bacterial meningitis caused by NIH Director Francis Collins was in low-and middle-income countries: NIH Haemophilus influenzae type b. Robbins and describing Superhero … err … global-health supports 40 percent and the Foundation sup- Schneerson won the Lasker Award in 1996 philanthropist Bill Gates, who co-founded ports about 17 percent. for what the Lasker Foundation described Microsoft and the Bill and Melinda Gates “I want to thank you for your partnership as their “groundbreaking work and bold, Foundation. Gates visited NIH’s Bethes- in many things that we do together,” Gates visionary and imaginative leadership in the da campus on December 2, 2013, to tour told the crowd that had packed into Masur development and commercialization of the research labs, meet with institute directors, Auditorium. “It's a very broad partnership, Haemophilus influenzaetype b vaccine and and deliver the David E. Barmes Global touching a lot of your different institutes, bringing the vaccine to market, leading to Health Lecture, “Why the Future Needs [that] is growing over time.” the eradication of Haemophilus influenzae Biomedical Intervention.” NIH and the Gates Foundation are type b, typhoid, and pneumococcus.” The Gates Foundation, which was working together on many projects including “The effect of these vaccines is truly established in 2000 and has donated $28 determining enteric disease risk associated miraculous,” said Gates. The Gates Foun- billion for projects that include addressing with malnutrition; developing HIV and dation helps provide vaccines at tiered extreme poverty and poor health in devel- malaria vaccines as well as innovative tuber- pricing so children in poor countries can oping countries, “stands as a leader in the culosis therapeutics; assessing the population receive them at marginal costs. “Over time, fight against many of the world’s leading effects of anti-retroviral therapy to reduce the cost of making most vaccines will get causes of death and disability,” said Col- HIV transmission; developing nutritional down to something like 20 or 25 cents per lins in introducing Gates. “In fact, [it has] biomarkers; understanding iron and malaria child treated and yet it can give you lifelong transformed our approach to global health.” interactions; and more. protection.

6 THE NIH CATALYST JANUARY-FEBRUARY 2014 FEATURE THE SIG BEAT NEWS FROM AND ABOUT THE NIH SCIENTIFIC INTEREST GROUPS

New SIG: Neuron-Glia Interactions one or more dietary ingredients (including Research on brain function at a cellular vitamins, minerals, herbs or other botani- level focuses on neurons, but non-neuronal cals, amino acids, and other substances) or “To achieve the [foundation’s] ambitious cells, called glia, regulate neuronal com- their constituents; and is intended to be goals, we need your help,” Gates continued. munication and function in many ways. taken by mouth as a pill, capsule, tablet, He acknowledged that developing vaccines is All types of glial cells can detect and or liquid. The SIG will sponsor a monthly tough, especially for diseases such as human influence functional activity in neurons. seminar series and quarterly meetings, immunodeficiency virus (HIV) for which This rapidly emerging science cuts across and it will serve as a forum for discussion there is no natural immunity. Developing all traditionally separate fields of brain- of current and future activities occurring an HIV vaccine has been an important but function research at NIH. The Neuron- in the field of dietary supplements. It is elusive goal for both the foundation and Glia Interactions (NGI) SIG will bring open to everyone at NIH and associated NIH. “I’m certainly optimistic that we will together scientists investigating the rela- agencies (FDA, USDA, etc.) who share an get an HIV vaccine, although you couldn’t tionships of neurons and glia, share the interest in dietary supplements research. give a timeframe for it.” He lauded the “quite latest research on neuron-glia interactions, To join the Dietary Supplements SIG phenomenal” contributions by NIH intra- and serve as a platform for discussion and and receive notifications of meetings and mural researchers in characterizing antibod- collaboration. other events, contact Cindy Davis at davis- ies to HIV. NGI will also serve those seeking [email protected]. Another “very promising area” of information on and education about these intramural research is viral-based vaccine relationships applying to their own research constructs that convert host cells into “a on processes of development, basic biologi- factory” of disease-fighting antibodies, About Scientific Interest Groups cal functions and mechanisms, and plas- enabling “protection more rapidly than natu- at NIH ticity, in addition to diseases models and ral immunity,” Gates said. He was “thrilled” NIH Scientific Interest Groups (SIGS) pathology. To encourage mentoring and that NIH researchers “are pushing [vaccine are assemblies of scientists with common career development, postdocs and students research] forward.” research interests. These groups sponsor will have the opportunity to present their Still, Gates expressed disappoint- symposia, poster sessions, and lectures; work to the group as part of the seminar ment that U.S. funding for global health offer mentoring and career guidance for series. The NGI SIG will also host speak- is dwindling even though funding from junior scientists; help researchers share the ers from outside NIH. NGI will meet the other countries is increasing. “Investing in latest techniques and information; act as first Tuesday of every month and is open research has huge paybacks in improving the informal advisors to the Deputy Director to members of the NIH community and human condition [and] in reducing health of Intramural Research (DDIR); provide researchers in the Baltimore-Washington costs,” he said. “I am an optimist. I think advice for the annual NIH Research Fes- metropolitan area. For more information, we’ll be able to convince people that those tival; and serve as hosts for the Wednes- e-mail Amy Shafqat, [email protected]. investments should be restored and grow.” day Afternoon Lecture Series. Many of To join the LISTSERV, send your request “It’s really the kind of basic science work the SIGs are co-sponsored by neighboring to [email protected]. that you do that’s made all of this [work] academic and government institutions and possible,” Gates said. “We are just at the welcome interested non-NIH scientists. beginning of what we can do together.” New SIG: Dietary Supplements Information about group activities or new The Dietary Supplement SIG was cre- groups is published in the NIH Catalyst The annual David E. Barmes Global Health ated to bring together NIH program (http://irp.nih.gov/catalyst) and on the Lecture was established in 2001 to honor the officials and intramural investigators DDIR Web Board, which is for NIH late David Edward Barmes, an ardent and life- who are interested in dietary supple- staff only (http://www.nih.gov/ddir/ long supporter of global health, and is spon- ment research. As defined by Congress DDIR.html). Some central coordination sored by NIDCR and the Fogarty International in the 1994 Dietary Supplement Health for the groups is provided by the Office of Center. A videocast of the Gates lecture is at and Education Act, a dietary supplement Intramural Research. The complete list http://videocast.nih.gov/launch.asp?18190. is a product (other than tobacco) that is of SIGs is at http://www.nih.gov/sigs. intended to supplement the diet; contains

http://irp.nih.gov/catalyst 7 FEATURE

Research Festival CONTINUED FROM PAGE 1

This year’s festival celebrated two 60th anniversaries: James Watson and Francis Crick’s landmark paper that first described the DNA double-helix struc-

ture, published in Nature on April 25, 1953 BRANSON ERNIE (Nature 171:737–738, 1953); and the NIH Clinical Center, which was dedicated on July 2, 1953, and admitted its first patients four days later on July 6. In fact, the whole Research Festival took place in the Clini- In this year’s Research Festival, even the Scientific Directors (SDs) presented posters. Dan Kastner, Research Festival co- chair and NHGRI SD (left), won first place for his poster and for his chocolate chip cookies. Luigi Ferrucci, fellow co-chair cal Center—Masur Auditorium and in the and NIA SD (right) explained his poster to Deputy Director for Intramural Research Michael Gottesman. newly opened Foundation for Advanced Education in the Sciences (FAES) Academ- have allowed researchers to discover the infections that occurred at the NIH Clinical ic Center—instead of the Natcher Building genetic basis of rare diseases using smaller Center during 2011? In June of that year, a (Building 45), where it’s been held for years. and smaller cohorts of patients. patient colonized with the bacterium was “With the advent of whole-exome transferred to the Clinical Center; several sequencing and whole-genome sequenc- weeks after her discharge, other patients at ing, we have tools [that] allow us to take the Clinical Center were found carrying the these cohorts of relatively rare patients, or same strain of antibiotic-resistant bacteria. even small families, and crack those cases Traditional techniques for identifying in ways we weren’t able to before,” said bacteria can only broadly identify the strain. Kastner. One of the cases he highlighted Segre, however, used new techniques for involved a young child who came to the DNA sequencing to sequence the entire NIH Clinical Center with early-onset stroke genome of each patient’s infection, and

