NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 25 ISSUE 3 • MAY-JUNE 2017

The NIH Big Read Microscopy as Masterpiece A Review of Inaugural Event With A Beautiful Way to Study Neurons Writer Siddhartha Mukherjee BY LAURA STEPHENSON CARTER BY HAYLEY RAQUER, NIAID

Excitement built throughout NIH this spring when NIH’s inaugural Big Read program had dozens of people reading and discussing Siddhartha Mukherjee’s new book, The Gene: An Intimate History. Then, on April 17, the Big Read culminated with an appearance by the Pulitzer-Prize-winning author himself to discuss his book and meet his fans. It was his second book visit to NIH, the first being in 2011 to talk aboutThe MARK STOPFER, NICHD Emperor of All Maladies: A Biography of Cancer, the bestseller that won him the Pulitzer Prize and was the basis of a PBS film on cancer. Although he carries obvious credentials within literary circles, Mukherjee’s This composite image shows two neurons, in the locust brain, that process olfactory information. background is rooted firmly in the biomedical sciences. In 1992, he graduated Perhaps only a scientist can find the beauty within a locust brain. An from Stanford University (Standford, image—looking like mirrored, psychedelic-colored mushrooms—captured by Mark California) with a B.S. in biology. He Stopfer—reveals the intricacies of neurons in the brain of the Schistocerca Americana had undergraduate research experience locust. The image is one of several included in the “Microscopy as Masterpiece” in the lab of Nobel Prize winner Paul digital exhibit at the Strathmore arts center in North Bethesda, Maryland. NIH Berg. After completing his Ph.D. at and the Strathmore partnered to develop the exhibit, which complements the “Arts Oxford University (Oxford, England) as a and the Brain” lecture series, and features beautiful brain microscopy images and Rhodes scholar, Mukherjee matriculated videos created by NIH-supported researchers. to Harvard Medical School (Boston) where he received his M.D. in 2000. Now an CONTINUED ON PAGE 11 assistant professor of medicine at Columbia University in New York City, he splits his CONTENTS time as an oncologist, researcher, and science FEATURES • |1| Big Read |1| Microscopy as Masterpiece |6| How Oxidative Stress Kills Cells writer. |7| Delayed Walking and Autism |12| WALS Superstars |14| Profile: Teresa Przytycka Given his extensive curriculum vitae DEPARTMENTS • |2| DDIR: Population-Based Research |3| SIG Beat: Light Microscopy; and contributions to science, medicine, and Scientia et Philosophia |4| Training Page/News Everyone Can Use: Data-Science Skills |5| New

CONTINUED ON PAGE 10 Methods: Mouse-Behavior Monitoring System |8| Research Briefs |11| Announcements: Kudos |16| Colleagues: Recently Tenured |19| Abbreviations |20| Back Page: More Cajal on Campus FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

Population-Based Research Improving Public Health BY MICHAEL GOTTESMAN, DDIR

In the past I have pointed out how and environmental factors that increase Today, expectant mothers take folate laboratory-based research at the NIH has the incidence of cancer. NCI scientists supplements, and bread is supplemented changed the practice of medicine. An have discovered a substantial percentage with folate to ensure adequate maternal even greater impact on public health can of the human genetic syndromes that concentrations for normal fetal development. be attributed to the epidemiological studies predispose one to cancer, including the As a result, there has been a dramatic drop done by NIH scientists or as collaborations eponymous Li-Fraumeni syndrome that is in neural-tube defects in the United States between intramural and extramural due to inherited p53 mutations that lead to and several other countries. investigators. Such population-based cancers in multiple organ systems. People NICHD epidemiologists have made intramural programs have been established who carry mutations that predispose them other important contributions. They were in about half of the institutes and centers, to cancer can be counseled to undergo earlier the first to show an association between including the NCI, NICHD, NIAID, and more frequent screening to improve the maternal diabetes and poor fetal outcomes. NIEHS, NIMH, NHLBI, NHGRI, likelihood that cancer can be discovered in They also showed that participation in NEI, NIA, NIDDK, and NIMHD. an earlier, more treatable stage. formal swimming lessons was associated Epidemiologic studies provide rigor- DCEG scientists also did many of with an 88 percent reduction in the risk of ous statistical evidence of the association the early epidemiological studies that drowning in children aged one to four years between human behavior or environmental showed the relationship between human old. (Drowning is a common cause of death circumstances and disease that may moti- papillomavirus (HPV) infection and cervical in childhood in many parts of the world.) vate more detailed mechanistic studies to and oropharyngeal cancer. Their work That demonstration has influenced the advice enhance prevention or suggest other inter- pointed to the need for an HPV vaccine, that pediatricians give parents and will, we ventions to ameliorate disease and disability. which was developed by John Schiller and hope, lead to universal swimming lessons. Such studies use a wide range of research Douglas Lowy in NCI. Some studies have been reassuring; for designs, often involve multidisciplinary and NCI has also demonstrated example, NICHD epidemiologists have multi-investigator collaborations, and may associations between environmental shown that children conceived by assisted generate mechanistic data that support find- exposures, such as medical X-rays and reproductive technologies have the same ings from laboratory-based studies. computed-tomography scans, and an growth and developmental trajectories as By way of example, allow me to cite increased incidence of cancer. These children conceived without treatment. studies that have led to changes in the studies have resulted in changes in medical NIEHS has also contributed to studies practice of medicine and have made obvious practice that should reduce the incidence of pregnancy and human development. improvements in the public’s wellbeing. of radiation-associated cancers. The observation that up to 25 percent of These studies represent a tiny percentage Another distinguished population- embryos fail to survive six weeks (before of the population-based studies done at the health program at the NIH is NICHD’s women know they are pregnant) came from NIH and have been chosen only to illustrate Division of Intramural Population Health an NIEHS study, as did the finding that how powerful such studies can be. Research, which will be celebrating its 50th by age 50 up to 80 percent of black women The focus of NCI’s Division of Cancer anniversary soon. Epidemiologists in this and 70 percent of white women have uterine Epidemiology and Genetics (DCEG), program study human populations across fibroids. For black women, especially, the founded more than 50 years ago by Joseph the lifespan. Twenty-five years ago, NICHD earlier development of fibroids has significant Fraumeni Jr. (who has just retired but will scientists in collaboration with researchers public-health implications. continue as a scientist emeritus at the NIH; in Ireland found an association between For NHLBI, the iconic Framingham congratulations, Joe!), has been on genetic neural-tube defects and folate deficiency. Study represents a comprehensive effort to

