NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 28 ISSUE 6 • NOVEMBER–DECEMBER 2020

Resistance to the NHGRI Scientists Study Ancient Dog Breed Plague May Be a New Guinea Singing Dogs May Hold Clues to Human Vocalization Double-Edged Sword BY NATALIE HAGEN, NCATS BY ETHAN SMITH, NINR

Evolutionary pressure to survive CREDIT: JAMES K. MCINTYRE, NEW GUINEA HIGHLAND WILD DOG FOUNDATION DOG WILD HIGHLAND GUINEA NEW MCINTYRE, K. JAMES CREDIT: the bubonic plague may have selected for genetic mutations that protect certain Mediterranean populations from being infected by the infamous Yersinia pestis, the bacterium behind the plague. But evolution isn’t perfect. Being able to survive the plague may also be the reason for today’s prevalence of another ancient disease—familial Mediterranean fever (FMF)—National Human Genome Research Institute (NHGRI) researchers recently reported in Nature Immunology (Nat Immunol 21:857–886, 2020). FMF, an autoinflammatory disease that mainly affects people of Mediterranean and Middle Eastern descent, is caused by mutations in the MEFV gene. The gene encodes pyrin, a protein involved in the Studying the New Guinea highland wild dog, the original New Guinea singing dog, may help scientists understand how inflammatory response. In healthy people, human vocalization developed. Shown: a male New Guinea highland wild dog. pyrin helps immune cells fight infection by increasing inflammation and producing The New Guinea singing dog, whose harmonious wolf-like howls inflammation-related molecules. In FMF sound eerily like whale songs, was thought to have been extinct in the wild for some 50 patients, though, pyrin is activated without years. But researchers at the National Human Genome Research Institute (NHGRI) being triggered by an infection and can cause reported, in the Proceedings of the National Academy of Sciences, that their genome analysis episodes of hyperinflammation: fever, chest has confirmed that this breed still roams the New Guinea Highlands. Moreover, pain, arthritis, and abdominal pain so bad it CONTINUED ON PAGE 14 can be mistaken for appendicitis. Without CONTENTS treatment, FMF can lead to renal failure and FEATURES • |1| Resistance to the Plague May Be a Double-Edged Sword |1| Ancient dog breed death. People with two copies of the mutated may hold clues to human vocalization |5| NIH’s Outstanding Women Fellows |9| COVID-19 MEFV gene are predisposed to FMF; those Timeline (September–October) |15| WALS Lecture: Joan Steitz on viral noncoding RNA with only one copy of the mutated gene may DEPARTMENTS • |2| DDIR: Nobel Prize to Harvey Alter |3| Abbreviations |4| Training: Taking develop FMF, but at a lower frequency. Control of the Job Search |6, 16| News You Can Use: National Death Index; Cyber Health But it turns out that having one or two |7| Tech Transfer: Mobile-Health Platform |8| Research Briefs |10| Alumni: Andrea Pfeifer

CONTINUED ON PAGE 12 |13| History: Patches and Coloring Books |17| SIG Beat: Sexual and Gender Minority Health |18| Colleagues: Recently Tenured |24| Photographic Moment: Award–Winning Fish FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

A Wonderful October Surprise for the NIH Harvey Alter Wins the Nobel Prize BY MICHAEL GOTTESMAN, DDIR

Unless you have been on Mars, a high percentage of chronically infected hematologist, Harvey began to work in which incidentally is closer to Earth than individuals. So treatment of all infected the NIH Clinical Center Blood Bank and it will be for next 15 years and is easily patients has become a goal of public-health became interested in detecting antigens visible as an orange orb in the southeast experts. Harvey continues to study the in blood (using a standard technique) that sky after sunset, you know that early natural history and outcomes of hepatitis might contribute to transfusion reactions. Monday morning, on October 5, 2020, C infection and is collaborating with Marc This work was stimulated by a long-term our own Harvey Alter, senior scientist Ghany and others in the Liver Diseases collaboration with Baruch Blumberg. in the NIH Clinical Center, got a call Branch (in the National Institute of Diabetes Harvey and Baruch discovered the Australia from Sweden notifying him that he and Digestive and Kidney Diseases) to Antigen, which turned out to be the hepatitis was sharing this year’s Nobel Prize in conduct long-term follow-up studies of B antigen. Baruch Blumberg received the Medicine or Physiology for his pioneering patients to see if cirrhosis is prevented or Nobel Prize for this work. work on defining and detecting the goes away after treatment. • Offers researchers the ability to do hepatitis C virus. Although this work had There is probably no one at NIH long-term studies that are hypothesis- previously been recognized by the Lasker whose work has had more impact on generating: Harvey has commented about Prize in 2000 and the Canada Gairdner improving the public health, and so it seems how the NIH IRP enabled him to collect International Award in 2013, the NIH appropriate to ask how this work came to and store longitudinal samples from cardiac- had pretty much given up hope that the be in the intramural research program surgery patients, who had about a 30% Nobel Prize committee would recognize (IRP). How did Harvey himself come to incidence of hepatitis related to the clinically Harvey’s critical contribution to what has be in the IRP? Like many “Yellow Berets” required transfusions, and pursue his since become the potential eradication (including myself), he was invited by the research interests over many years without (through drug treatment) of this virus in federal government in the 1960s to report having to write grants. It soon became clear infected individuals, and the elimination for military duty. We sought instead to that only 25% of post-transfusion hepatitis of a public-health plague. provide service to our country by working was due to hepatitis B and none due to To be clear, Harvey’s work had made it at NIH; Harvey chose to work at the NIH hepatitis A virus. Hence, the vast majority of possible to cleanse the blood supply of the Clinical Center. (The term “Yellow Beret” cases were due to a new infectious entity that agents that caused hepatitis (both B and C) came about because those who came to NIH the research team cautiously called non-A, through blood transfusions. His work was to fulfill the selective service obligation for non-B hepatitis. instrumental in leading to the development every male physician—or, as some said, to Harvey, Bob Purcell, Steve Feinstone, of new diagnostic and therapeutic agents and avoid the draft—were initially perceived and Patrizia Farci set out to discover the providing the scientific basis for instituting as cowards, the opposite of the brave U.S. missing agent. Harvey says he doubts that blood-donor screening programs that have Army Special Forces called the Green these studies could have been done anywhere decreased the incidence of transfusion- Berets. Later, however, most considered other than NIH. Only the intramural transmitted hepatitis to near zero. “Yellow Beret” to be a badge of pride.) program would have supported his large But hepatitis C could still be transmitted Harvey’s choice precipitated a series of blood repository and his chimpanzee in other ways such as shared needles events that clarify why the IRP continues to studies, both of which proved critical to among intravenous-drug users. One be the source of innovative and high-impact the discovery of hepatitis C, or funded the continuing consequence of hepatitis C scientific discoveries. Consider how the IRP: “nondirected” research when it wasn’t clear infection is cirrhosis of the liver and the • Provides opportunities to collaborate where the research was going. The actual eventual development of liver cancer in with world-class scientists: Trained as a cloning of the hepatitis C viral genome was

2 THE NIH CATALYST NOVEMBER–DECEMBER 2020 NIH ABBREVIATIONS FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH CBER: Center for Biologics Evaluation and Research, FDA CC: NIH Clinical Center CCR: Center for Cancer Research, NCI CIT: Center for Information Technology DCEG: Division of Cancer Epidemiology and Genetics, NCI DIPHR: Division of Intramural Population Health Research, NICHD FAES: Foundation for Advanced Education in the Sciences FARE: Fellows Award for Research Excellence FelCom: Fellows Committee FDA: Food and Drug Administration FNIH: Foundation for the NIH Frederick National Laboratory accomplished by a group led by Michael • Allows researchers to take advantage of FNL: IRP: Intramural Research Program Houghton at Chiron (with whom this special resources: The NIH Clinical Center HHS: U.S. Department of Health year’s Nobel Prize was shared along with is a unique resource. Harvey’s career at NIH and Human Services NCATS: National Center for Advancing NIH-supported researcher Charles Rice at reflects the optimal use of this resource, Translational Sciences Rockefeller University in New York). But which provides access to an unusual patient NCBI: National Center for Biotechnology Harvey’s pioneering work defining the population; supports the ability to do studies Information NCCIH: National Center for Complementary existence of this virus and his establishment over several decades; and has the capacity and Integrative Health of a repository of coded blood samples that to collect and characterize clinical samples NCI: National Cancer Institute included non-A, non-B hepatis proved and data from patients. NEI: National Eye Institute NHGRI: National Human Genome critical for the discovery. • Dedicates itself to the public health: At Research Institute • Recognizes unusual talent: No one is its core, Harvey’s work is about defining an NHLBI: National Heart, Lung, and Blood Institute more self-effacing, more generous, and more important public-health problem (hepatitis- NIA: National Institute on Aging able to see the humor in most situations than virus-contaminated blood), doing research NIAAA: National Institute on Alcohol Harvey. But his pleasant exterior masks a to understand the nature of the problem, Abuse and Alcoholism NIAID: National Institute of Allergy very sharp, persistent, and intuitive intellect and applying knowledge to alleviate the and Infectious Diseases that is apparent to all of us who have gotten public-health consequences. This dedication NIAMS: National Institute of Arthritis and Musculoskeletal and Skin Diseases to know Harvey well. He is a very serious is written into the mission statement for the NIBIB: National Institute of Biomedical and effective scientist who just happens to NIH and its Clinical Center and underlies Imaging and Bioengineering be able to laugh at himself and his life’s work much of the work done at the NIH. NICHD: Eunice Kennedy Shriver National Institute of Child Health and and along the way earn the support of his Human Development colleagues and supervisors. I like to think So please join me in congratulating NIDA: National Institute on Drug Abuse NIDCD: National Institute on Deafness that NIH has a good eye for talent. Harvey’s Harvey Alter and the NIH for this and Other Communication Disorders career here illustrates that quality. wonderful recognition of a life’s work NIDCR: National Institute of Dental dedicated to the public health, and let and Craniofacial Research NIDDK: National Institute of Diabetes us redouble our efforts to preserve the and Digestive and Kidney Diseases environment here that enabled our latest NIEHS: National Institute of Environmental Health Sciences Nobel laureate’s lifesaving work. NIGMS: National Institute of General Medical Sciences NIMH: National Institute of Mental Health NIMHD: National Institute on Minority There are now six Nobel laureates who did the Health and Health Disparities entirety of their award-winning research at the NINDS: National Institute of NIH as federal scientists: Marshall Niren- Neurological Disorders and Stroke NINR: National Institute of Nursing Research berg, Julius Axelrod, Christian Anfinsen, NLM: National Library of Medicine D. Carleton Gajdusek, Martin Rodbell, OD: Office of the Director and Harvey Alter. For a complete list of NIH OITE: Office of Intramural Training and Education Nobel laureates including those who trained or OIR: Office of Intramural Research CREDIT: ERNIE BRANSON ERNIE CREDIT: worked extensively in one of NIH’s intramural ORS: Office of Research Services Harvey Alter shared the 2020 Nobel Prize in Medicine or laboratories, visit https://irp.nih.gov/about-us/ ORWH: Office of Research on Women’s Health Physiology for the “discovery of Hepatitis C virus.” Office of Technology Transfer honors/nobel-prize. OTT:

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

From the Fellows Committee Taking Control of the Job Search During the Pandemic BY CRAIG MYRUM, NIA