ERNIEBRANSON and fever. While the child was treated with she detected single base-pair changes. By

Cutting the ribbon to celebrate the opening of FAES’s new steroids and began to get better, it wasn’t tracing the path of infection through the space in Building 10, where the Research Festival took until years later, when another child with hospital from patient to patient, she could place: (from left to right) FAES Executive Director Chris- tina Farias; CC Director John Gallin; NIH Director Francis the same symptoms came to the Clinical help identify which additional methods were Collins; Deputy Director for Intramural Research Michael Center, that a sequencing analysis on just six needed to eliminate the bacteria from the Gottesman; and Angela Gronenborn, president of FAES individuals revealed that a single gene, with Clinical Center. “What has really driven (former senior investigator in NIDDK and now at the Uni- versity of Pittsburgh). recessive inheritance, was responsible for me into this area of research is the extent the disorder. Mutations in the same gene, encoding the adenosine deaminase protein “We really wanted to make a trans- ADA2, were later found in several more lational connection,” said Ferrucci. “We patients with similar symptoms. “I think wanted to invite the people who are in

there’s a very bright future in being able to CDC CARR, JANICE the labs—our community—to celebrate solve some of those medical mysteries,” said instances where we can translate [basic Kastner. “It allows us to . . . begin to parlay science] into human health.” that [knowledge] into targeted therapies for The plenary session featured three those patients.” talks that highlighted how the focuses of NHGRI senior investigator Julie Segre the Festival—modern translational sci- Julie Segre (NHGRI) described her team’s efforts to deter- described another medical mystery that mine the cause of antibiotic-resistant Klebsiella pneumoniae ence at the Clinical Center and the study she and other NIH intramural investiga- infections that were occurring among gravely ill, immune- of DNA—have become intertwined in 21st compromised patients in the NIH Clinical Center in 2011. tors helped solve: What was causing the This scanning-electron micrograph reveals some of the century research. The first presentation, by antibiotic-resistant Klebsiella pneumoniae ultrastructural morphologic features of the bacterium. Kastner, illustrated how new technologies

8 THE NIH CATALYST JANUARY-FEBRUARY 2014 FEATURE

to which health-care-associated infections the government shutdown and subsequent combined efforts of more than 100 trainees contribute to the public’s concern about rescheduling. in his lab over the past 20 years. seeking health care,” said Segre. “Hospital “It was [a] terrific...opportunity for people NCCAM’s scientific director Cathe- infection control, with mandatory testing, to get together again after the shutdown, to rine Bushnell highlighted changes in the is going to be crucial.” (To read more, see make scientific and other connections [at] brains of patients who suffer from chronic the November-December 2012 issue of the the NIH,” said Kastner. pain. Even Deputy Director for Intramural NIH Catalyst at http://irp.nih.gov/catalyst/ “I thought [the festival] was re-energiz- Research Michael Gottesman joined in the v20i6/intramural-detectives.) ing,” said Ferrucci. “I felt that spirit come out fun (his lab is in NCI) with a poster featur- Next it was Cynthia Dunbar’s turn to . . . the enthusiasm, of just doing the science ing the analysis of biomarkers that determine describe her own detective work. Dunbar, [and] finding and showing your results.” drug resistance in cancer cells. a senior investigator in the National Heart, It was a rare occasion for fellows to turn Lung, and Blood Institute (NHLBI), stud- To see a video of the plenary session, go to the tables on the SDs and quiz them on their ies how hematopoietic stem cells produce http://videocast.nih.gov/launch.asp?18152 scientific knowledge. Judges evaluated the cells that repopulate the immune system. For a YouTube video of Festival highlights, go posters and voted by secret ballot to deter- Her model is the rhesus macaque because its to http://youtu.be/TilycWcU_zk. mine the winner. To ensure fairness, each hematopoietic and immune systems closely of the institutes nominated a fellow to serve match that of humans. After introducing on the panel of judges. genetically “barcoded” hematopoietic stem POSTERS AND COOKIES AND SCIENTIFIC Festival goers were invited to savor a cells into the macaques, she applied high- DIRECTORS, OH MY spectacular array of homemade treats. Much throughput sequencing techniques to detect BY JENNIFER SARGENT, NIAMS of the spread was inspired by the directors’ cells derived from the original stem cells. cultural heritages, reflecting the vibrancy and One of the strengths of the She found that myeloid cells and B cells are international diversity found in labs through- intramural research program is that those closely related in the hematopoietic hierar- out NIH. In addition to many variations in leadership maintain productive labs. chy, but there is no evidence for a common of the traditional American chocolate-chip And so it was fitting that the scientific lymphoid progenitor. Most interesting were cookie, attendees were treated to a cornucopia directors (SDs) presented scientific post- her findings regarding natural killer cells, that included rugelach, Greek baklava, Italian ers at the Research Festival (and compet- which showed an ontogeny distinct from T, biscotti, Hungarian sausage, Louisiana pecan ed in a cooking competition). B, and myeloid cells. “The molecular tech- kisses, and chocolate-covered strawberries. Constantine Stratakis (NICHD) pre- niques [allow] us to approach the body like And the winners? Well, there was only sented an overview of recent advances in science fiction investigators in ways we never one: Daniel Kastner, Research Festival co- understanding Cushing syndrome, a disor- imagined would be possible,” said Dunbar. chair and scientific director of NHGRI. He der characterized by obesity and muscular After the plenary session, the Research took the prize with his poster describing weakness due to high concentrations of the Festival continued with poster sessions his group’s recent identification of a new hormone cortisol. His work represented the and concurrent symposia and, of course, autoinflammatory disease, adenosine deami- the Scientific Directors Poster Session and nase 2 deficiency, in which the deficiency Cook-off, a competition for the best poster of a protein leads to a spectrum of vascular presentation and the best home cooking. disease and systemic inflammation. And he Ferrucci “suggested the cook-off,” said won over the crowd and the judges with his Kastner. “He [said he] would prepare a BRANSON ERNIE “Butterlicious Chocolate Chip Crepes with batch of traditional Italian biscotti and Funfetti Frosting.” he threw down the gauntlet to the other scientific directors, to see [whether] they Kastner thoroughly experimented and opti- mized his methods in the kitchen. Check out could measure up to his standards of culi- NICHD Scientific Director Constantine Stratakis (left) nary excellence.” In the end, the 2013 NIH explained his poster to NHGRI Deputy Scientific Direc- the video at http://youtu.be/hjuo4D_WDdw. tor Paul Liu. Stratakis’s poster provided an overview of Research Festival weathered the bumps of recent advances in understanding Cushing syndrome.

CONTINUED ON PAGE 10

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

Research Festival CONTINUED FROM PAGE 9

PAIN, PAIN, PAIN BY ADAM J. KUSZAK, NIDDK SELECTED SYMPOSIA Increasingly, researchers across SUGAR, SUGAR NIH are tackling chronic pain in an BY ERIC BOCK, CC attempt to understand its mechanisms and how to treat or prevent it. That news When Julie Andrews sang, “Just a should come as welcome relief to the 100 spoonful of sugar makes the medicine million Americans who suffer from debili- go down” in the 1964 Disney film Mary tating, persistent pain, which may be trig- Poppins, could she have inspired budding gered by physical trauma; may be linked scientists to one day explore the thera- to arthritis, cancer, or other conditions; or peutic value of sugars? After all, the field may have no apparent cause at all.