2 THE NIH CATALYST MAY-JUNE 2017 FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS

enumerate the risk factors that contribute LIGHT MICROSCOPY NEW SIG: SCIENTIA ET PHILOSOPHIA to the development of atherosclerotic The Light Microscopy Interest Group (LMIG), The Scientia et Philosophia Interest Group cardiovascular disease. Most of the which aims to build a bridge between NIH seeks to foster and expand the knowledge seminal observations about the association biologists and microscopists, informs the NIH and understanding of the NIH research among smoking, high blood pressure, community about cutting-edge research in community and staff of the philosophical lipid abnormalities, obesity, and diabetes light fluorescence microscopy and about avail- foundations of the scientific endeavor. In and heart disease came from the rigorous able resources, both extramural and intramural. an interdisciplinary, open, and inclusive envi- population-based studies conducted by the NIH researchers are at the leading edge of ronment, the group promotes an exchange intramural leaders of the Framingham study this fast-growing field. Do you want to learn of knowledge in a diversity of fields and and their many extramural colleagues who about madSTORM, the super-resolution tech- topics including the philosophy, origins, and contributed. Additional studies to test the role nique multiplexed antibody size–limited direct foundations of science; logic and rational- of these factors in more diverse populations stochastic optical reconstruction microscopy ism; cosmology and cosmogony; biology are underway, but the primary methodology developed in NCI’s Center for Cancer Research and biogeny; ethics, meta-ethics, and meta- came from the Framingham study. and applied to localization of 25 proteins simul- physics; and history of philosophy (classical With three generations of study taneously in activated T cells? Or how about to modern). participants, decades of clinical data, and innovative dyes for single-molecule imaging The group stresses how our current a treasure trove of molecular and DNA- permitting bright, stable, and reliable labeling empirical scientific projects in basic and clini- methylation data from thousands of of protein fusions to HaloTag, SNAP tag, and cal research are inseparably tethered to these participants analyzed by whole-genome CLIP tag; a new antibody-based drug-delivery philosophical underpinnings and are strength- sequencing, gene-expression profiling, method based on “uncaging” of biologically ened when clearly grounded on a strong microRNA profiling, proteomics, and active molecules by near-infrared light; or philosophical foundation. A good working metabolomics, the Framingham study is genome organization and its cell-to-cell varia- knowledge of the philosophical foundations of at the forefront of a burgeoning new field tion revealed by high-throughput fluorescence science and the limits of rationalism allow for of molecular epidemiology that will provide in situ hybridization? better formulation of scientific experimental insights into the next generation of risk factors If you are interested, come to the LMIG design, model construction, and parsimonious for cardiovascular and many other diseases. seminars to learn about innovative microscopy extraction of inferred conclusions. There are many other examples of techniques and their application to biomedical This SIG is open to intramural profoundly important observations made by research. The aim is to demonstrate applicabil- investigators, staff, and trainees as well NIH population scientists that have improved ity of the state-of-the art microscopy to tissue- as to extramural affiliates and academic public health. The ones cited here give you and cell-biology problems. Presentations scientists and clinicians outside the NIH. a flavor of the important contributions that include biological data and in-depth descrip- Activities will include regular discussion the NIH has made to this field. tion of appropriate microscopy techniques. meetings, internal and external speakers, Although different from laboratory- or To get the mailings, join the LIST- and webinars. To join the SCIENTIA_ET_ clinic-based mechanistic studies, population- SERV at https://list.nih.gov/cgi-bin/ PHILOSOPHIA LISTSERV, go to https:// based research has had a substantial effect wa.exe?SUBED1=light_micro_interestl&A=1. For list.nih.gov/cgi-bin/wa.exe?A0=SCIENTIA_ on public health. And, it’s important to more information, contact the LMIG moderators ET_PHILOSOPHIA-L.For more information, note, that the work is not possible without a Christian Combs ([email protected]) and contact the group moderator, Peter Leeds team-science approach. Research teams often Tatiana Karpova ([email protected]). ([email protected]). include biostatisticians, health behaviorists, and clinicians. The celebration, this May, of a half- century of studies on population health The Light Microscopy Interest Group focuses on innovative microscopy techniques and their application to at NICHD provides us with an occasion biomedical research. Shown: A technique called Förster to take stock of our many successes and to resonance energy transfer (FRET) reveals mammalian cells transformed with the fusion protein cyan fluorescent ensure that we will support rigorous and protein (CFP)–yellow fluorescent protein (YFP) before vigorous population studies at the NIH and after acceptor (CFP) photobleaching.

in the future. T.S. KARPOVA, NCI

https://irp.nih.gov/catalyst 3 THE TRAINING PAGE/NEWS EVERYONE CAN USE

Lasso Your Data Consider Adding Data-Science Skills to Your Biologist’s Toolbox BY CRAIG MYRUM, NIA