Even in normal times, applying for a selective liberal arts college, my job informational interviews. I even wrote academic faculty positions is time- packet would need a solid “Teaching” an article about it for the May–June 2020 consuming, and the competition is fierce. statement. I dusted off a draft that I had issue of the NIH Catalyst (https://irp.nih. Throw in a pandemic, your chances of written in NIH’s “Scientists Teaching gov/catalyst/v28i3/the-training-page). snagging that long-sought-after position Science” (https://www.training.nih.gov/ But if I thought that getting a job in academia may feel hopeless. Currently sts_main_page) course five years ago. in academia was hard, getting an MSL in the midst of my own job search, I (As a side note, I highly recommended position is almost certainly tougher. have experienced difficult moments, but this course!) Now with four years of Nevertheless, if spring rolls around and I have also fortunately found ways to adjunct teaching (at a couple of local I am still without an academic job, I will alleviate the anxiety. universities) under my belt, I reflected muster up all of the optimism I have left Structured around the academic on my experiences and identified what and again make a plan to control what calendar, academic job postings I personally believe about teaching and I can control. typically peak between September learning and got those thoughts down on That resilience would not be possible and November. So, in March, when I paper. And as required of all academic without a little self-care. For myself, heard about colleges and universities positions, I would also need a solid that means going on runs, exploring beginning to implement hiring freezes publication record. In the absence of new new places in the region (since traveling and rescinding new faculty offers, I was data being generated in the lab during via plane does not sound reasonable worried about my rapidly approaching the COVID-19 lockdown, I wrote a solid at the moment), and maintaining faculty search in the fall. And on top of draft of a review that I had thought about relationships—even if that sometimes that, nonessential laboratory research had for a long while. I drafted cover letters, I requires staying six feet apart. Both come to a standstill as NIH shut down updated my CV, and with the backdrop physical and mental wellness are all but mission-critical functions. My of persistent racial injustice in the news, I imperative during this period of ups plans of submitting one last paper before drafted the all-important “Diversity and and downs. If that’s something that you the job search quickly became unrealistic. Inclusion” statement. I identified what need to work on, the OITE fortunately When in-person professional I could control, and I did what I could has a whole host of resources to get trainings swiftly switched to virtual to control it. you started. Remember—you are also Zoom and WebEx sessions, I attended While I would generally consider in control of your own thoughts and a handful of workshops arranged by myself an optimist, I am also a realist. I behaviors. the Office of Intramural Training and guess that makes me a realistic optimist. If you’re also on the job hunt, I wish Education (OITE). As an introduction So with the already-tough job market in you the very best! to many of these sessions, the OITE academia compounded by the economic staff reminded attendees that many crisis resulting from the COVID-19 Craig Myrum has been a postdoctoral things about the pandemic were out of outbreak, I decided that I needed to fellow at the National Institute on Aging’s our control, but more importantly, that consider a Plan B. A backup. Reminded Laboratory of Behavioral Neuroscience since there were still a great number of things of a Career Spotlight Series session at my 2015. He works in the Neurocognitive that we could control. We could prepare institute a couple of years back, I decided Aging Section, where he studies the our job packets. We could attend to our to look into what it would take to become intersection of memory, aging, and sleep. career development. We could attend to a Medical Science Liaison (MSL). I read When his training is complete in 2021, he our science. And we could control our about the roles and responsibilities of an hopes he will have landed a job at a liberal own thoughts and behaviors. With that MSL, learned more about how clinical arts college where he can both teach and thought in mind, I got to work. trials work through the NIH Office of continue his research. He has been overseeing Since my career aspiration has long Clinical Research (which I reasoned was and contributing to this page since 2016. been to become a faculty member at important to know regardless), and did

4 THE NIH CATALYST NOVEMBER–DECEMBER 2020 FEATURE

Highlighting NIH’s Outstanding Women Fellows 10th Annual Women Scientists Advisors Scholars Symposium BY FRANCES FERNANDO, NICHD

Ever since 2011, the outstanding drug availability, and relapse may involve research achievements of NIH women conflict (arguments with other people). postdocs have been recognized at the Fredriksson’s solution was to use an Annual Women Scientists Advisors electric barrier model to imitate voluntary (WSA) Scholars Symposium. On abstinence, which involves introducing October 5, 2020, postdoctoral fellows Alix adverse consequences (such as punishment) Warburton and Ida Fredriksson presented of continued drug self-administration. their work. They had been selected as The most unexpected finding was that the

WSA scholars from among the 95 women ALIX WARBURTONTA, IDA FREDRIKSSONCI- electric-barrier-induced abstinence increased, recipients of the 2020 Fellows Award for NCI-CCR CCR rather than decreased, oxycodone craving and Research Excellence (FARE). locus is fundamentally unique, which has seeking behavior, suggesting that abstinence different implications for cancer progression, induced by negative consequences (discipline, ALIX WARBURTON (NATIONAL INSTITUTE and the translational potential of applying punishment, incarceration) in humans might OF ALLERGY AND INFECTIOUS DISEASES) basic mechanistic understandings to other paradoxically increase relapse vulnerability Education: Ph.D. in molecular and clinical human viruses.” She mentioned a need for (Neuropsychopharmacology 44:465–477, 2019). pharmacology from the University of further study of the effects of silencing tumor Current projects include using whole- Liverpool (Liverpool, England) suppressors or amplifying oncogenes. brain imaging in rats to identify neural Mentor: Alison McBride, Chief of NIAID’s DNA projections that are activated during relapse; Tumor Virus Section IDA FREDRIKSSON (NATIONAL INSTITUTE and functional magnetic-resonance imaging Talk: “Mechanisms of Tandem Repeat ON DRUG ABUSE) to monitor neural-circuit mechanisms. Formation at HPV Integration Sites in Cervical Education: Pharm.D. from Uppsala University Carcinoma Cells” (Uppsala, Sweden); Ph.D. in neuroscience The NIH WSA Scholars Symposium was Interested in how human from the Karolinska Institute (Solna, Sweden) sponsored by WSA and the NIH Office of papillomavirus (HPV) genomes are Mentor: Yavin Shaham, Chief of NIDA’s Research on Women’s Health. The WSA integrated into cellular chromatin in Behavioral Neuroscience Research Branch committee aims to advance the scientific HPV-associated cancers, Warburton and of the Neurobiology of Relapse Section careers and scientific contributions of women investigates the role and mechanism of Talk: “Incubation of Oxycodone Craving After at NIH. Each year, the WSA selects two or the HPV integration locus in oncogenic Conflict-induced Voluntary Abstinence” three awardees from the pool of female FARE progression. She studies the clonal To better understand the winners for this special recognition and gives selection of integration events that clinical problem of high relapse rates them the opportunity to present their research sustain oncogene expression and the during abstinence from addictive drugs, to the NIH community. To learn more about role of hijacking cellular enhancers Fredriksson decided to study rats to the history and activities of the WSA, visit at HPV-integration loci in cervical determine the mechanisms of incubation https://sigs.nih.gov/wsa. cancer, with emphasis on alterations in (the time-dependent increases in drug- common fragile sites in the gemome. In seeking behavior) of oxycodone craving Frances Fernando is a postbaccalaureate cervical cells, she showed that integrated during abstinence. After a period of drug fellow in the National Institute of Child HPV16 could result in the formation of self-administration, rats experienced an Health and Human Development. After a super-enhancer-like element that drives increase in their drug-seeking behavior completing her training in 2021, she plans transcription of the viral oncogenes (PLoS during a forced drug abstinence period in to pursue a doctorate in public health to Genet 14:e1007179, 2018). the home cage (the classical incubation of work on integrative global health issues When asked about unexpected findings drug-craving model). However, this model and human rights. in her research, Warburton commented on does not mimic the human condition in how “interesting it is that each integration which abstinence is self-imposed despite

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

Access to the National Death Index Made Easy Centralized Database Now Available to NIH-supported Researchers BY SUNITA CHOPRA, NCI

For many long-term clinical the appropriate state offices to obtain copies studies, it is critical for investigators to of death certificates or specific statistical know whether patients have died, and if information such as cause of death. Or to so, when, where, and how. Unfortunately, make things even easier, the “NDI Plus” this information—especially if the patients service can provide cause-of-death codes. died outside the research hospital— Records go back to 1979, and new death has often been difficult and expensive records are added to the NDI file annually. to obtain. Recently, NIH has made it Under the new NIH-NDI agreement, it easier—and free—for NIH-supported will be also easier for investigators to share epidemiologists and other health and Translational Research Informatics System the NDI-linked data with their NIH-funded medical researchers to access a centralized (BTRIS), which is fed data from the Clinical collaborators as well as with those who are database of death-record information held Center’s electronic medical record called not funded by NIH, according to OBSSR by state vital statistics offices. the Clinical Research Informatics System Director William T. Riley. It can be incredibly hard to study the (CRIS). But both BTRIS and CRIS are To submit an NDI application, PIs go natural history of a disease without patient of limited use because their records do not to the NDI Portal (https://www.cdc.gov/ data that show whether people have died show the cause of death for patients who nchs/ndi/portal.htm) and follow the step- and the causes of death, said John Gallin, died outside the Clinical Center, explained by-step instructions. The website includes chief scientific officer of the NIH Clinical Jon McKeeby, chief information officer and information on eligibility requirements, rules Center and NIH associate director for chief of the Department of Clinical Research for obtaining NDI information, criteria for clinical research. He’s been studying a Informatics at the NIH Clinical Center. approval, and more. The NDI data can only genetic immunodeficiency disorder called The NDI, however, does show the cause be used for statistical purposes in public chronic granulomatous disease for almost of death no matter where the patient died. health and medical research. Once PIs are 40 years. Although he and other NIH- So NIH decided to explore ways to help sure their projects meet the criteria, they fill supported researchers (both intramural both intramural and extramural researchers out an online form requesting an electronic and extramural) could access death records access the NDI more easily. Led by the application and then wait less than a week for through the Social Security Administration Office of Behavioral and Social Sciences an email with instructions directing them to or the Center for Disease Control’s National Research (OBSSR), NIH entered into an the electronic application. After they submit Center for Health Statistics (NCHS)— agreement with the NCHS that became the application and supporting documents, which provided access to the National Death effective in January 2020. Now PIs can more there’s a two-to-three month wait for NDI Index (NDI)—the process was becoming easily request access to NDI data. What’s processing and approval. A PI can make more difficult, he said. Not only was the more, NIH will bear the expense. up to four requests in a calendar year; any process unwieldy, but the information was Staff scientist May A. Baydoun request exceeding $100,000 needs to be pre- often incomplete. In addition, researchers (National Institute on Aging), who approved by the NIH. had to pay for access. For example, the cost of frequently needs to access the NDI database For more information about the appli- accessing 1,000 patient records for a 10-year for her studies on dementia and Alzheimer cation process and other details about the period is about $1,850. But the costs quickly disease, was excited to have the NDI made National Death Index, go to https://www. escalate when researchers need information available for free to researchers like herself. cdc.gov/nchs/ndi/index.htm. on thousands of patients, depending on the The NDI assists investigators in size of the study. determining whether people in their studies Sunita Chopra is a visiting postdoctoral Intramural investigators do have other have died and provides the names of the fellow in the National Cancer Institute, means of obtaining death information, states where the deaths occurred, the dates where she studies radiation-responsive coding but only for patients on protocols at the of death, and death-certificate numbers. and noncoding RNA signatures in the blood NIH Clinical Center: the Biomedical Investigators can make arrangements with of whole-body-irradiated animal models.