of glycobiology, which is the study of JANICECARR, CDC Take fibromyalgia, a disorder character- complex sugar molecules, or glycans, was Flu vaccines may be improved once scientists have a ized by widespread musculoskeletal pain, launched more than 20 years after the better handle on glycobiology and glycans. Seema Lak- abnormal pain processing, fatigue, sleep dis- dawala (NIAID) is researching the role of glycans in the movie came out. Today, scientists at NIH 2009 pandemic H1N1 flu virus and found that the recep- turbances, memory problems, psychological and elsewhere hope that a better under- tor specificity of H1N1 is more complex than previously distress, and mood issues. No one knows standing of glycobiology can be leveraged thought. Shown: Transmission electron micrograph of the for sure what causes it, but it affects three H1N1 influenza virus. for therapeutic and diagnostic purposes million to six million Americans. NINR’s and may even lead to the development of Brian Walitt outlined the ailment’s history as Bordetella and Brucella. Jeffrey Gild- more effective vaccines. and discussed current debates on whether ersleeve (NCI), whose lab uses carbohy- Malfunction of a nuclear-cytoplasmic fibromyalgia is a product of disordered drate antigen microarrays to study immune signaling pathway involving the simple neural pain processing or a result of psy- responses to vaccines, has identified new glycan O-linked N-acetylglucosamine chological and cultural factors. biomarkers for predicting clinical responses (O-GlcNAc) is involved in immunity-linked NCCAM’s Scientific Director M. to cancer vaccine therapy. human diseases ranging from diabetes to Catherine Bushnell has identified one Even flu vaccines may be improved once lupus, explained John Hanover (NIDDK), effect of fibromyalgia-associated chronic scientists have a better handle on glyco- who has identified and characterized the pain on the brain: According to magnetic biology and glycans. Seema Lakdawala genes encoding the enzymes of O-GlcNAc resonance imaging studies, fibromyalgia (NIAID), who is researching the role of cycling. patients have reduced gray matter in brain glycans in the 2009 pandemic H1N1 flu The intracellular carbohydrate regions related to pain processing. Bushnell virus, found that the receptor specificity O-GlcNAc plays an important role in the has also investigated links between other of H1N1 is more complex than previously innate immune response of the nematode chronic-pain conditions and the brain. She thought. Evidence suggests that flu viruses Caenorhabditis elegans and may hold the key found that successful surgical treatment infect host cells by binding to a wide range to understanding the immune response to of chronic lower-back pain slowly reverses of acidic sugars. pathogens, according to FARE Winner brain atrophy, and long-time yoga practitio-

Michelle Bond (NIDDK). Loss of the From the 2013 Research Festival’s session ners have higher gray-matter density in pain enzymes governing the addition and “The glycobiology of immunity and infec- tolerance regions of the brain. Her work removal of O-GlcNAc triggers stress- and tion,” chaired by Pamela Marino (NIGMS), and suggests that neuroprotective approaches immune-responsive genes. held on November 8, 2013. may benefit chronic-pain patients. In the vaccine arena, Joanna Kubler- Even diet may play a role in controlling Kielb (NICHD) described the development To see a videocast of the 2013 Research chronic pain as many pain-signaling com- of vaccine candidates consisting of carbo- Festival plenary session presented on pounds are derived from dietary fats. Chris- hydrate antigens bound protein carriers in November 6, 2013, go to http://video- topher Ramsden (NIAAA) and extramural order to protect against infections caused cast.nih.gov/launch.asp?18152 colleagues conducted a clinical trial to assess by Gram-negative bacteria genera such how dietary modification could decrease

10 THE NIH CATALYST JANUARY-FEBRUARY 2014 FEATURE

the incessant pain of chronic headaches. of individual mitochondria into a tubular They hypothesized that pain signals could network, suggesting that lipid recycling and be decreased by altering dietary proportions mitochondrial function are amplified for an of omega-6 and omega-3 fatty acids. Indeed, efficient response to starvation. these dietary modifications did alter pain- Damaged mitochondria, in contrast, signaling compounds and reduce headaches. accumulate during aging and are marked The researchers are conducting a larger trial for elimination by a different self-eating pro- to expand upon these encouraging results. cess called mitophagy. This process requires New insights into the mechanisms of the parkin protein, whose gene, PARK2, is nociception (perception of pain) came from JUDITHSTOFFER mutated in some autosomal recessive forms NIDCR’s Mark Hoon and FARE Award Aging has been linked to increased obesity, declining of Parkinson disease. Chiu-Hui Huang mitochondrial function, and decreased thermogenesis, Winner Leah Pogorzala, who works in his indicating a switch from “energy-using” to “energy-storing” (NINDS) discussed her team’s new mouse lab. They are studying sensory neural cir- mode. Mitochondria (shown above) are the cells’ power model for Parkinson disease, which required plants. Damaged mitochondria accumulate during aging cuits involved in thermosensation and itch; and are marked for elimination by a self-eating process more than simply eliminating endogenous those pathways overlap with pain signaling. called mitophagy. parkin. To see Parkinson-like effects, they Pogorzala has identified neuron populations had to mimic age-dependent mitochon- that respond to hot and cold stimulation; “energy-using” to “energy-storing” mode. drial DNA damage accumulation with a Hoon explained the delineation of neuronal Reversing this energy mode through caloric second mutation in a mitochondrial DNA pathways for itch responses. Their findings restriction has been shown to extend life polymerase. are paving the way to a greater understand- span. How the cell senses and responds to Age-related decreases in mitochondria- ing of sensory and pain perception. its energy state involves the sirtuin proteins, rich, heat-producing brown fat relative to which alter chromatin organization and lipid-storing white fat is linked to the onset From the 2013 Research Festival’s session gene-expression programs. of obesity, type 2 diabetes, and other dis- “Pain and nociception: From patients to mol- Jay Chung (NHLBI) presented data orders. FARE Award winner Lingyan Xu ecules,” chaired by Mark Hoon (NIDCR), and showing a new way the mammalian sir- (NIDDK) identified a role for forkhead box held on November 6, 2013. tuin 1 (SIRT1) senses the energy status of (FOX) family transcription factors in brown the cell: It has an adenosine triphosphate versus white adipocyte balance. Xu found AGING MOLECULARLY (ATP)–dependent peptide switch that that mice deficient in the protein Foxa3 BY REBECCA BURGESS, NCI is “on” during energy depletion, whereas have increased energy expenditure and ther- excess ATP binds this switch region and mogenesis due to the “browning” of white The seemingly unstoppable pro- blocks SIRT1 activity in the “off” state. adipose tissue. These mice were protected cess of aging is the major biological risk Global chromatin organization by SIRT1 against age-related obesity and insulin factor for many chronic diseases including is also altered by DNA damage, causing resistance, suggesting that Foxa3 ablation cancer, heart disease, and type 2 diabetes. global gene-expression changes similar to could be a novel therapeutic target to treat The discovery that aging not only is an those found in aged cells. New work from aging-associated metabolic disorders. accumulation of random damage, but also Philipp Oberdoerffer (NCI) suggests that As the links between metabolism and is governed by molecular mechanisms DNA damage signals chromatin structure aging continue to emerge, the ancient Hip- that are susceptible to manipulation and to affect the way cells repair DNA damage. pocratic notion of food as medicine may intervention, suggests that trans-NIH To better understand the cellular unlock a modern fountain of youth. aging research could potentially address changes that occur upon caloric restric- multiple chronic diseases all at once. tion, Jennifer Lippincott-Schwartz From the Research Festival session “Molecular One important area in this field is cel- (NICHD) examined cell components in Mechanisms of Aging,” chaired by Felipe Sierra lular energy sensing and balance. Aging has nutrient-deprived yeast. She found that (NIA), sponsored by the GeroScience Interest been linked to increased obesity, declin- cells display an “self-eating” response, called Group, and held on November 8, 2013. ing mitochondrial function, and decreased lipophagy, which involves digesting intra- thermogenesis, indicating a switch from cellular lipids. Lipophagy requires fusion CONTINUED ON PAGE 12

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Research Festival CONTINUED FROM PAGE 11