Think back to when you still had “Classes range from the hands-on train- So should all trainees learn a coding a basic cell phone. You could make calls, ing available through the NIH Library language? “Familiarity with a command- you could text, you could play some and Foundation for Advanced Education line interface such as Linux is a basic literacy games. It got the job done. When you in the Sciences to the ‘Current Topics in skill in any technical field because a large got your first smart phone, its capabilities Genome Analysis’ series.” (For the latter, and increasing proportion of modern data probably seemed endless. How could you check out those lectures at http://genome. and tools are intractable with GUI [graphi- possibly go back to your “dumb” phone gov/CTGA2016). Online coding classes cal user interface] tools,” explained Busby. now? are growing tremendously in popularity. (For coding-illiterate folks out there, GUI For day-to-day data organization and Many of them are free or at least reasonably is the graphical display, rather than purely analysis, we are all probably quite comfort- priced for the quality of content you receive. textual, that allows us to use the computer able with Excel. But biology’s complexity NIH scientific interest groups (SIGs) hardware in a user-friendly way.) is now being reflected in complex sets of and LISTSERV electronic mailing lists are Whether or not you should learn coding data, so computational analyses that require also valuable resources. “One of the best may depend on the types of data that you coding skills are becoming the norm. With things about the Bioinformatics SIG is that want to analyze and your overall career tra- any hope, we biologists will soon look back people can post specific questions on the jectory. “It certainly is advantageous to have at Excel in the same way we do old cell LISTSERV. Questions are usually answered these skill sets to facilitate data analysis,” phones. within the hour,” said Ben Busby, genomics said Baxevanis. “But in many instances, Learning coding sounds like a daunt- outreach coordinator at the National Center what is more important is being able to use ing task to many of us. Our excuses for not for Biotechnology Information. the analysis resources that are out there in learning a coding language often resemble Efforts are underway to set up a related an intelligent fashion, taking the time to justifications for not learning a foreign interface for general data science. Busby and understand what these predominantly Web- language: “I get by without,” “I don’t have colleagues are also establishing an NIH-wide based resources can do and how they do time,” or “I’m not good at those kinds of data-science mentorship program to facilitate it—and that they should never treat these things.” But enhancing your data-science one-on-one mentorship and training. Several resources as a ‘black box’! The same way it’s skills (machine learning, data visualization, NIH institutes and centers have their own important to understand the underpinnings and especially coding) can be your ticket to bioinformatics cores that offer similar train- of any laboratory-based method, the same better personal and professional opportuni- ing and mentoring opportunities. applies for all things computational.” ties. Biomedical scientists’ ability to work For example, Supriyo De, staff scientist with model organism databases, structural at the National Institute on Aging, and RESOURCES data, clinically relevant variation data, omics colleagues recently launched the Biomedical data, or any other publicly available set of Data Science Initiative, which offers • NIH Library: https://nihlibrary.nih.gov/ “big data”—a virtual treasure trove—can seminar-type overview training, hands- resourcetraining/Pages/default.aspx help answer important research questions. on training for smaller focus groups, and • LISTSERVS & SIGs: https://datascience. Although most basic biological graduate integrated one-on-one teaching for fellows nih.gov/community/datascience-at-nih/sigs programs do not require coding classes, the analyzing data from their own projects. #title3 demand for data-science training has not All trainees can also reach out to Intra- • Computational Biology Scientific gone unnoticed at the NIH. mural Research Program faculty members Focus Area: https://irp.nih.gov/ “All [intramural] trainees have quite a who use computational approaches in our-research/scientific-focus-areas/ few resources at their disposal if they want their own work. “Many of us very much computational-biology to start to tip-toe into the computational enjoy mentoring,” said Baxevanis. “People • More online at: https:// space,” said Andy Baxevanis, head of should feel free to reach out when they need irp.nih.gov/catalyst/v25i3/ the National Human Genome Research some advice and guidance regarding their the-training-page-news-everyone-can-use Institute’s Computational Genomics Unit. projects.”

4 THE NIH CATALYST MAY-JUNE 2017 NEW METHODS

Lights, Camera, Mouse Action NIH Develops New Mouse-Behavior Monitoring System BY SWAGATA BASU

with a Python-based Graphical User Inter- face (GUI) which allows the user to preview video streamed from the cages and set up multi-cage experiments. Action: The most advanced feature of SCORHE is its ability to extract measures

GHADI SALEM, CIT SALEM, GHADI of mouse activity and behaviors. The SCORHE video (center) is analyzed automatically to produce a per-frame 3D-pose estimate (right) and behavior label SCORHE team has developed algorithms (left). The pose estimates (estimates of the mouse’s position) and behavior labels are used to generate full circadian- cycle profiles of activity and behavior. to accurately estimate the 3D position of the mouse despite the fisheye-lens distortion. The algorithms also measure bouts of Automated video-based monitoring SCORHE, do not integrate with vivarium predefined behaviors including walking, of laboratory mouse behavior is getting cage-racks. grooming, food-interaction, drinking, more efficient thanks to a team of NIH “SCORHE was designed to demonstrate climbing, and resting. The measures researchers led by Ghadi Salem, a staff the feasibility of integrating large-scale, provide detailed time-resolved locomotion scientist in the Signal Processing and video-surveillance methods in animal and behavior profiles for the mouse over Instrumentation Section (SPIS) at NIH’s facilities by means of efficient mechanical multiple circadian cycles. Center for Information Technology. The design leveraging a nontraditional camera The system can be used for phenotypic new “System for Continuous Observa- configuration,” according to the group’s characterization of animal models, behav- tion of Rodents in Home-cage Environ- publication in Behavioral Research Methods ioral and activity profiling, circadian and ment” (SCORHE) is composed of custom (Behav Res Methods 47:235–250, 2015). sleep-pattern monitoring, and therapeutic video-acquisition and analysis tools that “This [system] eliminates issues with trials. “Since behavior is an expression of can quantify mice activity and behavior moving the mice from their home cage overall health, our system can demonstrate for short and long (multi-day) durations to the testing environment, which can be improvements in health and quality of life, while the mice are housed within a typical stressful for them,” said principal investiga- said SCORHE team member John Dennis, home-cage. The specialized hardware is tor Alexxai Kravitz (National Institute of who is the director of the Division of Veteri- space efficient, compatible with vivarium Diabetes and Digestive and Kidney Dis- nary Services at the FDA Center for Biolog- cage racks, and animal-facility-user friend- eases), who is validating SCORHE’s ability ics and Evaluation Research (Silver Spring, ly. The advanced software algorithms to analyze obesity-related behaviors such as Maryland). “And it can make animal stud- output animal-behavior measures. locomotion and feeding. ies more humane by identifying and report- Video monitoring of animals in their Lights: To obtain both daytime and ing humane endpoints automatically.” home cages is noninvasive and provides more night-time measures of behavior, SCORHE As work is underway to produce the information about behavior than observa- uses near-infrared illumination, which pro- latest set of prototypes, the SCORHE tions of mice using running wheels or vides consistent image quality without dis- team is preparing for NIH intramural tripping photobeam detectors. SCORHE— turbing the animals’ light and dark cycles. researchers to collaborate on beta testing which can monitor the day-to-day health of Camera: The SCORHE units employ (on their specific application) to produce mice, provides advanced behavioral screen- inexpensive Raspberry PI digital cameras a more refined and capable system. The ing, assesses the short- and long-term effects fitted with fisheye lenses. Although the fish- development will be kept open-source to of experimental treatments—avoids disrupt- eye lenses cause images to be distorted, they widely serve the NIH intramural program ing circadian rhythms, does away with the are key to the compact design and ventilated- and the greater scientific community. need for mice to become acclimated to test rack integration. SPIS engineers developed environments, and allows for night-time software for continuous high-frame-rate cap- More information can be found at the project measurements. Commercially available ture of digital video from multiple cameras website: https://scorhe.nih.gov. systems can be expensive and, unlike to over long durations. The software comes

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

NIEHS Team Reports How Oxidative Stress Kills Cells A Key to Understanding the Origins of Some Human Diseases BY ROBIN ARNETTE, NIEHS