6 THE NIH CATALYST NOVEMBER–DECEMBER 2020 TECHNOLOGY TRANSFER

NIDA Scientists Invent Mobile-Health Platform Mobile Technologies Revolutionize Care for People with Substance–Use Disorders BY DIPTADIP DATTAROY, NCI

Mobile-health technology drug misusers receiving methadone (mHealth) lets health-care providers treatment. The participants were given collect data on handheld electronic PalmPilots that they used to answer devices such as cell phones or tablets questions about drug cravings, stress, and use those data to predict the optimal and their location; and carried small timing for delivering treatments and GPS devices. The researchers also health-education messages to patients. used a novel tool, the Neighborhood Researchers at the National Institute on Inventory for Environmental Drug Abuse (NIDA) have developed Typology, to evaluate data in relation an mHealth platform for promoting to environmental cues (Drug Alcohol Kenzie Preston (left) has invented a mobile health technology that uses mobile devices to deliver warnings and therapeutic messages to psychological wellbeing in people Depend 134:22–29, 2014). help prevent recovering addicts from relapsing into drug use. suffering from opioid-use disorders: These initial experiments led to Mobile devices can monitor a patient’s developing a tool that can unobtrusively facility Biowulf. The mHealth platform location and intermittently ask questions collect data on smartphones and use them accurately predicted the probability of opioid about their psychological status, predict to predict drug cravings in people recovering craving or stress up to 90 minutes before the psychosocial stress, and deliver warnings from substance-use disorders before it’s too craving began (NPJ Digit Med 3:26, 2020). and automated therapeutic messages that late. In 2015, Preston along with NIDA This mHealth technology could can help prevent a recovering addict from researchers David H. Epstein, Matthew revolutionize clinical care for patients relapsing into drug use. Tyburski, and Massoud Vahabzadeh diagnosed with substance-use disorders, The journey to this innovation began developed an mHealth platform that posttraumatic stress disorder, depression, or in 2005 when NIDA Senior Investigator uses machine-learning technology and other mental-health disorders. Preston hopes Kenzie L. Preston (recently made scientist smartphones to continuously collect and that this mHealth platform would drastically emeritus) and her team began using a sort of monitor patient-specific ambulatory data, reduce health-care costs and improve patient real-time electronic diary—called ecological process it in a cloud-based server, predict outcomes. This tool could also be used to momentary assessment (EMA)—for 114 a user’s psychological status, and deliver study the effect of nongenetic influences, opioid-abusing outpatients being treated automated interventions when needed. Such such as environmental exposures, on human with methadone to report their activities and interventions include warning a patient in health. NIDA is seeking licensing and/or moods for up to 20 weeks. EMA had been recovery when they are at especially high risk codevelopment partners to further develop used to study tobacco addiction but rarely of experiencing a negative event that might and commercialize this mHealth platform. opioid addiction. The researchers reported cause them to relapse. Through numerous that the individuals used the mobile devices repetitions of processing such information, To learn about technology transfer activities to provide self-reported data daily and that the mHealth platform became increasingly at NIH, go to https://www.ott.nih.gov. In the data revealed behavioral patterns that accurate over time. A U.S. provisional patent addition, you can read the NIH Catalyst led up to drug craving and use. The findings application and an international patent story on Tech Transfer (May–June 2019 were published in the Archives of General application were filed on this technology issue) at https://irp.nih.gov/catalyst/v27i3/ Psychiatry (Arch Gen Psychiatry 66:88–94, in 2015 and 2016, respectively. In 2017, a news-you-can-use-technology-transfer. 2009). U.S. patent application was filed on the same In another study, published in 2014, invention. Diptadip Dattaroy was a postdoctoral fellow Preston’s team collected time-stamped In a recent clinical study, Preston and in the National Institute of Diabetes and Global Positioning System (GPS) data her team tested a prototype of this mobile Digestive Diseases and an NCI Technology and Ecological Momentary Assessment app on 189 outpatients being treated for Transfer Ambassador. He is now a fellow in ratings of mood, stress, and drug cravings opioid-use disorders and analyzed the data NCI’s Technology Transfer Center. at random times over 16 weeks of 27 urban using NIH’s High-Performance Computing

https://irp.nih.gov/catalyst 7 CATALYTIC RESEARCH Intramural Research Briefs

of achieving conception. Among the women The study found that,compared to who became pregnant, those who used opioids ordinary activities, the exercise test triggered around the time of conception were 1.5 times a faster onset of PEM, it lasted longer, and as likely to have a miscarriage as women who was more severe. More research is needed to had not. (NICHD authors: K.S. Flannagan, identify PEM subtypes, which may help guide S.L. Mumford, L.A. Sjaarda, J.G. Radoc, N.J. the development of targeted treatments. (NIH Perkins, V.C. Andriessen, J.R. Zolton, and E.F. authors: B. Stussman, A. Williams, J. Snow, A. Schisterman, Epidemiology 31:844–851, 2020) Gavin, R. Scott, A. Nath, and B. Walitt, Front [BY MEGAN KALOMIRIS, NIAID] Neurol 11: article 1025, 2020; DOI:10.3389/

CREDIT: NIAID CREDIT: fneur.2020.01025) NIAID: Inner elbow of a child with eczema before Roseomonas NHLBI: STUDY SHOWS DECLINE IN [BY DEBOLEENA MITRA GUHARAY] mucosa therapy (left) and after four months of treatment AWARENESS, TREATMENT, AND CONTROL (right). OF HIGH BLOOD PRESSURE CC, NICHD: MIGLUSTAT MAY DECREASE RISK NIAID, NCI, NCATS, NIEHS: EXPERIMENTAL In the past 15 years, there’s been a downward OF PNEUMONIA AND DEATH IN CHILDREN TREATMENT FOR CHILDREN WITH ECZEMA trend in awareness among Americans about AND ADOLESCENTS WITH NIEMANN-PICK NIH researchers found that an experimental hypertension (high blood pressure) and how DISEASE TYPE C1 treatment, with Roseomonas mucosa, to control and treat it, according to an NHLBI- A drug called miglustat seemed to stabilize modifies the skin microbiome, safely reduces funded study that included one intramural swallowing problems in children and the severity of atopic dermatitis (eczema), investigator. The study analyzed data from the adolescents with Niemann-Pick disease type decreases amounts of Staphylococcus aureus, National Health and Nutritional Examination C1 (NPC1) and decrease the risk of pneumonia a bacterium known to exacerbate eczema, and Survey of more than 18,000 American adults 18 caused by the aspiration of food or drink, increased quality of life for children as young and older with hypertension. The researchers according to an NIH study. NPC1, which has as three years old. Eczema, affects about 5% to found 70% of participants were aware of their no FDA-approved therapy, is a rare genetic 25% of children worldwide and is linked to an condition in 1999–2000; awareness increased disorder that causes a progressive decline increased risk of developing asthma, hay fever, steadily to 85% in 2013–2014 but declined to in neurological and cognitive functions. and food allergy. The researchers found that 77% in 2017–2018. Of adults with high blood The researchers used video fluoroscopy—a specific lipids produced by R. mucosa strains pressure, the number who controlled their digitized X-ray movie—to examine the ability of isolated from healthy skin can induce skin- condition increased from 32% in 1999–2000 miglustat to improve the swallowing function repair processes and promote the turnover of to 54% in 2013–2014, but then declined to 44% in 50 children and adolescents with NPC1. By skin tissue. (NIH authors: I.A. Myles, et. al., Sci in 2017–2018. (NHLBI author: L.J. Fine, JAMA the end of the three-year study, 36 patients had Transl Med 12: issue 560, eaaz8631, 2020) 324:1190–1200, 2020) been prescribed miglustat and 24 had not. A [BY AMRITA MANDAL, NICHD] [BY EMMA ROWLEY, NIAID] longitudinal analysis found that, compared with those not taking miglustat, those who took the NICHD: OPIOID USE MAY BE LINKED TO NCCIH, NIMH, NINR, NINDS: POST- drug had a 91% lower risk for deterioration of PREGNANCY LOSS EXERTIONAL MALAISE IN CHRONIC FATIGUE swallowing and a 72% lower risk of aspiration. Though physicians often prescribe opioids to SYNDROME The findings add to growing clinical evidence women of reproductive age, including after Myalic encephalitis/chronic fatigue syndrome demonstrating the efficacy of miglustat for a cesarean or vaginal delivery or following a (ME/CFS) is a debilitating, chronic disease treating NPC1. (NIH authors: B.I. Solomon, A.C. miscarriage, little is known about the effects of characterized by pain, cognitive difficulties, Smith, A.C., N. Sinaii, N. Farhat, M.C. King, L. the periodic use of such drugs in women who and severe fatigue. One of its major symptoms Machielse, and F.D. Porter, JAMA Neurol, 2020) were previously pregnant and wish to conceive is post-exertional malaise (PEM), the worsening [BY THU-LAN LILY NGUYEN, NCI] again. Researchers in NICHD examined the of symptoms after physical or mental activities. trends of conception and miscarriage in 1,228 NIH researchers conducted a study in which women and monitored prescription opioid 43 ME/CFS patients, divided into nine focus use through urine samples and self-reporting. groups (including five groups of people who Read more at: https://irp.nih.gov/catalyst/ For women who used opioids while trying to experienced PEM after a cardiopulmonary v28i6/research-briefs. conceive, there was a 29% reduced likelihood exercise test), described their experiences.