NEUROGENETIC ANALYSIS T CELLS THROUGH OLD AGE BY MEGHAN MOTT, NIAAA BY CHRIS PALMER, NCI

New technological advances are T cells play an important role in revolutionizing our understanding of the the immune system’s response to patho- human brain and may provide clues to gens and tumor cells. However, to prevent treating, preventing, and curing brain autoimmunity, the body’s T-cell popula- disorders and diseases. NIH researchers tion must be monitored to ensure proper with expertise in genetics, physiology, development and homeostasis. Several and microscopy are collaborating to map labs at NIH investigate the molecular brain function in hopes of discovering pathways that regulate normal T-cell how neural circuits control behavior and development as well as the challenges to of determining how disruptions in brain T-cell homeostasis brought on by cancer NIH function occur in such diseases as schizo- NIH researchers are mapping brain function to determine chemotherapies and the natural aging phrenia and autism. how neural circuits control behavior and how disruptions process. in brain function occur in diseases such as schizophre- Chi-Hon Lee (NICHD) combines nia and autism. To minimize autoimmunity, T cells behavioral, imaging, and molecular genetic expressing self-reactive T-cell antigen recep- approaches to study visual circuit develop- tors (TCR) undergo programmed cell death To understand how neuronal circuits ment and function in Drosophilia. By selec- (apoptosis). Paul Love (NICHD) created develop, Tudor Badea (NEI) combines tively inactivating and restoring the synaptic knock-in mice in which TCR signaling is molecular genetics tools—conditional gene activity of different types of neurons, Lee’s significantly reduced, disrupting apopto- ablation and reporter-gene replacement— lab is dissecting color-vision circuits that sis. Surprisingly, the mice failed to develop to label individual neurons in the retina, drive color learning. Another Drosophila autoimmune diseases, leading Love and his visualize the morphology and connectivity researcher, Susan Harbison (NHLBI), colleagues to suggest the existence of a com- of specific cell populations, and study their investigates the genetic networks under- pensatory pathway for immune tolerance role in the visual system. lying sleep and their interactions with the that results in the increased development Fumihito Ono (NIAAA) wants environment. She uses high-throughput of regulatory T cells (Tregs). Xuguang Tai to answer fundamental questions about genotyping to observe heritable differences (NCI) has identified the pro-apoptotic and neuromuscular development and function. in sleep patterns and has demonstrated how pro-survival signaling mechanisms by which In particular, he uses the genetic tools of significant changes in sleep occur in just a a transcription factor called forkhead box locomotor mutants, cell-specific transgenics, few generations. She is also investigating P3 regulates the development of regulatory and a chemically inducible gene-expression how DNA polymorphisms and variation in Tregs that help prevent autoimmune disease. system to see how neuromuscular synapses transcript, protein, and metabolite concen- Nan-ping Weng (NIA) has developed form in zebrafish. trations lead to differences in sleep. a next-generation sequencing method to In other research exploring synapses, Jeffrey Smith (NINDS) uses optoge- characterize the diversity of TCRs. His FARE Award Winner Carmelo Sgobio netics to unravel the brain networks respon- group discovered that CD4 T cells have (NIA) studies presynaptic calcium modula- sible for breathing. Optogenetics involves twice as many unique TCRs as CD8 T tion in midbrain neuron terminals. He uses taking a gene for light-activated membrane cells do, and the group observed age-related tetracycline-controlled transcriptional acti- channels targeted to a single neuron type, alteration of TCR repertoire in people 45 vation to reveal how synaptic transmission at inserting it into a mouse genome, and then to 65 years old, but not in people 75 to 94 nerve terminals is mediated and regulated. shining a light into the brain to turn those years old. neurons on or off. He is also using whole- From the 2013 Research Festival session Joy Williams (NCI) reported that the cell patch-clamp recording techniques to “Neurogenetic analysis of behavioral cir- development of medullary thymic epithelial study the biophysical and synaptic properties cuits,” chaired by Harold Burgess (NICHD) cells (mTEC), which depends on the pres- of respiratory circuits in the brainstem and and Kevin Briggman (NINDS), and held on ence of a type of thymocyte—called single to explain the neurogenesis of respiratory November 7, 2013. positive (SP) thymocytes and eliminates movements. autoreactive T cells—relies on the activation

12 THE NIH CATALYST JANUARY-FEBRUARY 2014 FEATURE

of a particular pathway. When this pathway uses computational analysis to eliminate screen that identifies novel regulators of pro- is activated, mTECs can develop even in false-positive results and to identify dis- teins that mediate resistance to the chemo- the absence of SP thymocytes. ease-associated genes. His work has been therapy drug cisplatin. Hall has identified Frank Flomerfelt (NCI) discovered critical to the success of the many screen- several microRNAs and their targets that that the thymus, brain, and testes-associated ing projects the NCATS team has helped are responsible for tumors becoming resis- gene (Tbata) regulates thymic epithelial cell develop. tant to cisplatin. His group is currently fol- proliferation and thymus size by blocking a Lesley Kane (NINDS) and colleagues lowing up this work with a whole-genome pathway implicated in cell-cycle progression. are using genome-wide RNAi screening RNAi screen of protein-encoding genes. His group observed that Tbata expression to better understand the parkin-mediated The audience was also treated to a pre- increases with age and that deletion of Tbata mitochondria quality-control mechanism. sentation by FARE Award Winner Tuan results in a larger thymus later in life. Mutations in the gene PARK2, which codes Tran (NIAID). Tran described a novel Treating cancer often leads to immu- for parkin, are known to cause Parkinson method for assessing malaria risk: Looking nosuppression. FARE Award Winner Liat disease. Using a cell-based, high-content for naturally acquired antibodies specific for Izhak (NCI) studies the cross-modulation assay of parkin translocation, Kane’s group the Plasmodium falciparum parasite protein among the various immunosuppressive has identified several new genes involved in PfRH5, whose presence predicted protec- mechanisms that are driven by Tregs and this process and recently published its find- tion from malaria in a cohort of children natural killer T cells. ings in Nature (Nature 504:291–295, 2013). and adults in Mali. Another NINDS group, led by Bar- From the 2013 Research Festival’s session rington Burnett, uses genome-wide RNAi From the 2013 Research Festival’s session on “T-cell development, aging, and thymus screening to identify genetic modifiers of “Genes and pathway discovery in the context regeneration,” co-chaired by Paul Love spinal muscular atrophy (SMA). SMA is a of human diseases,” chaired by Scott Martin (NICHD) and Nan-ping Weng (NIA), and held debilitating neurological disease that leads to (NCATS) and Natasha Caplen (NCI), and held on November 8, 2013. muscle weakness and wasting and is caused on November 7, 2013. by a deficiency of the survival motor neuron (SMN) protein. The screen identified a READ MORE ONLINE AT: USING RNAI TO DISCOVER GENES number of genes—including some associ- http://irp.nih.gov/catalyst/v22i1/ BY SUMAN MUKHERJEE, NIDDK ated with splicing and protein stability— the-best-research-festival-ever that affect SMN protein concentrations. Gene silencing through RNA inter- Matthew Hall (NCI) gave a presenta- Tricking Viruses into Treating Disease ference (RNAi) has become a standard tion on a microRNA functional genomic BY REBECCA G. BAKER, NIAID laboratory tool for assessing gene function, but to make the jump to discovery on a Optogenetic Manipulation of Neural Cir- large scale most intramural scientists need cuits and Behavior help. This is where the NCATS’s Trans- BY JOSEPH P. TIANO, NIDDK NIH RNAi Screening Facility comes in: Using genome-wide RNAi screening, Seriously Studying Stem Cells intramural investigators can make excit- BY ERIC BOCK, CC ing discoveries about the role of genes and pathways associated with human Breast is Still Best: Infant Dietary Guide- diseases. Scott Martin, the leader of the lines Get an Update for the 21st Century

Trans-NIH RNAi Screening Facility, NCATS CARLEENKLUMPP, BY REBECCA BURGESS, NCI outlined how his team goes about helping Gene silencing through RNA interference (RNAi) has become intramural scientists to develop and per- a standard laboratory tool for assessing gene function, Natural Born (Cancer) Killers but to make the jump to discovery on a large scale most form genome-wide RNAi screens. RNAi intramural scientists need help. NCATS’s Trans-NIH RNAi BY CHRIS PALMER, NCI studies on this scale also need careful Screening Facility has automated systems, like the one data analysis. Gene Buehler (NCATS) shown here, that perform genome-wide RNAi screening.