Breaking DNA: Wilson said human lung cells, they trigger a similar that cellular mitochondria, which are ROS response by macrophages. specialized energy-producing machines The macrophages use the same that fuel cells, also produce molecules mechanism to get rid of invaders. But in that harm cellular DNA and proteins. this case, the oxidative stress eventually These harmful molecules, known as leads to fibrosis, which is the thickening reactive oxygen species (ROS), can or scarring of tissue seen in chronic alter the chemical composition of the lung disease. Wilson mentioned other compounds used to build DNA, as well conditions, such as cataracts, cardiovascular as DNA itself. If the DNA building disease, and some neurodegenerative blocks are not restored to their original disorders, that are also linked to the effects shape, or if DNA is structurally modified of oxidative stress. due to ROS, the DNA can break, Understanding the mysterious THOMAS DEERINCK, U. OF CALIFORNIA, SAN DIEGO Mitochondria are specialized energy-producing machines triggering the cell to self-destruct. mitochondria: Wilson said the research that fuel cells, but they also produce reactive oxygen species “When ROS-modified compounds described in the new paper demonstrates (ROS) molecules that harm cellular DNA and proteins. Shown: mitochondria (with diagonal striations) from the are incorporated into a DNA strand, they a subtle way cells can accommodate heart muscle cell of a rat. cause frayed ends that can’t be properly the damage ROS inflicts on them. The glued together during DNA repair,” self-destruction of an individual cell Wilson said. “This gap or break in DNA as a result of oxidative stress is a less Humans need energy to function, can initiate cell death.” extreme outcome than the result of so it might be hard to imagine how Double-edged sword: The pressure exposure to a strong oxidizing agent, a naturally occurring process that that ROS places on cells is called such as bleach. In that case, all of the generates power for the body can oxidative stress, and it happens all the cells in the mix—both the body’s cells also harm its cells. But it does, noted time. The body takes advantage of the and the pathogens—would die. Samuel Wilson and members of killing power of ROS in a series of steps “We know that the mitochondria his DNA Repair and Nucleic Acid known as innate immunity, which is the probably produce the majority of ROS in Enzymology Group, in the National natural immunity a person is born with. a cell,” said NIEHS mitochondrial expert Institute of Environmental Health For example, Wilson explained that Bill Copeland, who was not involved in Sciences (NIEHS). when a bacterium enters the body, a white this research. “So fully understanding Based on work done by Wilson’s blood cell activates a special immune cell their function may lead to the root of research fellow Melike Caglayan, the called a macrophage. The macrophage human illness.” team determined more details about how douses the bacterium with ROS. Just as this particular type of damage leads to ROS causes breaks in human cellular and This article is adapted, with permission, DNA strand breaks and, ultimately, cell mitochondrial DNA, it will go to work from the March 2017 issue of Environmental death. The scientists used biochemical breaking the bacterium’s DNA. That Factor: https://www.niehs.nih.gov/news/ and cell-biology methods, along with way, the macrophage kills the bacterium newsletter/2017/3/feature/feature-2- X-ray crystallography, to uncover the before engulfing it. oxidative/index.htm. inner workings of cells. Their recent The scheme is a resourceful way to findings, published in the journalNature kill living things that could make a More photos at https://irp.nih.gov/cata- Communications, may help scientists person sick, but what happens when the lyst/v25i3/niehs-team-reports-how-oxi- better understand the origins of some invader is not alive? Take, for example, dative-stress-kills-cells. human diseases (Nat Commun 8:14045, the particles in cigarette smoke or smog. 2017; doi: 10.1038/ncomms14045). When these small pieces of matter enter

6 THE NIH CATALYST MAY-JUNE 2017 FEATURE

Delayed Walking Associated with Gene Anomalies in Autisms Distinct Behavioral Profiles Linked to ASD Risk Genes BY JULES ASHER, NIMH

A team of National Institute of developmental, behavioral, and genetic Mental Health (NIMH) intramural markers in ASD on March 3, 2017, and grant-supported researchers has in the American Journal of Psychiatry discovered a pattern of behavioral and (Am J Psychiatry, DOI:10.1176/appi. genetic features seen in some cases of ajp.2017.16101115). autism spectrum disorder (ASD) that Before the study, the estimated 10 to could ultimately lead to identification 15 percent of children with ASD who of subgroups and improved treatment. have noninherited, or de novo, gene-copy- Children diagnosed with ASD who number variations or suspected disrupting, had spontaneous, noninherited changes severe mutations had not been found to in autism-linked genes showed “muted” show specific patterns of ASD-related

core autism symptoms related to social symptoms or delays in developmental FLIKR GORDON, FROM ADAPTED SOURCE: behavior and language compared with milestones. The new discovery was made sex-, age-, and IQ-matched children possible through advances in genomics with ASD without known genetic technology, allowing for a large number abnormalities. A key clue was that of “high-confidence” suspect genes to children with the spontaneous glitches— be identified, as well as more rigorous abnormal numbers of copies of genes matching of children with and without or other mutations linked to functional genetic abnormalities than in previous impairments—tended to start walking studies. For example, the new study later than usual, which is not typical controlled for the potentially confounding of children with ASD. In fact, the effects of IQ , which has been previously A pattern of behavioral (such as delayed walking) and genetic odds of a child in this sample having found to be lower in children with ASD features seen in some cases of autism spectrum disorder (ASD) could ultimately lead to identification of subgroups a spontaneous abnormal gene finding with de novo mutations. and improved treatment. increased by 17 percent for each month Results showed that children with of delay in walking. de novo mutations tended to be less “Identifying individuals whose impaired on core ASD symptoms than genetic abnormalities showed subtle, yet ASD is associated with a specific type their peers with more typical ASD potentially important, differences in their of genetic abnormality may lead us to and no known genetic abnormalities. behavioral profiles when compared to distinct processes ultimately traceable to Children with de novo mutations also appropriately matched children with specific causes, which could be targeted tended to have stronger verbal, language, no such abnormalities,” said Bishop. by more personalized interventions,” and social-communication abilities, “These findings are in line with previous explained NIMH intramural researcher and clinicians involved in assessing the assertions that, as a group, de novo Audrey Thurm. “In the meantime, our children were less confident in their mutations may be best understood as results can increase awareness that among ASD diagnoses for the subgroup with conferring risk for neurodevelopmental children with an ASD diagnosis, certain de novo mutations. Yet children with problems more generally, rather than characteristics [such as] late walking are de novo mutations began walking, on ASD core symptoms specifically.” associated with genetic abnormalities.” average, at 19 months, compared with Thurm, NIMH grant–supported 13.6 months for children with typical This article first appeared on the NIMH researcher Somer Bishop of the ASD, when controlling for differences science news website at https://www.nimh. University of California at San in nonverbal IQ. nih.gov/news/science-news/2017/delayed- Francisco, and colleagues reported their “While all children in this study met walking-may-signal-spontaneous-gene- identification of an emerging cluster of diagnostic criteria for ASD, those with anomalies-in-autism.shtml.