8 THE NIH CATALYST NOVEMBER–DECEMBER 2020 FEATURECATALYTIC RESEARCH COVID-19 Timeline at NIH (September–October 2020)

September 1: NIH launches a study to track the an app to order and pay for food from two Oct 8: A final report confirming remdesivir prevalence and impact of SARS-CoV-2 infection cafeterias. Food truck services continue, too. benefits for COVID 19 is published (N Engl J among approximately 16,000 pregnant women September 24: NIH scientists and others Med NEJMoa2007764, 2020). in seven low- and middle-income countries. announce their discovery of the genetic and October 12: Johnson & Johnson announces September 2: NIH announces $129.3 million immunologic underpinnings of some cases that it is pausing its phase 3 vaccine trial due in manufacturing support for new COVID- of severe COVID-19 (Science 370:eabd4570, to an unexplained illness in one participant 19 testing technologies as part of its Rapid 2020; Science 370:eabd4585, 2020). (trial resumes October 23). Also paused is the Acceleration of Diagnostics (RADx) initiative. September 29: NIH reports that the phase ACTIV-3 trial testing the Eli Lilly monoclonal September 9: NIH Director Francis Collins and 1 trial of Moderna’s investigational vaccine, antibody. The AstraZeneca phase 3 clinical trial U.S. Surgeon General Jerome M. Adams testify which was codeveloped with NIAID, shows that remains on hold in the United States but has on vaccines at a Senate Health, Education, the vaccine generates an immune response in resumed in other countries. Labor, and Pensions Committee hearing. adults over 70 years old (N Engl J Med 2020). October 12: NIAID launches the phase 2 September 10: NIH ACTIV (Accelerating September 30: As part of RADx, NIH awards ACTIV-5 Big Effect Trial, which is designed to COVID-19 Therapeutic Interventions and nearly $234 million to improve COVID-19 determine whether certain approved therapies Vaccines) initiative launches two of three testing for the underserved and vulnerable. or investigational drugs in late-stage clinical adaptive clinical trials of blood-clotting October 2-5: On October 2, President Donald development show promise against COVID-19. treatments for COVID-19. Trump announces that he and First Lady October 16: An NCATS-coordinated phase 3 September 11: NIH Director Francis Collins’s Melania Trump have tested positive for COVID- ACTIV-1 trial starts; it will evaluate safety and email to staff mentions that AstraZeneca 19. He is admitted to Walter Reed Medical efficacy of three immune modulator drugs in phase 3 investigational COVID-19 vaccine trial Center on October 3 and receives one dose of hospitalized adults. was paused because of an adverse event in experimental monoclonal antibodies, a several- October 16: NIH opens an exceptions process to the United Kingdom. He also announces the day course of remdesivir, and the steroid allow federal employees who are teleworking launch of a brief survey to determine how many dexamethasone. He is released on October 5. under challenging circumstances to apply to employees have telework situations that are October 5: Harvey Alter is awarded the 2020 voluntarily return to the physical workspace. not ideal and would like to work on-site. Nobel Prize in Physiology or Medicine for his Week of October 19: Moderna announces that it September 14: NIDA Director Nora D. Volkow contributions to the discovery of the hepatitis has reached its phase 3 vaccine trial enrollment coauthored a study that found that people with C virus that led to curative treatments and goal of 30,000 participants, with 42% of those substance-use disorders are more susceptible keeping the blood supply safe for transfusions. from high-risk groups. to COVID-19 (Mol Psychiatry 2020). October 5: Anthony Fauci is celebrated as October 23: Maryland’s Montgomery County September 14: Clinical Center begins offering the Service to America Medal 2020 Federal Chamber of Commerce announces that the saliva testing for asymptomatic employees. Employee of the Year. Ira Pastan is named 2020 Visionary of the Year Award goes to NIH. September 15: NIH awards contracts to develop the 2020 winner of the Paul A. Volcker Career October 28: Cell paper reports that NHLBI digital health technologies for COVID-19. Achievement Award for his discovery of drugs researchers discovered a biological pathway September 16: NIH funds community that successfully treat a rare form of leukemia that the novel coronavirus uses to hijack and engagement research efforts in areas hardest and holds promise for other cancers. exit cells as it spreads through the body. hit by COVID-19. October 6: The NIH RADx initiative advances October 29 and 30: The NIH/FDA COVID-19 September 22: NIH expands clinical trials to six new COVID-19 testing technologies. Research Workshop, held virtually, highlights test convalescent plasma against COVID-19. October 8: NIAID announces the start of a NIH’s and FDA’s extensive work on COVID-19. September 23: Fourth large COVID-19 vaccine phase 3 clinical trial to test whether remdesivir October 31: In a virtual celebration, NIH marks trial, to evaluate a single-dose vaccine, begins . plus a highly concentrated solution of the 80th anniversary of President Franklin September 23: NIAID Director Anthony Fauci antibodies that neutralize SARS-CoV-2 virus is Roosevelt’s October 31, 1940, dedication of testifies at a U.S. Senate Health, Education, safe and effective in hospitalized patients. the NIH campus. Labor, and Pensions Committee hearing on an October 8: NCI announces the launch of the update to the COVID-19: federal response. Serological Science Network for COVID-19 Read more at: https://irp.nih.gov/ September 23: The Office of Research Services (SeroNet), which aims to quickly increase catalyst/v28i6/covid-19-timeline-at-nih- announces that NIH staff on campus can use antibody testing capacity. september-october-2020

https://irp.nih.gov/catalyst 9 ALUMNI NEWS Bringing Precision Medicine to Neuroscience Profile: Andrea Pfeifer BY MICHAEL TABASKO research, or Lasker Award winner Robert pharmacology and toxicology led to working Gallo, whose work associated retroviruses on what mattered most to her—coming up with certain leukemias and lymphomas. with ways to diagnose and treat incurable The idea that cancer was a multifaceted diseases. disease deserving of targeted interventions She remembers her time at NIH fondly. was gaining traction. Meanwhile, over in “We worked like crazy, days and nights, Germany at the University of Würzburg, a for this unique opportunity to generate bright young scientist was considering where papers, feeling like there were no limits,” to start her career. she explained. “You could go out into the As luck would have it, two of Harris’s corridor and discuss your project with respected colleagues at the university a Nobel Prize–winning scientist such had been mentoring Andrea Pfeifer to a as Michael Bishop. It was an incredible Ph.D. in toxicology and cancer research: experience, the openness and sharing. I’ve Professor Hans Günter Neumann, the chair never seen anything like that again.” of the university’s Institute of Toxicology At NIH, Pfeifer helped create the first and Pharmacology and a pioneer in the immortalized human cell lines used as field of chemical carcinogenesis; and models for studying lung and liver cancer. Professor Dietrich Henschler, an expert These intentionally mutated cells divide in pharmacology and toxicology. They indefinitely and are still in use today and CREDIT: IMMUNE AC

Andrea Pfeifer, who trained at NIH, is now chief executive encouraged Pfeifer to explore a postdoctoral are licensed for applications ranging from officer of AC Immune SA, a Swiss biopharmaceutical company experience at NIH. medical research to drug testing. Pfeifer that she helped launch in 2003. Up to that point, Pfeifer’s studies were would later work for the food and beverage founded on a chemically based model of company Nestlé. In 1990 she set up a One of Andrea Pfeifer’s mottos treating chronic diseases. She had a different Cooperative Research and Development comes from Carl Zuckmayer, a German vision however, and her career trajectory Agreement with NIH to further develop writer who said, “One-half of life is luck; began to tilt toward a more precise molecular those cells for use in food-safety testing. the other half is discipline–and that’s the approach. “I wanted to link oncology with “She was very creative, rigorous with her important half, because without discipline molecular biology and this is why I choose scientific method, and had this inventive you wouldn’t know what to do with your Curt’s lab,” said Pfeifer. In 1984 she secured spark,” recalled Harris, who became Pfeifer’s luck.” In a career that arcs from the lab a grant and a fellowship, and she joined the scientific mentor and close friend. He joked, to corporate leadership and back again, NIH family as a postdoctoral fellow. “She was also very communicative and an Pfeifer knows a bit about what it takes to Growing up in Germany, Pfeifer was instigator of parties.” write your own success story. exposed to the more technical aspects of life: Harris’s lab celebrated its 25th The 1980s saw the dawn of precision “I changed tires, adjusted valves, and ran cars anniversary in 2006, long after Pfeifer medicine in oncology. At the National with my brothers.” She also had an uncle had left NIH. But she helped to Cancer Institute (NCI), Curt Harris’s at the University of Würzburg, Professor organize the event, bringing in alumni Laboratory of Human Carcinogenesis was Otto Volk, a physicist who stimulated and from across the globe. She recalled, at the forefront of molecular epidemiology. supported her curiosity in science. “We decided to gift Curt a painting They were pioneering novel approaches At age 11, things changed for Pfeifer by Swiss artist and physician-scientist to understand what factors make human when her father was diagnosed with Peter Cerutti for the party.” (Before cells mutate into cancer cells. Walking lymphoma, which ultimately pushed her pursing an art career, Cerutti was the halls of building 37, you would find toward the medical sciences. “It made me internationally recognized for his work Nobel laureate Michael Bishop, whose resilient, a survivor, made me a leader simply in cancer research and aging.) “The groundbreaking discovery of oncogenes because early on in life I had to take on painting was bigger than any airline had already changed the course of cancer greater responsibility,” she recalled. Studying would allow and I had to persuade a

10 THE NIH CATALYST NOVEMBER–DECEMBER 2020 ALUMNI NEWS

German government delegation to help to cognitive decline. me bring it from Switzerland to NIH.” While prion diseases (such as In 1989 Pfeifer left NIH having Creutzfeldt-Jakob disease) are rare, the published 26 papers (she now has over scientists recognized the same mechanism of 200). She returned to Europe to be with action in Alzheimer disease (AD) involving her ailing father and joined Nestlé at their amyloid-beta and tau proteins. Nearly Research Center in Lausanne, Switzerland, 50 million people suffer from dementia AC IMMUNE CREDIT: rising rapidly to become head of Nestlé worldwide, and AD is the leading cause. Global Research as she brought her Without an effective treatment, Pfeifer saw knowledge of molecular diagnostics to the a huge unmet need and an opportunity to food industry. Over the next 13 years she improve millions of lives. She left Nestlé and would transform the company’s research returned to her roots in medical research. Lab at AC Immune (Lausanne, Switzerland), a company with diagnostic and therapeutic product candidates to direction from chemistry to biology. Pfeiffer and her cofounders launched diagnose and treat neurodegenerative diseases. Pfeifer’s team sequenced the genome of AC Immune, a Swiss biopharmaceutical the bifidus bacterium, resulting in the first company, in 2003. They now have probiotic yogurt. “We discovered how food three diagnostic and nine therapeutic prevent the onset of AD in a high- can influence genetics, from skin health to product candidates to diagnose and treat risk population in the Aburrá Valley allergy prevention–all going in the direction neurodegenerative diseases. With a focus of Columbia who are genetically of precision nutrition,” she said. on early detection and accurate diagnosis, predisposed to AD. If the treatment She was translating science into business. the company leads the industry with their works, it would be the first to show how Using her multinational network Pfeifer tau protein programs. Brain-imaging AD might be prevented. expanded Nestlé’s research collaborations techniques, such as positron emission Pfeifer will tell you that she never with universities around the world. She tomography (PET) scans, can detect wanted to be a role model. But with time, cofounded a venture capital fund to bring abnormal tau concentrations decades before she realized that the success story around new projects into the company, exposing AD symptoms start. For example, a PET her career became an inspiration to other her to the world of start-up financing. It tracer (a radioactive drug used for diagnostic women. Woman are vastly underrepresented was around this time where she met the purposes) can identify abnormal tau which in the biopharmaceutical industry, yet Pfeifer men who would be the cofounders of her could then be treated with an appropriate excelled. Her secret? She credits remaining future company: Nobel laureate Jean-Marie vaccine, small molecule, or antibody. AC authentic, having honest mentors, and never Lehn, Claude Nicolau, Fred Van Leuven, Immune’s diverse pipeline continues to compromising the quality of her science. and the late NIH scientist and Lasker Award evolve through ongoing clinical trials. Staying true to herself has been a source winner, Roscoe Brady (National Institute Much like targeting specific oncogenes, of strength. “I worked extremely hard, and of Neurological Disorders and Stroke). the door is now open to identify maintained my [traditionally] feminine The four scientists approached Pfeifer neurodegenerative diseases before they start. qualities, like working with people and with a potential game-changer in the Pfeifer is reminded of her days at NCI. “We bringing people together,” she said. AC world of neuroscience. “They introduced a are at a crossroads because we can finally Immune is currently 52% women, well above technology that has the capability to target apply a precision approach in neuroscience the biopharma industry average. plaques and tangles in the brain caused by as we did 30 years ago in oncology,” she From scientist, to businesswomen misfolding proteins,” she explained. The said. “We can look into the brain, identify and entrepreneur, Pfeifer has had a truly researchers were mainly studying prions, the underlying pathology, and then actually remarkable journey. “It really goes back proteins that can trigger neighboring treat [neurodegenerative diseases] according to NIH,” she said. “I was exposed to proteins to misfold abnormally. A hallmark to that pathology.” multicultural approaches where many of several neurodegenerative diseases, In an NIH-funded study on healthy friendships and collaborations were formed mutated proteins can spread in a virus-like individuals, AC Immune is testing that still exist. They are still a source of manner throughout the brain and are linked whether the drug crenezumab can inspiration today.”