http://irp.nih.gov/catalyst 13 OBITUARIES

IN 2012 ism and depression. He served as chief of the covered a new category of lymphocytes, now psychiatry service at Edward Hines Jr. V.A. called natural killer cells. Later he studied their Benjamin T. Burton (died on December 22, Hospital outside Chicago (1976–1999). role in resistance to cancer growth. He left NIH 2012, at age 93), an NIDDK associate director for to become the founding director of the Univer- disease prevention and technology transfer, was Thomas P. Cameron (died on November 28, sity of Pittsburgh Cancer Institute. at NIH for more than 34 years. He helped develop 2013, at age 87) was a veterinarian who later protein supplements to fight malnutrition and became a captain in the U.S. Public Health Jean Hickman (died on August 26, 2013, at build new technology for kidney dialysis. Service and an official at NIH. When he retired age 89), who retired in 2008 after 57 years at in 1993, he was an assistant coordinator of NIH, was a bench scientist in the Laboratory IN 2013 NCI’s environmental carcinogenicity program. of Physical Biology in the National Institute of R. Wayne Albers (died on September 28, 2013, Arthritis and Metabolic Diseases (1951–1984). Sheldon Cohen (died March 26, 2013, at age at age 85), who came to NIH in 1954, was a After the institute split into NIDDK and NIAMS, 94) joined NIH in 1972 as a training consul- world-recognized neuroscientist noted for his she became a scientific review officer in the tant to NIAID. The following year, he became research in the field of membrane cation trans- NIAMS Extramural Program. chief of the Allergy and Immunology Branch, port and neuronal excitability. He was a former and later the director of the institute’s Immu- Daniel Hommer (died on January 2, 2013, at chief of the Section on Enzyme Chemistry in nology, Allergic, and Immunologic Disease age 64) had been chief of NIAAA’s section on the NINDS Laboratory of Neurochemistry. Program (1977–1988). He continued to work at brain electrophysiology and imaging since 1992. Lynne Angerer (died on March 30, 2013, at age NIH as a scientific advisor at NIAID and as a He was world-renowned for his discoveries on 68) was chief of the developmental mechanisms visiting scholar at the National Library of Medi- structural and functional differences in brains of section in NIDCR and a world-renowned expert cine’s History of Medicine Division. alcoholic and nonalcoholic individuals. He co- in developmental biology. Using sea urchins, she directed the electrophysiology unit of NIMH’s Ricardo V. “Rick” Dreyfuss (died March 14, 2013, unraveled the core regulatory processes that Clinical Neuroscience Branch (1982–1987). at age 58) was a photomicroscopist He worked direct the early development of animal embryos. for more than 25 years—until his death—in the Juan-Teh Jeang (died on January 27, 2013, at Her husband and long-term scientific collabora- Division of Medical Arts, Office of Research Ser- age 54), a researcher at NIAID’s Laboratory of tor is NIDCR Scientific Director Bob Angerer. vices. His photomicrographs graced the covers Molecular Microbiology, studied the factors Joanne Hebb Belk (died on March 4, 2013, at of countless scientific journals. that influenced the spread of retroviruses. age 89) directed NIH’s compliance with the In 2004 he co-founded Retrovirology, which Juliana D. Franz (died on May 24, 2013, at age Freedom of Information Act (1977–1998). became the highest ranked journal in the field. 84), who practiced psychiatry in Maryland He did postdoctoral work in NCI. Costan W. Berard (died on January 5, 2013, at for more than 50 years, worked as a medical age 80) came to NCI in 1963. As chief of the officer and psychiatrist at NIMH (1953–1970). Edward J. Leonard (died on December 28, hematopathology section (1970–1980), he and 2013, at age 87), one of the early NIH clinical Emil Frei III (died on April 30, 2013, at age 89) colleagues revolutionized the treatment of fellows (1950s), retired after a 49-year career was one of the first to use combination che- malignant lymphoma and Hodgkin disease. He at NIH as director of the Immunopathology motherapy to treat cancer. He was at NCI for was chairman of the department of pathology Section in NCI’s Laboratory of Immunobiol- 10 years in the 1950s and 1960s, where he did and laboratory medicine at St. Jude Children’s ogy. Among his major accomplishments was his seminal work on chemotherapy for which Research Hospital in Memphis (1980–1997). the identification of macrophages, neutrophils, he subsequently won a Lasker award in 1972. and their chemoattractant factors. John “Jack” Bieri (died on July 30, 2013, at age Frei also held senior leadership positions at the 93) served as head of the nutritional biochem- M.D. Anderson Cancer Center (Houston) and Carol H. Letendre (died on August 22, 2013, at istry section in NIDDK’s Laboratory of Nutrition the Dana-Farber Cancer Institute (Boston). age 75), a former deputy director of NHLBI’s and Endocrinology (1955–1983). His studied the Division of Blood Diseases and Resources, Audrey Georges (died on March 6, 2013, at metabolism of vitamins A and E and essential spent 32 years at NIH, 20 of them at NHLBI. age 76) retired in 2009 as administrative lab fatty acids and developed the NIH standard diet She helped guide research that led to such manager at NEI after a 17-year career at NIH. for laboratory rodents. advances as an understanding of the role of Ronald Herberman (died June 2, 2013, at age blood clots in heart attacks. Early in her career, George F. Borge (died on August 7, 2013, at 72) was a senior investigator and held leader- she was a research chemist in NICHD’s Labora- age 75) was a staff psychiatrist at NIMH, where ship positions in NCI (1966–1985). His lab dis- tory of Biomedical Sciences. he developed his interest in treating alcohol-

14 THE NIH CATALYST JANUARY-FEBRUARY 2014 OBITUARIES

W. Chadwick “Chad” Leyshon (died on May he became the director and senior scientist at Sonia I. Skarlatos (died on August 6, 2013, 20, 2013, at age 87) began his career in 1954 the U.S. Department of Agriculture’s Human at age 59) was deputy director of the NHLBI as a medical technician in the Clinical Center. Nutrition Center (Beltsville, Md.). Division of Cardiovascular Sciences. During her He later worked as a biologist at the National 20-year career with NHLBI, Skarlatos became Peter T. Mora (died January 11, 2013, at age 88) Institute of Dental Research (now NIDCR). a national and international leader in vascular conducted research for about 25 years at NCI science and was one of NIH’s most respected Lewis “Lew” E. Lipkin (died on September and helped develop protease inhibitors to help leaders in advancing an agenda to support 24, 2013, at age 87) was head of the Imaging prolong the lives of AIDS patients. Mora, who translational research. Skarlatos’s husband is Processing Section in the National Institute arrived at NCI in the late 1950s, retired in the Howard Kruth, a senior investigator in NHLBI. of Neurological Disease and Blindness (now mid-1980s as a supervisor in cancer research in NINDS) and later head of NCI’s Imaging Pro- NCI’s macromolecular biology section. John L. Swanson (died on July 8, 2013, at age cessing Section. In the 1970s, he conceived 76) helped revitalize NIAID’s Rocky Moun- Candace B. Pert (died on September 12, 2013, of and initiated the real-time picture proces- tain Laboratories (RML) by championing the at age 67) was a neuroscientist and phar- sor, one of the first special-purpose hardware latest tools and methods in microbiological macologist who, while in graduate school, computers developed for gray-scale image investigation in the 1980s. He came to RML in helped to discover the opiate receptor. She processing and designed to aid in biological 1979 and started internationally recognized held several research positions at NIMH (1975– image analysis. He worked at NIH 1962–1994. research programs on the bacteria that cause 1987), culminating as chief of the Section on gonorrhea, chlamydia, and Lyme disease. He Walter Magruder (died on November 28, Brain Biochemistry. In 1987, she left NIH to was chief of RML’s former Laboratory of Micro- 2013, at age 98) retired from the federal gov- form a biotech company with her husband. bial Structure and Function (1979–1997) and ernment in 1974 after 40 years of service. His Robert Neil Philip (died on January 30, 2013, retired in 2001. career spanned many agencies, including at age 89), a former NIAID epidemiologist, NIH—with the National Microbiological Insti- Rodney Ulane (died on March 7, 2013, at age served for more than 30 years in the Public tute (now NIAID), NCI, and NIAMS. 69) was a NIH microbiologist and director of Health Service, including appointments at scientific programs at the Office of Extramural Robert L. Martensen (died on September 26, NIH in Bethesda (1949–1956) and at NIAID’s Research and spent a total of 24 years at NIH. 2013, at age 66) directed the Office of NIH Rocky Mountain Laboratories (RML) in Ham- He held various positions beginning in 1971 History until his retirement (2007–2012). Pre- ilton, Mont. (1960–1982). Philip was recog- including in what is now NIAMS, NICHD, Center viously, he had been a physician in emergency nized internationally for his contributions to for Scientific Research, and NIGMS. He left rooms and intensive-care units and a profes- the diagnosis and control of Rocky Mountain NIH in 1991, to run M.D.-Ph.D. programs at two sor in bioethics and medical history at Harvard spotted fever. Philip’s father, Cornelius B. medical schools, and returned to NIH in 2009. and Tulane. At NIH, he expanded the Stetten Philip, had also worked at RML (1930–1970). fellow research program, which brings in post- Charles L. Williams, Jr. (died on January 5, Michael Potter (died on June 18, 2013, at age docs in medical history, and built up the office. 2013, at age 96), represented the United States 89), a scientist at NCI whose research led to at international health conferences and was a Nancy K. Mello (died on November 25, 2013, greater understanding of tumors and the director of international research at NIH. After at age 78), who became a leading researcher immune system, won the Lasker award in 1984 26 years in the U.S. Public Health Service, in the field of substance abuse, directed a for his fundamental research into the genetics Williams became deputy director of the Pan research program at NIMH’s National Center of immunoglobulin molecules. He joined NCI American Health Organization, a branch of the for Prevention and Control of Alcoholism. In in 1954 and worked there for more than 50 World Health Organization, in 1967. He was 1974, she and her husband co-founded the years. He was a principal investigator in NCI’s later executive vice president of the American Alcohol and Drug Abuse Research Center at Laboratory of Cell Biology and was chief of the Association for World Health (1979–1980). McLean Hospital (Belmont, Mass.). Laboratory of Genetics (1982–2003).