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

Intramural Research Briefs

NHGRI: SELFIES COULD HELP DIAGNOSE A successfully identified 75 percent of primary RARE GENETIC DISEASE prostate tumors and 100 percent of meta- Taking selfies may one day help physicians static lymph nodes and bone lesions in the diagnose genetic diseases such as DiGeorge study cohort (five healthy volunteers and syndrome, which is also known as 22q11.2 13 patients with various stages of prostate deletion syndrome and is caused by a defect cancer). The probe (gallium-68–bombesin– in chromosome 22. Those with the syndrome arginylglycylaspartic acid) was well tolerated exhibit certain facial features—such as an and outperformed prostate biopsy, magnetic underdeveloped chin, low-set ears, wide- resonance imaging, and positron-emission

JIM INGLESE, NCATS set eyes, or a narrow groove in the upper tomography using fluorine-18-labeled fluo- NCATS, NHLBI: The cyclic peptide ipglycermide binds lip—and may have congenital heart disease; rodeoxyglucose in detecting prostate cancer to and blocks the activity of a cofactor-independent poor immune-system function; and delays in and metastatic lesions. Combined with other phosphoglycerate mutase (iPGM) enzyme, which is essential for glycolysis in disease-causing parasites and bacteria. growth, development, and speech. The dis- imaging tools, this new technique could pro- order is commonly underdiagnosed, espe- vide tumor-staging information and monitor- NCATS, NHLBI: INTERNATIONAL SCIENTIFIC cially in diverse populations. NHGRI scientists ing response to therapy and could serve as a TEAMS FIND POTENTIAL APPROACH used digital facial-detection analysis on 101 guide for delivering internal radiation therapy. AGAINST PARASITES photos—from consenting individuals with the Larger-scale clinical studies are needed to Parasitic nematode infections cause many syndrome—from 11 countries to determine 126 confirm the findings. (NIH authors: J. Zhang, devastating infectious diseases around the distinct geometric and textural facial features G. Niu, L. Lang, X. Yan, X. Chen, J Nucl Med world. Researchers from NCATS and NHLBI that serve as markers of the syndrome. The 58:228–234, 2017) and the University of Tokyo (Tokyo) identified facial-recognition technology accurately diag- [WRITTEN BY ALEJANDRO CHIBLY, NIDCR] the first inhibitor of an enzyme long thought nosed the syndrome 96.6 percent of the time to be a potential drug target for fighting dis- across diverse populations. The prevalence of NIAMS, NHLBI, OD: TREATING LUPUS WITH ease-causing parasites and bacteria. After smartphones in areas of the world that lack TOFACITINIB sorting through more than 1 trillion small-pro- molecular- and cytogenetic-testing facilities Tofacitinib, a drug already approved for the tein fragments (cyclic peptides), the scientists means that facial diagnostic capabilities of treatment of rheumatoid arthritis, prevented found two potential inhibitors of the enzyme. handheld devices can enhance early detec- the onset of lupus in lupus-prone mice, NIH The target enzyme—cofactor-independent tion and treatment of 22q11.2. (NIH authors: researchers found. Lupus is a chronic autoim- phosphoglycerate mutase (iPGM)—exists in P. Kruszka, Y.A. Addissie, J. Duncan, A.A. mune disease that causes widespread inflam- both parasites and bacteria and is essential for Adeyemo, and M. Muenke, Am J Med Genet mation and eventually leads to cardiovascu- glycolysis. The team collaborated with struc- 173:879–888, 2017) lar and renal damage. It is thought that high tural biologists at the University of Kansas [WRITTEN BY ALIA SAJANI, NIAID] concentrations of cytokines, especially inter- (Lawrence, Kan.) to determine the structure of ferons, are associated with the progression of the iPGM-cyclic peptide arrangement and how NIBIB: NOVEL RADIOTRACER MAY IDENTIFY the disease. Tofacitinib, which was discovered it prevented the enzyme from working prop- PROSTATE CANCER and developed at NIH, blocks the inflamma- erly. Next, the researchers will look for ways There is no single imaging technique or test tory response pathway Janus kinase–signal for cyclic peptides to enter cells. This study for diagnosing, monitoring, and staging transducers and activators of transcription. could inform developments of broad-spec- prostate cancer. NIH researchers, however, When administered to mice that had already trum antiparasitic and antibacterial agents. are taking steps to develop a single method developed lupus, tofacitinib reversed kidney (NIH authors: P. Dranchak, R. MacArthur, N.J. that, in one scan, can identify the cancer in damage, skin inflammation, and blood-vessel Baird, and J. Inglese, Nat Commun 8:14932, its early stages as well as after metastasis. abnormalities. In mice that had not yet devel- 2017; DOI:10.1038/ncomms14932) Using a novel radiotracer that recognizes oped lupus, the drug prevented onset of the [WRITTEN BY ALIA SAJANI, NIAID] two biomarkers normally found in prostate disease. Further studies are needed to deter- cancer–gastrin-releasing peptide receptor mine the efficacy and safety of using tofaci- and integrin alpha-V beta-3–the researchers tinib to control lupus symptoms in humans.