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

Resistance to the Plague CONTINUED FROM PAGE 1

before the Christian era. Kastner’s team used The researchers found that, compared mathematical modeling to estimate that two with cells from healthy control subjects, the FMF-causing mutations in the MEFV gene immune cells isolated from the blood of arose more than 2,000 years ago. They also people with FMF produced more interleukin found that people with the same mutations 1-beta (an inflammation-causing protein) in had stretches of identical DNA flanking response to Y. pestis infection. In addition, the mutation site. This set of DNA variants immune cells from people with only one tends to be inherited together and is called copy of the mutated MEFV gene (and who a haplotype. According to evolutionary usually do not develop FMF) were also theory, if there is a selective pressure such resistant to Y. pestis infection. Even mice as an infectious disease, a haplotype with that were genetically altered to have two mutations that protect humans in some way mutated MEFV genes had a clear survival

Dan Kastner was a co-author of a study that found that is conserved over the course of multiple advantage when infected with Y. pestis. genomic variants that cause familial Mediterranean fever generations. But if there is no selective The findings demonstrate the double- may also confer increased resistance to the bubonic plague. pressure, the haplotype is no longer useful edged sword that is evolution. “This is and is lost over time. In people with the certainly not the first example of a mutation copies of the mutated MEFV gene may be normal MEFV gene, the researchers didn’t in a recessive disease gene being protective a secret weapon against the bubonic plague. find a conserved haplotype. against an infectious agent…on the one Normally Y. pestis represses the function of But this evaluation didn’t explain hand…but on the other hand causing a pyrin in healthy individuals and in so doing what was causing the natural selection to human disease,” said Kastner. suppresses the body’s inflammatory response increase the frequency of MEFV mutations Another example of a genetic mutation to the plague. But the mutated MEFV genes in Mediterranean populations. that is protective yet causes disease is the prevent the ability of Y. pestis to interfere Kastner’s group suspected Y. pestis as beta-globin gene, which when mutated with the normal function of pyrin. exerting a potential selective pressure on causes sickle-cell anemia but also confers NHGRI Scientific Director Dan mutations in the pyrin gene because 1) resistance to malaria. Kastner, a senior author on the paper, Y. pestis releases a toxin called YopM that Still, evolution has done what is best has studied FMF since 1985 when, as an inactivates pyrin—it makes sense that for humans. Despite a small number of NIH rheumatology fellow, he treated an humans would evolve a mutation in the pyrin people having two mutant MEFV copies Armenian patient who had the disease. gene that increases its resistance to YopM; and developing FMF, more have only one Kastner’s group first considered that natural 2) Y. pestis was an incredibly strong selective copy and are resistant to the bubonic plague. selection played a role in today’s prevalence pressure—the bubonic plague wiped out a Moving forward, Kastner plans to of FMF because of its unusually high third of Europe’s population in the 14th consider how interactions between hosts and carrier frequency (proportion of people century; and 3) Y. pestis has been able to microbes influence the evolution of other in a population who have only one copy shape the human genome for an incredibly genetic diseases. “The host is just half of of a mutant gene). The carrier frequency long time—it was around during the 6th the equation,” said Kastner. “There’s this of MEFV mutations in Mediterranean century Justinian plague and the 14th whole other world, the microbial world.” populations is about 10%. century Black Death. “It was in Jewish populations, Arab, Ethan Smith, a postbaccalaureate fellow in E. DEL AGUILA III, NHGRI III, AGUILA DEL E. Turkish, [and] Armenian,” said Kastner. the National Institute of Nursing Research, “It didn’t seem like something that would is working on clinical studies involving happen just by chance.” If it did, the carrier biomarkers for traumatic brain injury. When frequency would be much lower. he completes his training in 2021, he expects To provide evidence for natural selection, to attend graduate school for social work. the researchers analyzed the genomes An illustration depicting specific genomic variants passed of 2,313 Turkish people and 352 ancient down to succeeding generations. archeological samples including 261 from

12 THE NIH CATALYST NOVEMBER–DECEMBER 2020 FROMFEATURE THE ANNALS OF NIH HISTORY Glimpses of History through Uniform Patches and Coloring Books Two New Exhibits at the NIH Clinical Center BY DEVON VALERA, OFFICE OF NIH HISTORY

Two fairly new exhibits in the NIH introduced children to complicated ideas illustrated by Jenene Warmbier and Ellen Clinical Center (CC)—one on uniform but can also aid historians in understanding Vassy. Warmbier began illustrating the book patches and another on coloring books— changing attitudes and perspectives at the in 1975 when her two-year-old daughter reveal the more colorful side of the CC’s NIH throughout history. was diagnosed with neuroblastoma, history. Coloring books have been prevalent at a cancer that targets early nerve cells. Patches: Thanks to Margaret Conant NIH since at least the 1960s. The oldest on When her daughter was being treated (in CC’s Radiological and Imaging Sciences display, The Friendly Clinical Center Coloring at the Ohio State University Children’s Department), who donated patches to Book, introduced children to the NIH and Hospital (Columbus, Ohio), Warmbier the Office of NIH History and Stetten potentially foreign concepts such as medical began to draw what she saw around her, Museum, more than 50 uniform patches clothing, hospital rooms, and occupational compiling images of the potentially scary are now on display. The exhibit is on the first therapy. Despite the commendable intentions things that children can encounter during floor of Building 10 at the end of the central of this coloring book, it unfortunately reveals cancer treatment. Warmbier created a corridor near the Phlebotomy/EKG Clinic. the biases of the time. Diversity wasn’t a remarkably compassionate and friendly A familiar sight on lab coats and consideration back then—children were image of the hospital featuring a diverse uniforms, these patches identified different all presumed to be white and the doctors representation of races, sexes, and abilities. departments and units that operated within exclusively referred to as “men.” This lack Ellen Vassy, a nurse at the Children’s the CC. Patches were designed either by the of diversity changed, however, with the Hospital, contributed text. This book was Medical Arts branch or by NIH employees introduction of The Clinical Center Coloring first used at the Children’s Hospital before competing in design competitions and Book published nearly 30 years later. It was being modified and reprinted by NCI in revealed the personalities and perspectives created by Wendy Schubert of the CC’s 1982. (Sadly, Warmbier’s daughter died 20 of the divisions they represented. Patient Education Working Group and months after her diagnosis.) The patches are vibrant, playful, represents a more diverse panel of both These stories and many more are tucked thoughtful, and, at times, mysterious. patients and clinicians. within the halls of the Clinical Center. We Anesthesiology’s patch takes the phrase Another noteworthy coloring book is invite you to explore these two new exhibits “counting sheep” literally and features two Hospital Days, Treatment Ways: Hematology- as well as the many others the Office of NIH fluffy white sheep leaping over a fence. The Oncology Coloring Book, written and History and Stetten Museum has installed patch for the National Cancer Center’s throughout the NIH campus. (NCI’s) Hyperthermia Unit shows a crab being boiled, referencing both Maryland’s culinary specialty as well as the zodiac sign BOTH: MICHELE LYONS, OFFICE OF NIH HISTORY Cancer in a clever visual pun. More curiously, though, the CC itself is represented by, of all things, a duck. Why? We’re not quite sure ourselves. If you have any insights into this mysterious duck’s meaning, please let Michele Lyons know ([email protected]. gov). We’d be delighted to include its history alongside these patches. Coloring books: The second exhibit, on the second floor near the cafeteria, considers the history of a familiar object–the coloring One of the coloring books in the display in the book. From explaining the roles of doctors Mark Riewestahl, an exhibit intern at the Office of NIH NIH Clinical Center: Hospital Days, Treatment History and Stetten Museum, near the display of Clinical Ways: Hematology-Oncology Coloring Book. and nurses to illustrating what operating Center patches that he designed. rooms look like, these books not only

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

Singing Dogs CONTINUED FROM PAGE 1

is physically similar to and thought to be Moreover, the discovery of free-living the predecessor of the singing dogs. In highland wild dogs may provide greater 2016, the New Guinea Highland Wild insight into the genomics of vocalization, Dog Foundation, in collaboration with a field that has previously relied on the study the University of Papua (West Papua, of birdsongs. According to Heidi Parker, an Indonesia), led an expedition to Indonesia NHGRI staff scientist who led the genomic and found 15 highland wild dogs. In a analysis, it is believed that dogs developed follow-up field study in 2018, blood samples barking as a means to mimic human speech were collected from three of the dogs and after they were domesticated. This belief analyzed by Ostrander’s lab in NHGRI. is supported by the fact that wolves do not The DNA analysis revealed an ancestral bark, and neither do highland wild dogs, relationship between the highland wild dog which seldom encounter people. The and the New Guinea singing dog. They are highland wild dogs are unique in that they essentially the same breed, according to the neither bark nor howl but have developed

Elaine Ostrander’s team confirmed via genomic analysis researchers. The genomes are not identical, a completely different form of vocalization that there is an ancestral relationship between the New however, because the populations have been with their singing, the purpose of which is Guinea highland wild dog and the New Guinea singing dog, long thought to be extinct in the wild. physically separated for several decades and yet unknown. due to inbreeding among the captive New “We think that this could be a really Guinea singing dogs. great comparison [with] both wolves and studying these dogs may help scientists “There’s an opportunity to reinvigorate [with] modern dogs to understand what understand how human vocalization the conservation populations and bring changed in [the highland wild dogs] to developed. back the true New Guinea singing dog” change the tones, basically to hold these “One of the cool things about genomics by establishing breeding programs, said very sort of musical notes versus a barking is that once you do the genome sequence Ostrander. “It’s one of the many examples sound,” said Parker. The genome sequences of something, you can go back to that data of how the Human Genome Project benefits collected in this study can be searched for over and over and over to look at different a lot more than just humans.” the genes responsible for vocalization and traits,” explained Elaine Ostrander, NIH those genes can be compared with the ones Distinguished Investigator and senior author found in the human genome; the differences of the paper. “We went to it to test and see if and variations could reveal more about what these were, in fact, the New Guinea singing these genes do. “It could even give us some dogs. But we can go back to it again and indication of how people sing.” see if we can find the genes responsible for The researchers also hope that their vocalization.” studies will provide insights into how The New Guinea singing dog was first deficits in human vocalization occur and studied in 1897. In the late 1960s, when it offer clues that could lead to treatments. was clear that the breed was endangered, eight of the dogs were brought to the United Journal article referred to in the article: States for conservation purposes. There are Proc Natl Acad Sci USA 117:24369-24376, 200–300 of these dogs in captivity today, 2020; DOI:10.1073 (https://www.pnas.org/ but the effects of inbreeding in such a small content/117/39/24369). pool of individuals for many generations has resulted in loss of genomic variants that Natalie Hagen, a postbaccalaureate research existed in their wild counterparts. Heidi Parker and her dog Hattie. Parker led the genomic fellow in the National Center for Advancing More recently another wild dog analysis in the study. The discovery of free-living highland Translational Sciences, is performing population, called the “New Guinea wild dogs may provide greater insight into the genomics of vocalization, a field that has previously relied on the pharmacokinetics studies of novel drug highland wild dog,” has been sighted. It study of birdsongs. candidates. In 2021, she plans to pursue a Ph.D.