John Milner (died on December 31, 2013, Milton Puziss (died on October 9, 2013, at age at age 66), well known for his broad under- 93), a microbiologist who helped develop the standing of nutrition and its role in cancer pre- first human vaccine against anthrax in the vention, was chief of the Nutritional Science United States in the late 1950s, joined NIAID READ EXPANDED VERSIONS OF THESE OBITUAR- Research Group in NCI’s Division of Cancer in 1968 and retired as chief of the bacteriology IES AND ADDITIONAL ONES ONLINE AT: http://irp.nih.gov/catalyst/v22i1/obituaries Prevention (2000–2012). After leaving NIH, and virology branch in 1986.

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

Recently Tenured

SUSAN AMARA, NIMH JULIA COOPER, NCI-CCR MARIANA KAPLAN, NIAMS SCOTT YUNG HO KIM, CC SAM MBULAITEYE, NCI-DCEG

SUSAN AMARA, PH.D., NIMH JULIA PROMISEL COOPER, PH.D., NCI-CCR physiology, and acute regulation of neu- Scientific Director of NIMH; Principal Senior Investigator and Head, Telomere rotransmitters. My lab has demonstrated Investigator, Laboratory of Molecular and Biology Section, Laboratory of Biochemis- that transporter proteins can serve dual Cellular Neurobiology, Section on Molecular try and Molecular Biology functions as transporters and as substrate- and Cellular Signaling Education: Emory University, Atlanta (B.S. in Education: Stanford University, Stanford, gated ion channels, revealing additional biology); University of Colorado Health Sci- Calif. (B.S. in biological sciences); University mechanisms by which carriers regulate ences Center, Denver (Ph.D. in biochemistry/ of California, San Diego (Ph.D. in physiology neuronal excitability. Such transporter pro- biophysics/genetics) and pharmacology) teins are targets for addictive drugs and for Training: Postdoctoral training at NIADDK Training: Postdoctoral training at U. of medications that treat mental disorders such (now NIDDK and NIAMS); University of California, San Diego, and Yale (New Haven, as depression and attention deficit hyper- Colorado at Boulder (Howard Hughes Medi- Conn.) activity disorder. These proteins play key cal Institute); and Imperial Cancer Research Before coming to NIH: Professor and chair roles in neuronal communication, memory, Fund (London; now Cancer Research UK) of the Department of Neurobiology and co- and learning. Before coming to NIH: London Research director of the Center for Neuroscience at the As the scientific director for NIMH’s Institute, Cancer Research UK University of Pittsburgh intramural research program, I am pro- Came to NIH: In 1992 for training Came to NIH: In 2013 moting an environment that is conducive Selected professional activities: Organized Selected professional activities: Member, to productive research and the training several international conferences National Academy of Sciences (chair, Sec- of clinical and basic scientists. NIMH Outside interests: Traveling; hiking; eating; tion 23); past president, Society for Neu- researchers study the behavioral, systems, cooking; going to the theater; spending time roscience; Board of Scientific Counselors, cellular, and molecular mechanisms of with her adult children NIAAA Scientific Advisory Board, Gladstone normal brain function as well as conduct clinical investigations into the diagnosis, Institute of Neurological Disease; scientific Research interests: I and my lab focus on treatment, and prevention of mental ill- advisory board, Brain and Behavior Research telomeres, the nucleoprotein complexes ness (including mood disorders and anxiety, Foundation; scientific advisory board, and that form the ends of linear chromosomes. schizophrenia, obsessive-compulsive disor- Gill Center for Biomolecular Medicine Telomeres protect our genomes and cho- der, attention deficit hyperactivity disorder, Outside Interests: Traveling around the world reograph chromosome movements; they and pediatric autoimmune neuropsychiatric with her husband; relaxing with a good cup affect a range of biological processes from disorders). The intramural research program of coffee cancer avoidance to healthy gamete for- has the opportunity to do many innovative mation. They prevent the degradation and things at different levels and that one can’t Research interests: My research examines fusion of chromosome ends and ensure that do elsewhere. The ability to be nimble and the effect of psychostimulant and antide- natural chromosome ends do not elicit the occasionally take risks is a unique aspect of pressant drugs on the signaling properties, cell-cycle arrest pathways that respond to the intramural research program.

16 THE NIH CATALYST JANUARY-FEBRUARY 2014 COLLEAGUES

Selected professional activities: Author of damage-induced DNA breaks. Telomeres Research interests: My research has Evaluation of Capacity to Consent to Treat- are a particular focus of our research on focused on unraveling the fundamen- ment and Research (Oxford, 2010); profes- tumorigenesis (which is associated with tal mechanisms that lead to the devel- sor of psychiatry (adjunct), U. of Michigan genomic instability and telomerase activa- opment and perpetuation of systemic Outside interests: Trout fishing; music; sports tion) and aging (which is accompanied by autoimmune disorders, particularly sys- (remains a loyal Michigan Wolverine) a progressive decline in telomere length). temic lupus erythematosus (SLE) and However, the complete repertoire and rheumatoid arthritis (RA), and their Research interests: Most of my work has underlying mechanisms of telomere func- associated organ damage. I and my lab focused on the ethics of human subject tion are not yet understood. are trying to determine how and why research—the assessment of the decision- The telomeres of fission yeast are premature vascular damage and athero- making capacity of people who are potential remarkably similar to those of humans but sclerosis occur in SLE and RA, with an subjects of clinical research; surrogate con- provide precise genetic manipulability. Con- interest in how innate immune responses sent for dementia research; ethics of sham cepts we have developed by studying fission contribute to endothelial perturbations. neurosurgical trials; and informed consent yeast telomeres have been shown to predict We are characterizing how abnormal and therapeutic misconception—as well as observations in mammals. We are exploring neutrophil responses in autoimmune some work on the reform of institutional the cell-cycle regulation of telomere func- disorders contribute both to the loss of review boards. tion, the fascinating roles taken on by telo- immunological tolerance and to end- Because bioethics is still an evolving meres in controlling spindle formation and organ damage, including the putative field in terms of empirical research, I’m centromere assembly during meiosis, and role of neutrophil extracellular traps very interested in using a variety of meth- surprising ways in which some cells (such as (networks of extracellular fibers, pri- ods to integrate theoretical and empirical telomerase-minus cancer cells) can survive marily composed of DNA from neutro- approaches. For example, we’ve used a in the absence of canonical telomeres. phils, which bind pathogens). I am also method called democratic deliberation in interested in doing preclinical and clini- which our subjects spend a day learning cal studies and trials to identify novel and deliberating about a complex bioethi- MARIANA KAPLAN, M.D., NIAMS biomarkers and therapeutic targets that cal issue. We can then obtain from them Senior Investigator; Chief of the Systemic may prevent premature vascular damage more considered ethical views than just Autoimmunity Branch and chronic inflammation in systemic their impressionistic opinions. We’ve also Education: National Autonomous University autoimmunity. of Mexico, Mexico City (M.D.) used mixed methods (in-depth qualita- Training: Internal medicine residency at the tive interviews along with experimental National Institute of Medical Sciences and SCOTT YUNG HO KIM, M.D., PH.D, CC surveys that use a philosophical linguistics framework) to examine whether research Nutrition (Mexico City); rheumatology fellow- Senior Investigator, Department of Bioethics ship/postdoctoral training at University of Education: Wheaton College, Wheaton, Ill. subjects conflate research participation Michigan (Ann Arbor, Mich.) (B.A. in philosophy); University of Chicago, with treatment—a phenomenon called Before coming to NIH: Professor of medicine, Chicago (Ph.D. in philosophy); Harvard “therapeutic misconception” that is Division of Rheumatology, U. of Michigan Medical School, Boston (M.D.) thought to be highly prevalent but which Came to NIH: In 2013 Training: Residency in psychiatry, Mas- we are finding may be due to a measure- Selected professional activities: Member, sachusetts General Hospital (Boston); ment problem. And I’ve begun some new American Society of Clinical Investigation; National Research Service Award in Geriat- collaborative projects in the Department Lupus Foundation of America Scientific Advi- ric and Neuropsychiatric Psychopathology of Bioethics, which I’m finding to be a sory Council; adjunct professor, University of Research, University of Rochester (Roches- wonderfully collegial place. Michigan; Section Editor, Journal of Immunol- ter, N.Y.) ogy (2009–2013) Before coming to NIH: Co-director, Center If you have been recently tenured, the NIH Outside interests: Spending time with her for Bioethics and Social Sciences in Medicine, Catalyst will be contacting you soon about family; traveling; playing piano; reading University of Michigan (Ann Arbor) including you on these pages. literature; listening to music Came to NIH: In 2013