8 THE NIH CATALYST MAY-JUNE 2017 FEATURE

(NIH authors: Y. Furumoto, C.K. Smith, L. in the inner ears of newborn mice, with long- Blanco, W. Zhao, S.R. Brooks, S.G. Thacker, term benefits. The study is one of the first A. Zarzour, G. Sciumè, W.L. Tsai, A.M. Trier, L. to use gene therapy successfully to improve Nunez, L. Mast, V. Hoffmann, A.T. Remaley, J.J. hearing and restore balance in mice with a

O’Shea, M.J. Kaplan, and M. Gadina, Arthritis type of inherited deafness, called Usher syn- NIDCD Rheumatol 69:148–160, 2017) drome, also found in people. The findings [WRITTEN BY ALEJANDRO CHIBLY, NIDCR] support growing evidence that gene therapy NIDCD: Gene therapy with Whrn restores stereocilia could be an effective treatment for inherited bundles (red spikes) in the inner ear of a Whrn mutant mouse to normal length and position. Even after four types of hearing loss, deafness, and balance months, stereocilia continue to produce whirlin protein NCI: THYROID CANCER ON THE RISE disorders. The experimental gene therapy (green speckles), helping to maintain the structure and The incidence of thyroid cancer has increased function of the stereocilia and improving the mouse’s ability used in the study targets hair cells, which by 211 percent in the United States over the to hear and maintain balance. are sensory cells in the inner ear. These cells past 40 years, according to an NCI-led study. have hair-like projections called stereocilia the presence of this gluelike protein in the Researchers at NCI and Duke University Medi- that help detect and process incoming sound vagina early in pregnancy could signal early cal Center (Durham, N.C.) analyzed data from and information about movement to guide a labor). But the screenings failed to identify more than 77,000 thyroid-cancer patients person’s sense of balance. Stereocilia need most of the women who would go on to give diagnosed during 1974–2013 and from more the protein whirlin to fully grow and function birth prematurely. The researchers concluded than 2,000 thyroid-cancer deaths during properly. In one type of Usher syndrome, the that, alone or together, the methods did not 1994–2013. Although some investigators have gene that encodes whirlin, Whrn, is mutated. identify enough preterm births to support thought that the increase was due to improve- This causes the stereocilia to be abnormally using them for routine screening of first-time ments in diagnostic technology that picked up short and disorganized, making them dys- pregnancies. (NIH author: U.M. Reddy, JAMA small tumors that would have never required functional. As a result, the sensory hair cells 317:1–10, 2017) treatment, the current study challenges that cannot detect sound and information about notion. Additional research is needed, how- movement to guide the sense of balance, Read longer versions of the above briefs ever, to determine whether environmental leading to dizziness and to hearing loss or and others online at https://irp.nih.gov/ factors—such as endocrine-disrupting chemi- deafness. Read full article on NIDCD webpage catalyst/v25i3/research-briefs. The cals or changes in obesity and smoking preva- at https://www.nidcd.nih.gov/news/2017/ following are online only: lence—may be associated with the increase. gene-therapy-usher-syndrome. (NIH authors: (NIH authors: H. Lim, S.S. Devesa, D. Check, K. Isgrig, J.W. Shteamer, I.A. Belyantseva, M.C. • NHGRI: AFRICAN-SPECIFIC GENOMIC and C.M. Kitahara, JAMA 317:1338–1348, 2017) Drummond, T.S. Fitzgerald, A.J. Griffith, T.B. VARIANT ASSOCIATED WITH OBESITY Friedman, L.L. Cunningham, and W.W. Chien, NIAMS: MECHANISMS TO IMPROVE Mol Ther 25:780–791, 2017) • NICHD: EXTREME TEMPERATURES NUCLEAR REPROGRAMMING MAY INCREASE RISK FOR LOW BIRTH NIAMS researchers conducted high-through- NICHD: SCREENING TESTS FAIL TO WEIGHT put RNA sequencing of transplanted oocytes PREDICT PRETERM BIRTH IN FIRST-TIME to uncover the mechanisms that cause some PREGNANCIES • NICHD, NHGRI: ORIGINS OF BLOOD- genes to resist reactivation. The findings will Two screening methods that once seemed BRAIN BARRIER “SENTRY CELLS” help improve the success of nuclear repro- promising for predicting premature deliver- gramming. (NIH authors: S. Wang and V. Sar- ies in first-time pregnancies may not be so • NIAID, CC: NIH STUDY OF EBOLA torelli, Molec Cell 65:873–884, 2017) helpful after all. NICHD researchers screened PATIENT TRACES DISEASE PROGRES- more than 9,000 women throughout their SION AND RECOVERY NIDCD: GENE THERAPY FOR HEARING LOSS pregnancies by evaluating routine ultrasound AND DIZZINESS DISORDER examination of the uterine cervix (a short • NIAID: NIH SCIENTISTS ADVANCE Using gene therapy, scientists from NIDCD cervix early in pregnancy could be a warn- UNDERSTANDING OF HERPESVIRUS and Johns Hopkins School of Medicine (Bal- ing sign of preterm birth) and testing for fetal INFECTION timore) have corrected defective structures fibronectin (some studies have suggested that

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

The Big Read CONTINUED FROM PAGE 1

recognizes their great and terrible potential. talk, NIH Director Francis Collins asked And members of NIH’s workforce— him how he set about writing a book of the technicians, administrators, trainees, depth and scale of The Gene. professors, physicians, counselors, nurses, The most “complicated thing is and others—recognize that potential, too, not what you put in, but what you leave and were eager to discuss the ideas and out,” Mukherjee said. He was wary of concerns reflected in Mukherjee’s book. overwhelming his audience with too much For a two-month period, more than scientific information because he did not 70 individuals came together for hour- want to lose the “most important readers,” long book-discussion sessions, hosted by the non-scientists, with whom he hoped the Library. Interest was so strong that a to spark a discussion and invite into the fourth discussion group had to be opened conversations surrounding the history and to accommodate the lengthy waitlist. Unlike future of genetics. participants in some proctored events who The question is no longer “Can we?” said require prodding and pointed questions, Mukherjee. We must now ask, “Should we?” the book-club participants needed little and determine “the limits and constraints, Pulitzer-Prize-winning author Siddhartha Mukherjee visited incentive to share their thoughts on the both scientific and social…ethical that [these NIH to discuss his new book, The Gene: An Intimate History, which was featured in NIH’s inaugural Big Read event. book, its historical context, and the ethical technologies] have to be tempered with.” implications of the past few years of research. Later, he elaborated on this perspective What was remarkable was the obvious when asked what role bench scientists who scientific communication, it is not surprising time and depth of thought both scientist are developing the technologies should play that Mukherjee returned to the NIH to and nonscientists had given to many of the in these often highly charged conversations. a packed auditorium. This visit and the ethical issues raised in the final chapters of “They absolutely should” play a role, he said. successful turnout were thanks to the The Gene. As one participant pointed out, “And they definitely are.” tireless efforts of the NIH Library, who “We can’t afford to stick our heads in the From the size of the audience and the partnered with FAES, to bring literature sand and not think about these issues.” successful book clubs, it appears that the and discussion to the NIH through this Although the Big Read sought to include NIH has heard The Gene’s rallying cry Big Read program. the entire NIH in a discussion of genetics and is prepared to listen to and reflect on One of the core pillars of the Library history, medicine, and biomedical ethics, the implications that have arisen with our is to “foster collaboration and community Mukherjee had a larger goal for his book. entrance into this new age in genetics. As across NIH,” said Kathleen McGlaughlin, He stated that the book, and the coming our community has learned over the last few the librarian who oversaw the planning and documentary by Ken Burns, was meant to hundred years, the ethical implications are preparation for the entire Big Read event. reach an audience wider than “laboratories just as important as the scientific questions. The biggest hope of the project was to create and scientific institutions” and to explore The NIH Library has done an excellent a forum in which diverse members of the “the extent [to which] these technologies job of creating a space for discussion and NIH community could weigh in on The Gene [such as gene editing] will transform human community; Mukherjee provided a strong and its discussion of the latest technologies beings and human culture.” framework and context; and it is now up to in human genetics and their inevitable social, His motivation for writing The Gene us to continue the conversation. ethical, and moral implications. stemmed from three sources. The first Anyone who follows the latest in was his desire to write a prequel to his The NIH Big Read was inspired by the National biomedical research knows that the past previous book, The Emperor; the second, Endowment for the Arts Big Read program few years have seen an explosion of potential to explore the latest advances in genetics and sponsored by the NIH Library and the in terms of genome editing—led by the and medicine; and the third, to chronicle Foundation for Advanced Education in the speeding bullet that is the Crispr/Cas9 gene- his own personal familial relationship with Sciences. To watch a videocast of Mukherjee’s editing system. Mukherjee, as a physician- genetic diseases. During the question-and- April 17, 2017, presentation (NIH-only), go to scientist, has seen these breakthroughs and answer session that followed Mukherjee’s https://videocast.nih.gov/launch.asp?23226.