14 THE NIH CATALYST NOVEMBER–DECEMBER 2020 FEATURE

Joan Steitz’s WALS Lecture on Viral Noncoding RNA Taking RNA from Historic Origins to Modernity BY FRANCES FERNANDO NICHD

Joan Steitz leads and inspires by Medical Science for “pioneering discoveries example, with her infectious passion for all in RNA biology, generous mentorship things RNA. As a young college student, of budding scientists, and vigorous and she had seen female medical doctors but passionate support of women in science.” never a female professor heading a lab. Exploring RNA: Steitz has been She did not anticipate building a career as studying RNA since the field’s nascency a woman molecular biologist. in the 1960s and has loved seeing the Her interest in molecular biology began developments and exciting questions in the 1960s when she was a work-study answered since. “The RNA field did not intern in Alex Rich’s laboratory at the exist, and [I] was privileged enough to be one Massachusetts Institute of Technology of the committee of people who established (MIT, in Cambridge, Massachusetts). the RNA Society,” said Steitz who was its Rich, who played an important role in the first vice president and president-elect in Yale professor Joan Steitz delivered a virtual WALS lec- ture on “Viral Noncoding RNAs: Approaching Answers.” discovery of nucleic acid hybridization, had the 1990s when the society was established. worked with Nobel laureate Francis Crick She has contributed to monumental to solve the structure of collagen. advancements in the RNA field through decay of PAN RNA by engaging the end Steitz earned her undergraduate degree multiple discoveries, notably of the sites, section called the polyA tail. One of Steitz’s in chemistry in 1963 (from Antioch College sequences, and mechanisms for mRNA postdocs later determined that the structure in Yellow Springs, Ohio) and then went on binding to ribosomes and of single- forming the RNA was the longest stretch to train with two Nobel laureates herself— nucleotide ribonucleic proteins and their role of triple helix ever documented in RNA. Crick and James Watson, who together in splicing systems. From this basic RNA Steitz told the story of how three NIH had first described the DNA double-helix research comes exciting and tangible payoffs investigators—Gary Felsenfeld, David structure in 1953 and won the Nobel Prize in in medicine because 60% of genetic diseases Davies, and her mentor, Rich—predicted Physiology or Medicine in 1962. She was the have splicing-system defects. exactly this structure…back in 1957. first female graduate student to join Watson’s WALS lecture: On September 23, Steitz believes that further structural lab at Harvard University (Cambridge, 2020, Steitz’s gave a virtual lecture on and molecular understanding of RNA Massachusetts) and completed a Ph.D. in her research on viral noncoding RNAs will be critical in the field’s future of biochemistry and molecular biology in 1967. (ncRNAs), which play critical roles in the elucidating RNA’s diverse functions. Her postdoctoral training in cell biology regulation of gene expression. Her focus With her pioneering RNA work, she has was with Crick at the Medical Research has been on gamma-herpesviruses such enthusiastically forged paths forward for new Council Laboratory of Molecular Biology as Kaposi sarcoma-associated herpesvirus scientific discoveries, medical contributions, in Cambridge, England. (KSHV, the cause of the most common and women in science. Incidentally, both Rich and Watson cancer afflicting AIDS patients), Epstein- had NIH ties: Rich as a section chief in Barr virus (which can cause mononucleosis), To watch Joan Steitz’s WALS talk, go to https:// physical chemistry (1954–1958) and Watson and others. Her investigations of videocast.nih.gov/watch=38678 (HHS only). as the first director of the National Center polyadenylated nuclear (PAN) RNA, which for Human Genome Research (1989–1992). is in cells infected by KSHV, has led to the Frances Fernando is a postbaccalaureate fellow Today, Steitz is a Howard Hughes realization that it contains an RNA element in the National Institute of Child Health and Medical Institute Investigator and the (called the element for nuclear expression, Human Development. After completing her Sterling Professor of Molecular Biophysics or ENE) that’s needed for the nuclear training in 2021, she plans to pursue a doctorate and Biochemistry at Yale. She’s won accumulation of RNA transcripts. in public health to work on integrative global numerous awards including the 2018 Lasker- Her group discovered that ENE health issues and human rights. Koshland Special Achievement Award in elements prevent the degradation and

https://irp.nih.gov/catalyst 15 NEWS YOU CAN USE Cyber Health Checkup: Don’t Be Phish Food! NIH Cyber Safety Awareness Campaign BY SUSAN CHACKO, CIT

Cybersecurity is one of those peer reviewer at a university shared their realize is that we are a connected community, annoyances that your institute’s informa- NIH grant-review login information with and [anyone] could end up being one of the tion technology (IT) people take care of, a grant applicant, who was then able to breaks in the system.” right? access reviews and identify the reviewers of Scientists might feel that a security- Wrong. That might have been the case a their own grant application. NIH takes the monitoring program, or “agent,” running decade or two ago, but now, keeping NIH’s confidentiality and integrity of its vast grant- on their laptop is slowing the computer employees, patients, and systems safe from review process very seriously, and there are down or that they are being spied on, said cyberattacks is a responsibility for everyone consequences from such misbehavior. When Ryan Dale, a senior scientist at the National who accesses NIH data and systems. Did the breach was discovered, the resulting Institute for Child Health and Human you know than more than 99% of the emails investigation led to the resignation of both Development (NICHD). He certainly coming into NIH are spoofing or phishing researchers from their institutions. understands the pressure to get research attempts (messages that masquerade as a NIHers may have noticed an increasing done, but as NICHD’s scientific information trusted entity and try to trick recipients into number of emails, announcements, and officer, he also appreciates the importance sending money or clicking malicious links) articles about cybersecurity at NIH over of protecting the big cyber target that is the or spam (unsolicited advertising email)? the past few months. These are part of the NIH. Thousands of vulnerabilities—old, Every day, 23 million emails are blocked NIH Cyber Safety Awareness Campaign, unsafe operating systems, poorly configured by the central NIH email filters and 36 an Optimize IT Security initiative, which software, and suspicious downloaded million web connections to suspicious sites aims to raise awareness of the real-life material—are identified each day by NIH’s are stopped at the NIH firewall. risks to NIH if cybersafe behaviors are not security agents. Last year, one spoof didn’t get blocked: implemented and embraced. Collaborating safely: There are a lot of Several employees received an email Cybersecurity and research: Many collaboration tools for sharing photos and purporting to be from NIH Director scientists have seen IT security as an obstacle data, but they are not all NIH approved Francis Collins asking them to use their to research but are beginning to understand or safe to use. The NIH Technology government purchase cards to buy gift cards that the barriers are necessary for the Availability Guide (NTAG) provides a list that supposedly would be distributed for protection of their work and NIH resources, of approved tools that will enable research employee recognition awards. Luckily, a said NCI staff scientist Art Shaffer. As a collaborations while protecting NIH digital careful recipient alerted the NIH IT Service member of the Optimize IT team, he brings assets. NIH has a robust set of collaboration Desk. The NIH information security team a bench researcher’s perspective to the work. and file-sharing tools that are approved and confirmed the spoof, removed the email Before COVID-19 forced many NIH available for use including Box, Skype for from the inboxes of hundreds of employees, employees to work from home, interactions Business, Jabber, Microsoft Teams, and and determined that the director’s email between scientists were face-to-face with Zoom. Using collaboration or file-sharing had not been hacked. Without this alert, little cyber risk. Now “I can’t just take a flash platforms that have not been approved for thousands of federal dollars might have been drive with my two gigabytes of data over to use by your information system security scooped up by the cyber criminals. my buddy’s computer at the other end of the officer (ISSO) and are not listed on the It’s not just taxpayer money that is at lab,” said Shaffer. Instead, the data need to be NTAG may expose NIH to cyber threats, stake but also patient medical records, transferred securely over the NIH network breaches, or data loss and should not be personal employee information, and vital using a tool such as NIH Box. used. If you don’t already have access to a research data. Data sharing “is fundamental to the tool listed on NTAG, contact the NIH IT Cyber risks don’t just come from the NIH mission, but we need to be able to do Service Desk for assistance. Before using outside. One seemingly minor infraction that safely,” reiterated Robert Balaban, the any collaboration or file-sharing tool that is is sharing login credentials with a friend scientific director of the National Heart, not listed on NTAG, contact your ISSO to or colleague. The potential for damage—to Lung, and Blood Institute, during a recent ensure it is safe to use. If emailing sensitive or systems, to personnel, and to biomedical virtual panel discussion about cyber safety confidential information, encrypt the emails research—is huge. A few years ago, a and COVID-19. “The important thing to or send them via NIH Secure Mail. And if

16 THE NIH CATALYST NOVEMBER–DECEMBER 2020 THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS New SIG: Sexual and Gender Minority (SGM) Health Scientific Interest Group you need a collaboration tool that is not on the NTAG list, work with your ISSO to The recently established Sexual Director. While regular activities for discuss your needs and have tools properly and Gender Minority Health Scientific this SIG will be led by members of the assessed before use. A single cybersecurity Interest Group (SGM Health SIG) is IRP, the SGMRO will provide guidance incident has the potential for widespread interested in supporting a range of by selecting and inviting extramural consequences; do not compromise your data biomedical, clinical, behavioral, and scientists to present scientific lectures or that of others, use NIH approved tools, social science research to advance to the group. SGMRO will also assist and when in doubt, reach out to your ISSO the health of all sexual and gender IRP researchers leverage resources to for guidance. minority (SGM) populations, with a better engage in SGM health research Report anything suspicious: In general, specific interest in the disease areas and help identify mentors for trainees. “Don’t be afraid to report something” that and health conditions that affect these The SGM Health SIG is open to seems unusual, said Jothi Dugar, chief individuals. all (including NIH intramural and information security officer at the Center The SIG will 1) connect individuals extramural investigators, as well as for Information Technology, who is leading trained in different scientific disciplines people from other federal agencies the Cybersecurity Awareness Campaign. engaged or interested in conducting and area universities). The SIG will Be on the lookout for suspicious emails, or SGM health research; 2) provide have regularly scheduled meetings computers acting weird (crashing frequently intramural researchers and trainees a every two to three months and hold or showing popup ads, for example). “We’re venue to share and receive feedback on an annual retreat. Meetings will not going to be coming after you for clicking their research and discuss publications feature presentations by invited NIH on a link. We want to take care of the related to SGM health; and 3) provide staff, extramural researchers, and SIG situation and provide guidance and training.” opportunities for career development, members, and discussions about research Cyber safety needs to be a priority networking, and community ideas and relevant publications. for all employees, integrated into their engagement. For more information and to join day-to-day jobs. The “protective shell of SGM populations include but are the SGMHEALTH_SIG LISTSERV IT infrastructure armors NIH against not limited to individuals who identify email list, which will share meeting cyberattacks on a daily basis,” said Schaffer. as lesbian, gay, bisexual, asexual, announcements and other information, go But all of us have a part to play as well. transgender, Two-Spirit, queer, and/ to https://oir.nih.gov/sigs/sexual-gender- or intersex; individuals with same-sex minority-health-scientific-interest-group. To find resources mentioned in this article go or -gender attractions or behaviors For questions, contact the chair, Erik to NIH Cyber Safety Awareness Campaign and those with a difference in sex Rodriquez ([email protected]). website, go to https://ocio.nih.gov/InfoSecu- development; and those who do not rity/Pages/CyberSafety.aspx. To reach the self-identify with one of these terms NIH IT Service Desk go to https://myitsm.nih. but whose sexual orientation, gender NIH Scientific Interest Groups (SIGs) are gov or call 301-496-4357, 866-319-4357 (toll- identity or expression, or reproductive assemblies of scientists with common research free), or 301-496-8294 (TTY). development is characterized by interests; communicate via LISTSERVs; sponsor nonbinary constructs (not identifying symposia, poster sessions and lectures; provide Susan Chacko, who is a scientist on the as either man or a woman) of sexual mentoring and career guidance for junior Biowulf cluster staff at the Center for orientation, gender, and/or sex. scientists; help researchers share the latest Information Technology, came to NIH as a The SGM Health SIG is a techniques and information; and more. Most postdoc in 1992. She leads a team of scientists partnership among the NIH institutes, SIGs welcome interested non-NIH scientists, who install and maintain scientific programs centers, and offices, the Intramural too . For more information and a list of SIGs, go on Biowulf, helps intramural researchers Research Program (IRP), and the to https://oir.nih.gov/sigs. implement large-scale computational research Sexual and Gender Minority Research projects, and provides one-on-one support. Office (SGMRO) in the Office of the