CONTINUED ON PAGE 18

http://irp.nih.gov/catalyst 17 : COLLEAGUES ANNOUNCEMENTS

Recently Tenured CONTINUED FROM PAGE 17 DEMYSTIFYING MEDICINE Tuesdays, starting January 7, 2014 4:00–6:00 p.m. SAM MBULAITEYE, M.D., NCI-DCEG the association between malaria-resistance Building 50, Conference Room Senior Investigator, Infections and Immu- gene polymorphisms, malaria parasite diver- The “DeMystifying Medicine” course, in its noepidemiology Branch, NCI Division of sity, and EBV genetic variants with BL. 13th year, bridges the gap between advances Cancer Epidemiology and Genetics (DCEG) in biology and their application to human dis- Education: Makerere University, Kampala, Additionally, in collaboration with the NCI ease. Each class features presentations by a Uganda (MBChB and M.Med. in internal medi- Office of Cancer Genomics, I am using clinician, a researcher, and often a patient. cine); University of Cambridge, Cambridge, fresh-frozen tumor tissues collected from For more information visit http://demystify- U.K. (M.Phil. in epidemiology and biostatistics) a subset of BL cases to conduct BL tumor ingmedicine.od.nih.gov or contact Win Arias Before coming to NIH: Senior medical officer, genome sequencing. My studies may lead at [email protected]. Uganda Virus Research Institute (Entebbe) to the discovery of molecular abnormalities January 7: “Worldwide Emergence of Drug- Came to NIH: In 2000 as a research fellow; that drive BL and that may be targeted for resistant Infections and What’s Being Done became tenure-track investigator in 2005 therapy or prevention. about It”; Anthony Fauci (NIAID), Jeffrey Selected professional activities: Adjunct My work on BL outside of Africa seeks Taubenberger (NIAID) lecturer at George Washington University to measure the risk of BL in immunosup- January 14: “Itching (Pruritus): Mechanisms, School of Public Health (Washington, D.C.); pressed populations, such as those who are Diseases, and Treatment”; Mark Hoon editorial board member, International Journal HIV-positive or receive immunosuppression (NIDCR); Irwin Arias (NICHD/CC) of Cancer and Frontiers in Cancer Epidemiol- medications to prevent rejection of trans- January 21: “Cancer Screening: Science vs. ogy and Prevention; co-editor-in-chief, Infec- planted organs. I am conducting studies to Intuition (Example Prostate Cancer)”; Barnett tious Agents and Cancer investigate whether BL in settings where Kramer (NCI), Peter Pinto (NCI) Outside interests: Biking; hiking; jogging; malaria is absent differs from BL in Africa. January 28: “Adaptor Diseases: Bridging running marathons; stargazing Cell Biology and Medicine”; Juan Bonifacino PECASE WINNERS (NICHD), Craig Blackstone (NINDS) Research interests: Burkitt lymphoma February 4: “Obesity: Etiology, Pathogen- The Presidential Early Career Awards for (BL) is the most common childhood esis, and Why Weight Loss Is Difficult”; Jack Scientists and Engineers (PECASE) are cancer in Africa and the third most Yanovski (NICHD), Kevin Hall (NIDDK) the highest honor bestowed by the U.S. common lymphoid malignancy in devel- February 11: “HIV: Changing Paradigms and government on outstanding scientists and oped countries. My work seeks to measure the Washington-Baltimore Scene”; John engineers beginning their independent the association between malaria markers Coffin (NCI), Henry Masur (CC) careers. NIH intramural scientists have (parasite prevalence, load, and genotypes) February 18: “Pertussis (Whooping Cough): A been on the list of PECASE recipients and the immune response to malaria Lesson in Vaccines”; John Robbins (NICHD), every year since 1997. Congratulations proteins in patients at risk for BL. I am Alexandra Freeman (NIAID) to the 2012 winners: Jessica Gill (NINR), interested in understanding how this rela- February 25: “Chromosomal Transloca- who is seeking effective ways to identify tionship is modified by other infections— tion: Cellular Mechanism and Clinical Con- trauma patients who are at high risk for such as Epstein–Barr virus (EBV), human sequence”; Tom Misteli (NCI), John Barrett psychological and neurological deficits immunodeficiency virus (HIV), and stool (NHLBI) and inform the interventions that will parasites—that are common in children March 4: “The Intestinal Microbiome: Role in support their recovery; Susan Harbison with BL. I am the principal investigator Nutrition, Metabolism, and Inflammation”; (NHLBI), who is investigating the genetic in the Epidemiology of Burkitt Lymphoma Yasmine Belkaid (NIAID), Warren Strober networks underlying sleep and their inter- in the East African Children and Minors (NIAID) actions with the environment; and Todd (EMBLEM) study, a multiyear, multisite March 11: “Water, Water Everywhere and Not Macfarlan (NICHD), who is exploring fun- study of childhood BL (http://dceg.cancer. a Drop to Drink”; Karen Frank (CC), Gordon damental mechanisms of gene regulation gov/research/cancer-types/lymphoma- Hager (NCI) and epigenetic inheritance during embryo burkitt-hodgkin-non-hodgkin/burkitt- March 18: “Drug-Induced Liver Injury: Who, development. lymphoma-emblem). Using questionnaire What, When, and How”; Leonard Seefe, (for- data and genomic methods, I will evaluate merly NIH/FDA), Chris Austin (NCATS)