10 THE NIH CATALYST MAY-JUNE 2017 FEATURE ANNOUNCEMENTS: KUDOS

Microscopy as Masterpiece CONTINUED FROM PAGE 1

Stopfer, a senior investigator at the Arts and the Brain Lecture Series National Institute of Child Health and Strathmore’s “Arts and the Brain” lecture Human Development, uses simple animal series engages teachers, scholars, and art- models such as locusts to study basic ists working at the intersection of arts and questions in neuroscience. He is identifying health to present innovative, practical strat- and analyzing the properties of neurons that egies for harnessing the arts to alleviate process information about odors. He places suffering and strengthen vitality. The final an intracellular electrode into a locust neuron lecture, titled “Medical Avatar,” will take to record responses when odors are puffed place on Thursday, June 1, at 7:30 p.m., in onto the animal’s antennae. The neurons the Mansion at Strathmore. For informa- Yasmine Belkaid Elected to NAS respond with vigorous spiking when odors tion, go to https://www.strathmore.org/ are presented; when the odor changes, the education/programs-for-adults/arts-the- Congratulations to Ya s m i n e spiking patterns change, too. brain-package. Tickets cost $25 for each Belkaid who has been elected to the Stopfer had the following to say about lecture, but you can view the “Microscopy National Academy of Sciences (NAS) for how the image was produced: as Masterpiece” exhibit for free. 2017. She explores the field of immune “The image is a composite of several regulation and has defined fundamental micrographs illustrating two kinds of More images from exhibit: mechanisms that regulate tissue homeo- olfactory neurons in the locust brain. In stasis and host immune responses. She the background, in gray, is an outline of the has uncovered key roles for the commen- locust brain. Superimposed on that, in [an] sal microbiota and dietary factors in the assortment of colors, is a confocal micro- maintenance of tissue immunity and pro- scope image of the ‘mushroom bodies,’ brain tection against pathogens, demonstrating areas that process sensory stimuli and form that commensals play a major role in the memories. The image was made by injecting control of host-defense in both the skin large amounts of dye into the mushroom and the gastrointestinal tract. The NAS

bodies and then imaging them such that U. OF CALIFORNIA, SAN DIEGO announced in May that it had elected parts closer to the brain surface are more red The pinpricks of light in this starry night sky are actually 84 new members and 21 foreign associ- and parts deeper in the brain are more blue. green fluorescent protein, marking specific cells in a mouse ates in recognition of their distinguished “Finally, the image includes two retina. This detailed image was made using large-scale mosaic confocal microscopy, a technique that, like Google and continuing achievements in origi- olfactory neurons. In the intact animal, Earth, computationally stitches together many small, high- nal research. Election to the academy is each neuron was studied by placing an resolution images. considered one of the highest honors in intracellular electrode into it to record its the fields of health and medicine. Includ- responses when odors were puffed onto ing the newly elected, the total number the animal’s antennae. (Both neurons of active members is 2,290 and the total respond with vigorous spiking when odors number of foreign associates is 475. are presented; the spiking patterns change when the odor is changed.) Then, dye was injected into the neuron, and later the neuron was imaged on a confocal microscope. One Researchers in the Intramural Research HARVARD Program have won hundreds of significant cell here is colored blue and one orange. Random mixing of fluorescent dyes created this psychedelic These colors were selected artificially in slice of a mouse brain. Known as “brainbow,” the technique professional awards in the last several allows scientists to distinguish nearby cells by color and years, far too many to list comprehen- Photoshop when the composite image has helped advance the NIH Human Connectome Project.s. was assembled. Overall, the image shows sively. For highlights, go to https://irp. the locations, enormous size, and complex nih.gov/about-us/honors. branching patterns of neurons that process olfactory information.”

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

WALS Superstars NIH’s Wednesday Afternoon Lecture Series Features Nobel Laureates and Other Science Stars BY VIVIANNE CALLIER, NEI; ALEJANDRO CHIBLY, NIDCR; AND LAURA S. CARTER