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Recently Tenured

CHRISTINA ANNUNZIATA, NCI- T.C. “KELVIN” CHOI, NIMHD TAE-WOOK CHUN, NIAID HEIDI H. KONG, NIAMS DA-TING LIN, NIDA CCR

CHRISTINA ANNUNZIATA, M.D., PH.D., growth and survival. NF-kappa-B is or refractory ovarian cancer. We found NCI-CCR a protein complex that controls DNA that avelumab demonstrated antitumor Senior Investigator and Head, Translational transcription, cytokine production, and activity and acceptable safety in these Genomics Section, Women’s Malignancies cell survival. Aberrant NF-kappa-B patients (JAMA Oncol 5:393–401, 2019). Branch, Center for Cancer Research, National signaling has been identified in tumors More recently, we have focused on Cancer Institute of epithelial origin including breast, colon, enhancing the innate immune system Education: Georgetown University College lung, and ovarian carcinomas. to overcome the immune-suppressive of Arts and Sciences, Washington, D.C. (B.S. My lab’s genomic profiling and environment of the abdominal cavity, in biology, Ph.D. in pathology); Georgetown functional screens identified both where ovarian cancer grows. We completed University School of Medicine, Washington, downstream targets and upstream a phase 1 clinical trial using interferons D.C. (M.D.) regulators of this pathway, defining alpha and gamma to stimulate monocytes Training: Resident, Department of Internal subgroups of patients whose cancers that we injected directly into the patients’ Medicine, Georgetown University School depend on NF-kappa-B and opening abdomens (J Transl Med 16:196, 2018). of Medicine; Medical Oncology Fellow and up possibilities for novel therapies to This therapy is very promising in that later Research Fellow, Medical Oncology treat ovarian cancer. I am conducting it could be a platform on which to layer Branch, NCI several clinical trials to better understand personalized immunotherapy approaches. Came to NIH: In 2002 for training both predictive and pharmacodynamic Ongoing studies of patient samples Outside interests: Cooking; cycling; and markers of treatment response. One of from this trial will help us to design the doing yoga my earlier clinical trials used a synthetic next steps in improving this therapy as Website: https://irp.nih.gov/pi/ small molecule called birinapant to well. christina-annunziata block NF-kappa-B signaling and induce apoptosis in ovarian cancer (Cancer Research interests: Ovarian cancer 122:588–597, 2016). This study led us to T.C. “KELVIN” CHOI, PH.D., M.P.H., NIMHD accounts for more deaths than any other identify other pathway inhibitors that are Senior Investigator, Social and Behavioral cancer of the female reproductive system, synergistic in killing ovarian cancer cells. Group, National Institute on Minority resulting in over 15,000 deaths annually. We are about to open a new clinical trial Health and Health Disparities Most patients respond to platinum- with the combination of small molecules Education: The Hong Kong Polytechnic based chemotherapy, but more than that inhibit two pathways. University, Hong Kong (B.Sc. in 70% of people with advanced ovarian A second focus of my lab and clinic physiotherapy); University of Minnesota at cancer relapse within 24 months. My is immunotherapy for ovarian cancer. I Minneapolis (M.P.H. in community health lab has identified a subset of ovarian participated in a recent study to assess education and Ph.D. in epidemiology) cancer cell lines that are dependent on the efficacy and safety of avelumab in 125 Training: Attended training institutes the NF-kappa-B signaling pathway for women with previously treated recurrent through NIH’s Office of Behavioral and

18 THE NIH CATALYST NOVEMBER–DECEMBER 2020 COLLEAGUES

SUSAN L. MOIR, NIAID KEISUKE (CHRIS) NAGAO, JOHN NGAI, NINDS KANDICE TANNER, NCI-CCR STEPHEN WHITEHEAD, NIAID NIAMS

Social Sciences Research and NIDA; especially four-year college programs. The knowledge gained from these Fundamentals of Team Science and the In another study, we found that youth investigations will be used to construct Science of Team Science through the exposure to secondhand smoke was more effective anti-tobacco interventions National Science Foundation and the associated with later lower academic and messages that are tailored to smokers University of Central Florida performance (Am J Prev Med 58:776–782, of disadvantaged populations, and public- Before coming to NIH: Various positions 2020). health interventions for other health-risk including assistant professor at the My team is also investigating how behaviors. University of Minnesota School of Public tobacco companies’ marketing strategies Health, Division of Epidemiology and cultivate and foster tobacco use among Community Health; clinic manager and adolescents and adults and how the effects TAE-WOOK CHUN, PH.D., NIAID physiotherapist, Cosmo Physiotherapy differ by demographics and socioeconomic Senior Investigator and Chief, HIV Center (Hong Kong) status (SES). In one study, we found that Immunovirology Section, Laboratory of Came to NIH: In 2013 as a Stadtman adults of lower SES were more likely to Immunoregulation, National Institute of Investigator in NIMHD be exposed to tobacco discount coupons, Allergy and Infectious Diseases Outside interests: Enjoying nature (hiking, and this exposure was related to the Education: California State University biking, canoeing, and camping) and being progression and continuation of smoking at San Bernardino, California (B.S. in the father of a synchronized ice skater (Nicotine Tob Res 20:1095–1100, 2018). biology); Johns Hopkins University School Website: https://irp.nih.gov/pi/kelvin-choi We are also investigating the physiological of Medicine, Baltimore (Ph.D. from the and neurological responses to tobacco- Biochemistry, Cellular and Molecular Research interests: I am interested marketing materials among smokers; what Biology Graduate Program) in the interconnected and potentially we learn will inform both how best to Training: Research fellow, Laboratory of reciprocal relationships between the regulate these materials and design anti- Immunoregulation at NIAID social determinants of health and tobacco tobacco messages. Came to NIH: In 1997 for training; became a exposure and use, and the social and In addition, we are examining how to staff scientist in 2001, an associate scientist environmental factors that explain these leverage marketing principles (including in 2009, and an Earl Stadtman Investigator relationships. For example, we found price, placement, promotion, and products) in 2016 that smoking influences sleep quality in to reduce tobacco-use disparities, Outside interests: Hanging out with Canada youth, which can affect their academic particularly among young adults. I am Geese on campus and Panda Cam watching performance and subsequent college currently working with collaborators to Website: https://irp.nih.gov/pi/ enrollment. We also found that cigarette develop a computer simulation that can tae-wook-chun smoking during the high school years forecast the potential impact of tobacco– is associated with a lower likelihood of marketing regulations on tobacco-use enrolling in post-secondary education, disparities. CONTINUED ON PAGE 20

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Research interests: A l t h o u g h virus, CD4 (N Engl J Med 375:2037–2050, demonstrated how the skin microbial antiretroviral therapy reduces the amount 2016; N Engl J Med 380:1535–1545, 2019). communities can vary based on the specific of human immunodeficiency virus Additional clinical trials are currently location on the body. We found that (HIV) in blood, it does not completely being developed to explore the possibility despite the skin’s exposure to the external eradicate the virus in infected individuals. of achieving complete remission of environment, its microbial communities Persistently infected CD4 T-cell reservoirs HIV in infected individuals through were largely stable over time. have long half-lives and could contribute the administration, twice a year, of a In addition, we know that the skin to viral rebound when antiretroviral combination of long-acting anti-HIV microbiome can be distinguished in therapy is interrupted. Treatment for HIV, antibodies and antiretroviral drugs. certain skin diseases and with specific therefore, has to be continued through immunodeficiencies. While we found life. My group’s research focuses on 1) that disease flare-ups in patients with delineating the role of viral reservoirs HEIDI H. KONG, M.D., M.H.SC., NIAMS atopic dermatitis are linked with higher in the pathogenesis of HIV disease; 2) Senior Investigator, Cutaneous Microbiome percentages of Staphylococcus aureus or examining host and viral factors that and Inflammation Section, Dermatology Staphylococcus epidermidis, patients with a contribute to the maintenance of HIV Branch, National Institute of Arthritis and rare primary immunodeficiency (DOCK8, reservoirs; and 3) developing therapeutic Musculoskeletal and Skin Diseases; Adjunct or dedicator of cytokinesis 8, deficiency) strategies aimed at achieving durable Investigator, Cancer and Inflammation have higher proportions of DNA viruses virologic control in infected individuals Program, Center for Cancer Research, on their skin. in the absence of antiretroviral therapy. National Cancer Institute These studies highlight how the host We conduct comprehensive genetic, Education: Stanford University, Stanford, shapes, and in turn may be shaped by, the immunologic, and virologic analyses of T California (B.S. in biological sciences); skin microbiome. Our current efforts are cells in diverse cohorts of HIV-infected Baylor College of Medicine, Houston (M.D.); focused on deeper investigations of these individuals. In so doing, we are addressing Duke University, Durham, North Carolina host-microbial interactions. fundamental pathogenic questions, (M.H.Sc.) such as elucidating mechanisms of viral Training: Residency and chief residency persistence; examining the role of the in Dermatology, Duke University; clinical DA-TING LIN, PH.D., NIDA host immunity in containment of viral research fellow, NCI’s Dermatology Branch Senior Investigator and Chief, Neural replication; and evaluating promising novel Came to NIH: In 2005 for training Engineering Section, Behavioral Neuroscience therapeutic agents in both ex vivo and in Outside interests: Spending time and Branch, National Institute on Drug Abuse vivo settings (J Infect Dis jiaa270, 2020); traveling with family; baking; reading Education: University of Science and J Clin Invest 129:4832–4837, 2019; PLoS Website: https://irp.nih.gov/pi/heidi-kong Technology of China, Hefei, China (B.S. in Pathog 14:e1006792, 2018). biology); University of Texas Health Science In addition to our bench research, we Research interests: My group integrates Center at San Antonio, San Antonio, Texas have conducted several phase 1 clinical advanced genomics and translational (Ph.D. in cell biology) trials in close collaboration with the research expertise in dermatologic Training: Postdoctoral fellow, Department NIAID HIV clinic, with the ultimate disorders to study human skin microbes of Neuroscience, Johns Hopkins University goal of developing safe, effective, and and gain insights into the pathogenesis (Baltimore) scalable therapeutic strategies that of inflammatory skin diseases. My lab’s Before coming to NIH: Assistant professor, would allow HIV-infected individuals to work has advanced our understanding of The Jackson Laboratory (Bar Harbor, control viral replication without having human skin microbial communities. Maine) and Department of Medicine, Tufts to use antiretroviral drugs daily. Among In particular, we study the diversity University School of Medicine (Boston) the multiple therapeutic trials we have and complexity of bacterial, fungal, Came to NIH: In 2013 as chief of NIDA’s conducted over the past several years, two and viral communities in healthy Optical Imaging Core were directed at blocking HIV by using skin and in eczema from patients Outside interests: Playing soccer monoclonal antibodies that bind either with atopic dermatitis and with Website: https://irp.nih.gov/pi/da-ting-lin the virus or the human receptor for the primary immunodeficiencies. We have