18 THE NIH CATALYST JANUARY-FEBRUARY 2014 : ANNOUNCEMENTS

March 25: “Human Papillomavirus: Preventing independent scientists, research fellows, staff NINDS, NHLBI, NCI, Johns Hopkins, and the Cancer”; Douglas Lowy (NCI), Carter Van- fellows, and postdoctoral fellows who have at University of Maryland School of Medicine. Waes (NIDCD) least one year of postdoctoral research expe- The WALS speaker, Doug Wallace (Perel- April 1: “Sleep: Perchance to Dream”; Carolyn rience. Projects are generally limited to one man School of Medicine, University of Penn- Beebe Smith (NIMH), Susan Harbison (NHLBI) year of funding and cannot exceed $100,000. sylvania), will give a presentation entitled April 8: “Drug Resistance in Cancer: Mecha- For more information, contact Cindy Davis at “A Mitochondrial Etiology of Metabolic and nisms and Management”; Michael Gottesman [email protected]. Degenerative Diseases, Cancer and Aging.” (NCI), Antonio Tito Fojo (NCI) Registration is not required unless you wish to April 15: “HAV and HCV RNA Viruses: Clinical POSTDOCTORAL RESEARCH ASSOCIATE submit a poster abstract. Two poster abstracts and Basic Advances and Challenges”; Marc (PRAT) PROGRAM will be chosen by intramural NIH scientists for Ghany (NIDDK), Nihal Altan-Bonner (NHLBI) Application deadline: March 7, 2014 platform presentations. The WALS portion April 22: “Transplanting Hearts and Other The PRAT program, sponsored by NIGMS, is will be videocast and archived at http://vid- Organs”; Jonah Odim (NIAID), Allison Sklarew now accepting applications for the fall 2014 eocast.nih.gov. To submit poster abstracts (Washington Regional Transplant Community) class. PRAT is a competitive fellowship pro- or for information about the speakers, go April 29: “Malaria: Origin and Advances in gram providing up to three years of support to https://2014migsymposium.eventbrite. the World’s Major Killer”; Beatrice Hahn (Uni- for fellows conducting research within the com. To request reasonable accommodation, versity of Pennsylvania), Carolina V. Barillas- NIH or FDA Intramural Research Programs. contact Steve Zullo at [email protected] Mury (NIAID) Fellows participate in an ongoing scientific or 240-271-7097 or call the Federal Relay, May 6: Finale (to be announced) seminar series tailored to the PRAT program, 800-877-8339. as well as receive additional training in a vari- “PLASTICITY BEYOND THE SYNAPSE— ety of career skills and mentoring. Research NIH MANAGEMENT INTERN PROGRAM REGULATION OF MYELINATION BY ACTION proposed by PRAT fellows encompasses a Unlock a New Career Path POTENTIALS” wide variety of emerging areas of science, Recruiting: April 7–11, 2014 Neuron-Glia Interactions (SIG) Lecture but a particular emphasis is placed on proj- The NIH Training Center is pleased to Tuesday, February 4, 2014 ects incorporating aspects of quantitative and announce the new recruitment season for 2:00–3:00 p.m. systems pharmacology or computational biol- Management Interns (MIs). The MI program is Building 40, Room 1201/1203 ogy. Additional information about eligibility, a highly competitive, two-year career-devel- Douglas Fields (NICHD senior investigator definition of research areas of emphasis, and opment program for current NIH employees. and section chief; editor-in-chief of Neuron the application process can be found at http:// MIs come from a variety of job backgrounds Glia Biology) will be making a presentation www.nigms.nih.gov/Training/pages/PRAT. including scientific and administrative fields. at the Neuron-Glia Interactions SIG meet- aspx or contact the PRAT program director at On completion of the program, MIs transition ing. All meetings and the SIG are open to all [email protected] or 301-594-3827. into an administrative or management career members of the NIH community and extramu- in one of many areas throughout NIH. Eligible ral researchers in the Baltimore-Washington TRANSFORMATIONAL MEDICINE IN THE employees are invited to apply. For program metro area. For more information contact Amy MITOCHONDRIAL AGE FAQs, upcoming information sessions, and Shafqat at [email protected]. To join the Wednesday, April 2, 2014 details about eligibility, visit http://training- LISTSERV, send your request to neuron-glia@ 8:00 a.m.–4:00 p.m. center.nih.gov/intern/mi/. list.nih.gov. (See page 7 for more on this SIG.) (WALS 3:00–4:00 p.m.) Poster Abstracts due February 28, 2014 NLM SPECIAL EXHIBIT: FROM DNA TO BEER THE OFFICE OF DIETARY SUPPLEMENTS Event URL: https://2014migsymposium. http://www.nlm.nih.gov/exhibition/ (ODS) RESEARCH SCHOLARS PROGRAM eventbrite.com fromdnatobeer Letters of Intent due May 2 All are welcome to attend this day-long On display through April 18, 2014 The ODS Research Scholars Program is a one- symposium, which includes the Wednesday History of Med. Reading Room, NLM (Bldg. 38) year competitive scholarship opportunity to Afternoon Lecture in the late afternoon. The “From DNA to Beer: Harnessing Nature in study the role of dietary supplements in health morning session on “Mitochondria and the Medicine and Industry” explores some of the promotion and disease prevention. This pro- Brain” and the afternoon session on “Mito- processes, problems, and potential inherent gram is targeted to early-career scientists, chondria, Cancer, and Innovative Technol- in technologies that use microorganisms for including tenure-track investigators, early ogy” will feature scientists from NIA, NICHD, health and commercial purposes.

http://irp.nih.gov/catalyst 19

DALE LEWIS, NCI

DHHS/NIH Permit No. G-802 Permit No. FIRST-CLASS MAIL FIRST-CLASS POSTAGE & FEES PAID & POSTAGE Publication No. 14-6250 Publication are safely handling handling safely are MICHAEL ESPEY, NIDDK ESPEY, MICHAEL NCI KOHN, C. ELISE CC LEITMAN, SUSAN NICHD LOUIS, BUCK GERMAINE NIEHSMILLER, DAVID NIAIDMOSS, BERNARD NCI PARK, HYUN NIAMS PLOTZ, PAUL NHGRI SEGRE, JULIE NIASINGLETON, ANDY NICHD STORZ, GISELA SUMMERS,CC RONALD OIR WYATT, RICHARD EDITORIAL ADVISORY BOARD ADVISORY EDITORIAL APPELLA,NIDDK DAN NIDDK DAVIES, DAVID Zhong Qian Zhong

(left) and and (left) DARRYL LEJA DARRYL Sangmi Lee Sangmi REBECCA BAKER, ERIC BOCK, REBECCA BURGESS LESLEY EARL, STEVEN HOLLAND ADAM KUSZAK, MEGHAN MOTT SUMAN MUKHERJEE CHRIS PALMER, JOSEPH TIANO PHOTOGRAPHERS/ILLUSTRATORS BRANSON ERNIE BRANSON, BILL FOLKERS RICH CARR, JANICE KLUMPP, CARLEEN JUDITH LEWIS, STOFFER DALE EDITORIAL INTERN EDITORIAL JENNIFERSARGENT WRITERS CONTRIBUTING

(NCI) won first place in the third annual “In-Focus Safe Workplaces for All” photography All” for Workplaces annual “In-Focus third Safe the in first place won (NCI)

challenged anyone with a passion for photography to use their imagination and creativity to capture to creativity and imagination their use to photography for passion a with anyone challenged community. NIH the with it share and health and safety workplace of image an Dale LewisDale postdocs how shows that image this for contest face shields, radioactive the lab. in wearing protective are Both materials whileclothing, and gloves than more for NIH at been has who Lewis, containers. approved in materials the of disposing are they this in place second won also remember, can he as long as beentakingpictures has for and years 19 year’s contest for a photo of window washers in action. Sponsored by the Division of Occupational contest of All” Research Services, Workplaces for Office the “In-Focusthe Safetyin Safe and Health Doing It Right It Doing

PHOTOGRAPHIC MOMENT PHOTOGRAPHIC WRITER-EDITOR WANJEK CHRISTOPHER OIR Communications, of Director EDITOR COPY ROBERTS SHAUNA PUBLISHER OD GOTTESMAN Research, MICHAEL Intramural for Director Deputy EDITORS GALLIN I. JOHN Center Clinical NIH Director, METZGER HENRY Emeritus Scientist EDITOR MANAGING CARTER STEPHENSONLAURA

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is published online: pages. pages. The NIH Catalyst and can be recycled office white paper. as Printed on at least 20% recycled on paper content Printed Catalyst Building 1, Room 333 Building 1, Room 0183 MSC 20892 Maryland Bethesda, U.S. DEPARTMENT OF HEALTH AND AND OF HEALTH DEPARTMENT U.S. SERVICES HUMAN of Health Institutes National your reactions to anythingto your reactions on the Also, we welcome “letters and publication for editor” the nih.gov; fax: 301-402-4303; or mail: 333. Room 1, Building the space to the right, why not not why right, the to space the send it via e-mail: catalyst@ a quotation or confession that that confession or quotation a and appreciate might scientists that would be fit to print in other graphic that reflectsan aspect of life(including laboratory life) or at NIH If you have a photo or e-mail: [email protected] The NIH Catalyst http://irp.nih.gov/catalyst Building Room 1, 333, NIH Bethesda, MD 20892 Ph: 301-402-1449 Fax: 301-402-4303 bimonthly for and by the intramural scientists at NIH. Address correspondence to: The NIH Catalyst CATALYTIC REACTIONS? CATALYTIC Official Business Use $300 Private for Penalty