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Research interests: I am studying the SUSAN L. MOIR, PH.D., NIAID responsible for various manifestations neural circuit mechanisms involved in Senior Investigator and Chief, B-Cell associated with HIV disease, including long-term drug addiction and relapse. My Immunology Section, Laboratory of hypergammaglobulinemia (excess laboratory is developing and applying in Immunoregulation, National Institute of globulins in the blood), inadequate vivo optical imaging methods, as well as Allergy and Infectious Diseases response to vaccination, altered computational methods for data analysis, Education: University of Guelph, Guelph, homeostasis associated with lymphopenia to measure neural-circuit dysfunction that Ontario, Canada (B.S. in biological science, (lower than normal number of may lead to long-term substance abuse minor in biotechnology); Université du lymphocytes) that occurs in late HIV and cause patients in recovery to relapse. Québec, Institut Armand-Frappier, Laval, disease and AIDS, reduced responsiveness Neuroscientists and engineers are Québec, Canada (M.Sc. in virology and of B cells due to immune exhaustion and increasingly interested in studying immunology); Université Laval, Québec City, other inhibitory effects, and inefficient neuronal activities at the microcircuit Québec, Canada (Ph.D. in microbiology and antibody responses due to altered level and are pushing the limits in immunology) maturation of B cells in lymphoid tissues developing miniature in vivo imaging Training: Postdoctoral visiting fellow, NIAID (Nat Rev Immunol 9:235–245, 2009; Nat systems. This interdisciplinary effort Came to NIH: In 1996 for training; became Immunol 19:1001–1012, 2018; Sci Transl has led to a widespread use of wearable staff scientist in 2006, associate scientist in Med 11:eaax0904, 2019). miniature microscopes, which are 2010, and Stadtman Investigator in 2015 Another long-term goal is to apply constantly improving in size, cost, spatial Outside interests: Spending time with her our knowledge of B cells in HIV to other and temporal resolutions, and signal-to- family; enjoying outdoor activities; and immune-mediated diseases, particularly noise ratio. being inspired by market-to-table-style primary immune deficiencies in which B Right now my group is developing cooking to share meals with others cells play a pathogenic role. imaging systems that can visualize Website: https://irp.nih.gov/pi/susan-moir neural activity from deep-brain regions in animals. Such systems are becoming Research interests: The primary focus of KEISUKE (CHRIS) NAGAO, M.D., PH.D., NIAMS more important for understanding neural- my research program is to study the role Senior Investigator and Head, Cutaneous encoding mechanisms underlying cognitive of B cells in the pathogenesis of human Leukocyte Biology Section, National Institute of functions. We independently developed immunodeficiency virus (HIV) disease, with Arthritis and Musculoskeletal and Skin Diseases a miniScope (a miniature fluorescence the ultimate goal of filling gaps in knowledge Education: Keio University School of microscope), an imaging system that about humoral immunity against the virus. Medicine, Tokyo, Japan (M.B., M.D., Ph.D. in allows the simultaneous recording of This knowledge is critical to the development microbiology) activity of hundreds of neurons in deep- of an effective antibody-based vaccine and Training: Residency in dermatology, brain regions of freely behaving mice. The for the advancement of immunotherapeutic Keio University School of Medicine, and miniScope expands the realm of possible interventions in HIV-infected individuals. in anesthesiology, Tokyo Dental College behavioral experiments for in vivo imaging My group’s approach involves assessing Hospital, Tokyo, Japan; visiting fellow, studies (Neuron 92:202–213, 2016 and transcriptional, phenotypic, and functional Dermatology Branch, Center for Cancer Neuron 100:700–714.e9, 2018). We are attributes of B cells that circulate in the Research, National Cancer Institute continuing to explore in vivo deep-brain peripheral blood and those that reside in Before returning to NIH: Senior assistant imaging of neuronal circuit activity and tissues, particularly lymph nodes and bone professor, Department of Dermatology, Keio refining techniques to measure neuronal marrow. University School of Medicine dysfunction. A major focus of our research also Came to NIH: In 2005–2008 for training; includes identifying and characterizing returned in 2014 as Stadtman Investigator various subsets of B cells—in the blood Outside interests: Reading; exercising and tissues of healthy individuals— Website: https://irp.nih.gov/pi/ that are overexpressed at various stages keisuke-chris-nagao

of HIV infection. We have shown CONTINUED ON PAGE 22 that several of these subsets may be

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JOHN NGAI, PH.D., NINDS cells. Upon severe injury, these Research interests: I am a dermatologist Senior Investigator, National Institute of adult tissue stem cells are activated with a longstanding interest in skin Neurological Disorders and Stroke; Director and go on to reconstitute all of the immunology and immune-mediated of NIH BRAIN Initiative cellular constituents of this sensory diseases. My research program aims to Education: Pomona College, Claremont, epithelium. The regenerative capacity advance our knowledge on how the skin California (B.A. in chemistry and zoology); of the olfactory epithelium therefore functions as an immunological organ. Harvard Medical School, Boston (Program presents a powerful and experimentally We study mechanisms that underlie skin on Cell and Developmental Biology); accessible paradigm for elucidating the immunity and host-microbiota crosstalk California Institute of Technology, Pasadena, mechanisms regulating neural stem- during health and inflammatory diseases. California (Ph.D. in biology) cell function. Over recent years, we have identified hair Training: Postdoctoral fellow, California We are using a variety of approaches follicles as control towers of skin immunity: Institute of Technology and Howard Hughes to unravel the molecular and cellular the follicles guide the localization of skin- Medical Institute/Columbia University mechanisms regulating olfactory stem resident leukocytes and enhance their College of Physicians and Surgeons (New cells and olfactory neurogenesis in the survival by producing chemokines and York) mouse. For example, we use conditional cytokines. In turn, leukocytes, such as the Before coming to NIH: Professor of genetic knockouts to investigate the innate lymphoid cells, communicate with Neurobiology, Department of Molecular and roles of certain transcription factors hair follicles to tune the balance of the Cell Biology, and Coates Family Professor and intracellular signaling pathways microbiota on the skin surface. of Neuroscience, Helen Wills Neuroscience in promoting stem-cell self-renewal, We have also determined that the Institute, University of California at Berkeley proliferation, and differentiation. alteration of the host-microbial relationship (Berkeley, California) As a complementary approach, we drives atopic skin inflammation. The Came to NIH: In 2020 also apply single-cell transcriptomic skin of atopic dermatitis (AD) patients Outside interests: Doing photography; and single-cell epigenomic analyses is commonly colonized with Staphylococcus enjoying food and wine to identify the genetic and epigenetic aureus. For decades, scientists have debated Website: https://www.ninds.nih.gov/ programs that both define and whether this bacterium contributes to AD About-NINDS/Who-We-Are/staff/ regulate olfactory neurogenesis during pathophysiology. By generating an AD John-Ngai regeneration. mouse model that recapitulated S. aureus Our studies provide a model susceptibility in humans, we demonstrated Research interests: The generation for understanding the mechanisms S. aureus to be a crucial driver of skin of cellular diversity in the nervous regulating neural stem cells and lay the inflammation, thereby providing an system requires the specification groundwork for the future development answer to a longstanding question. and differentiation of a multitude of treatments and therapeutics We leverage advances in sequencing of cell lineages from multipotent to ameliorate tissue damage and technologies to understand disease progenitor cells. The regulatory degeneration in the nervous system. pathophysiology directly in humans. programs governing this process remain Diseases of interest include primary incompletely characterized, however, immunodeficiencies and intractable in part because of the difficulty in immune-mediated diseases such as severe studying neuronal progenitor cells in drug hypersensitivities in which we use their native environments. My lab uses single-cell RNA sequencing to tailor the mammalian olfactory epithelium as personalized medicine. We will continue a model for addressing this challenge. to use approaches in experimental models Primary sensory neurons in the and expand our studies on human diseases olfactory epithelium are continuously to understand core and translatable regenerated throughout adult life via mechanisms that regulate skin immunity the proliferation and differentiation and facilitate host-microbial symbiosis. of multipotent neural progenitor

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KANDICE TANNER, PH.D., NCI-CCR analysis, and mechanical mapping—and Nile virus, and Japanese encephalitis virus Senior Investigator and Head, Tissue the use of home-built optical tweezers—in (JEV). We are particularly focused on Morphodynamics Section, Laboratory of a zebrafish model. This work was the first developing a tetravalent dengue vaccine Cell Biology, Center for Cancer Research, demonstration that physical properties of called TV003. Because previous infection National Cancer Institute blood vessels can regulate how metastasizing with one DENV serotype can increase the Education: South Carolina State University, tumor cells in vivo select organs to migrate risk for serious disease after infection with Orangeburg, South Carolina (B.S. in to (Cell Syst 9:187–206.e.a6, 2019). a different serotype, a successful vaccine electrical engineering technology and We also found that after tumor cells will need to protect against all four DENV physics); University of Illinois at Urbana- leave the circulation, they must adapt to a serotypes. Champaign, Urbana, Illinois (M.S. in physics; tissue environment of different properties I have long-standing collaborations Ph.D. in physics) from that of the primary tumor. Using 3D with investigators from Johns Hopkins Training: Postdoctoral fellowships at culture models, we have uncovered a novel University (JH, Baltimore) and the University of California at Irvine (Irvine, mathematical formulation that decribes the University of Vermont (UVM, Burlington, California), University of California at coupling of 3D microscale cell extracellular- Vermont). Among our many studies of Berkeley (Berkeley, California)/Lawrence matrix mechanics (Proc Natl Acad Sci U S A the dengue vaccine TV003, one was a Berkeley National Laboratory (Berkeley, 116:14448–14455, 2019). Moving forward, pivotal clinical demonstration showing California) we wish to leverage our understanding of that TV003 elicited complete protection Came to NIH: In 2012 as a Stadtman tissue biophysics to define a biomarker that against DENV in a human challenge Investigator will be predictive of the site of the secondary model: 21 vaccine recipients were protected Outside interests: Kickboxing; running; lesion. and 20 placebo recipients were not (Sci reading Transl Med 8:330ra36, 2016). In another Website: https://irp.nih.gov/pi/ clinical study with JH, UVM, and NIAID kandice-tanner STEPHEN WHITEHEAD, PH.D., NIAID colleagues, we demonstrated that TV003 Senior Investigator and Chief, Arbovirus was fully potent as a single-dose vaccine Research interests: My lab focuses Vaccine Research Section, Laboratory of Viral (J Infect Dis 214:832–835, 2016); and we on understanding the metastatic traits Diseases, National Institute of Allergy and also showed that TV003 is well tolerated that allow tumor cells to colonize Infectious Diseases and highly immunogenic in subjects with secondary organs. Some exciting findings Education: Brigham Young University, flavivirus exposure before vaccination in the field of mechanobiology have Provo, Utah (B.S. microbiology; M.S. in (PLoS Negl Trop Dis 11:e0005584., 2017). demonstrated that biophysical properties microbiology); Oregon State University, In addition to recent clinical studies in such as cell shape, mechanical phenotype, Corvallis, Oregon (Ph.D. in microbiology) Thailand and Taiwan, a key phase 3 study topography, hemodynamic forces, and Training: Postdoctoral fellow, Rockefeller of TV003 is nearing completion in Brazil. pressure can modulate how genes are University (New York) and NIAID; senior The vaccine technology has been licensed activated and silenced in key processes staff fellow, NIAID to seven companies and institutes across involving cell growth, migration, invasion, Came to NIH: In 1995 for training; became a the world for further development and and metabolism. We have developed staff scientist in 1999 commercialization. biophysical tools and novel animal models Outside interests: Loves spending time My group has also made important to understand how physical cues from the with his family; working in the garden; and advancements with other flaviviruses. For tissue microenvironment drive organ-specific cooking. He holds a certificate in Chinese example, we are developing live attenuated metastasis. We aim to understand what cuisine. ZIKV and JEV vaccines that are compatible drives organ targeting and secondary-tumor Website: TBD with the DENV vaccine, thus enabling outgrowth. simultaneous vaccination against DENV In one study, we discovered that the Research interests: My lab is developing and either ZIKV or JEV. Novel vaccine physical properties of blood vessels regulate and evaluating vaccines against mosquito- candidates for ZIKV are being developed organ selectivity in vivo. We combined borne flaviviruses, which include dengue with Alexander Pletnev in NIAID’s intravital imaging, vessel-topographical virus (DENV), Zika virus (ZIKV), West Laboratory of Infectious Diseases.

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