The 2016–2017 NIH Director’s found that retinal ganglion axons send In 1984, Church developed the first Wednesday Afternoon Lecture Series out exploratory branches before forming direct genomic sequencing method, which (WALS) has featured a parade of science synapses with other neurons. During resulted in the first commercial genome superstars on most Wednesdays (and this process, neurons that fire together in sequence (the human pathogen Helicobactor occasionally other days), from 3:00 to 4:00 response to a common stimulus strengthen pylori). He helped initiate the Human p.m., in Masur Auditorium (Building 10). their connections and, over time, terminate Genome Project in 1984 and the Personal Each season includes some of the biggest their branches at the same location. Genome Project in 2005. He invented the names in biomedical and behavioral research. She also found that neurons firing in broadly applied concepts of molecular An added treat is the annual J. Edward Rall response to the same stimulus at slightly multiplexing and tags, homologous Cultural Lecture, which features top authors different times terminated in slightly offset recombination methods, and array DNA and other cultural icons. This season’s Rall positions in the brain. In short, neurons that synthesizers. guest was none other than world-renowned fire in sequence wire in sequence. The wiring Much of the latest progress in genomic cellist Yo-Yo Ma on December 5, 2016 (see rule ensures that information about retinal engineering has happened thanks to the the NIH Catalyst article in the January– inputs spread across the entire target area research in Church’s lab. Undoubtedly, one February 2017 issue). in the brain. of his more influential contributions has WALS speakers are nominated by the been the development of the CRISPR- NIH community. To check out the rest of Read more in the April 7, 2017, issue of the NIH Cas9 gene-editing system, which allows the season, which ends on June 28, go to Record. To see a videocast of the Cline’s WALS for site-specific, programmable DNA https://oir.nih.gov/wals/current-lecture- lecture, “Building Circuits to Process Visual cleavage in single cells or whole organisms. season. The 2017–2018 season begins in Information,” go to https://videocast.nih.gov/ Currently, the system is being used for September. Here’s a taste of what 2016–2017 launch.asp?21087. a vast array of biomedical and research season had to offer. applications, from controlling transcription of specific genes to alleviating genetic GEORGE CHURCH: THE FUTURE OF GENETIC disorders in animals. HOLLIS CLINE: BUILDING A BRAIN THAT SEES CODES Church has also exploited the BY VIVIANNE CALLIER, NEI BY ALEJANDRO CHIBLY, NIDCR advantages of this system to trace the cause and effect of point mutations in patient- New research is revealing how On February 8, geneticist George derived and genetically engineered induced visual activity guides the development Church (Harvard Medical School, pluripotent stem cells, to provide insight of brain circuits that support vision. Boston) delivered the annual Marshall into the pathophysiology underlying the The findings may help Nirenberg Lecture, which recognizes cardiomyopathy of Barth syndrome (Nat researchers understand 1968 Nobel Laureate Nirenberg for Med 20:616–623, 2014). the origins of diseases his work deciphering the genetic code. Furthering the advancement of medicine such as amblyopia, Church himself was with the CRISPR method is one of Church’s explained Hollis Cline, a major contributor goals. He believes, for example, that we president of the Society to one of Science’s Top can overcome the shortage of organs for Neuroscience and 10 Breakthroughs of for transplantation by using CRISPR professor at the Scripps Research Institute 2013—the CRISPR- gene editing to inactivate endogenous (San Diego, California), at the January Cas method of gene retroviruses that can create problems in 18 WALS. Amblyopia is when the vision editing. He is also pig-to-human xenotransplants. Beyond in one of the eyes is reduced because the widely recognized for his innovative medical applications, Church also discussed brain is favoring the other eye. Cline contributions to genomic science and the potential (and concerns) of altering wild imaged developing tadpoles, whose brains his many pioneering contributions to populations to address ecological problems. are clearly visible through their skin, and chemistry and biomedicine.

12 THE NIH CATALYST MAY-JUNE 2017 FEATURE

One shortcoming of the CRISPR- LINDA BUCK: UNRAVELING SMELL Südhof is interested in how synapses Cas9 technology is what Church referred Not only does WALS have named form and function in the developing and to during his presentation as the double- lectures in honor of Nobel laureates, adult brains. His work focuses on the role of strand-break dilemma: “When you make but also some of the lecturers are Nobel synaptic cell-adhesion molecules in estab - a double-strand break, it’s a race between laureates themselves. lishing synapses and shaping their proper - the cell fixing it and getting your donor Linda Buck (Fred ties, on pre- and postsynaptic mechanisms DNA to fix it how you want,” he explained. Hutchinson Cancer of membrane traffic, and on impairments To overcome this efficiency limitation, Research Center, in synapse formation and synaptic function Church’s lab is working on CRISPR-Cas9 Seattle), who won the in neuropsychiatric and neurodegenerative alternatives that would allow gene editing 2004 Nobel Prize in disorders. He shared the 2013 Nobel Prize while avoiding double-strand breaks. With Physiology or Medicine in Physiology or Medicine with James E. this new approach, Church and his team (with Richard Axel) for her discoveries of Rothman and Randy W. Schekman “for have successfully performed the largest and odorant receptors and the organization of their discoveries of machinery regulating most radical genome engineering to date, the olfactory system, presented the annual vesicle traffic, a major transport system in altering the genetic code in Escherichia coli. Margaret Pittman Lecture on March 29. our cells.” The end result is an organism that depends Pittman was the first woman to be a on nonstandard amino acids to survive laboratory chief at NIH (1957–1971) and is If you can’t make the talk in person, you can and thus is easily biocontainable, and it recognized for her work on an improved and watch a videocast at http://videocast.nih.gov. possesses a unique synthetic genetic code standardized pertussis (whooping cough) that prevents horizontal gene transfer and vaccine; the isolation of the influenza strain confers resistance to almost any virus. This responsible for most childhood meningitis; ATUL GAWANDE (TUESDAY, JUNE 13, 2017) work provides a foothold for developing the identification of the cause of epidemic Surgeon, writer, and public health safer genetically modified organisms conjunctivitis; and her key observations researcher Atul Gawande (Harvard (Nature 518:55–60, 2015; Science 342:361– that led to the development of a Salmonella Medical School) will give a talk on 363, 2013). vaccine. Tuesday, June 13. He practices general The CRISPR-Cas9 gene-editing In her lecture, Buck talked about her and endocrine surgery at Brigham and technique has opened the door for pioneering work that has shed light on how Women’s Hospital (Boston). He is a developing therapies that remained thousands of odor molecules are detected professor in the Department of Health somewhat unthinkable until recently. For in the nose and translated by the brain into Policy and Management at the Harvard instance, the possibility of engineering perceptions and instinctive behaviors. T.H. Chan School of Public Health and one’s own genome has attracted fans since the Samuel O. Thier Professor of Surgery the advent of CRISPR-Cas9—so much so A videocast of her lecture, “Unravelling Smell,” at Harvard Medical School (Boston). that do-it-yourself gene-therapy kits are will be available soon at https://videocast.nih. Gawande has been a staff writer for The available in the market for reversing aging. gov/PastEvents.asp (search “past lectures” for New Yorker magazine since 1998 and has Church cautions that there hasn’t been March 29, 2017). written four New York Times bestsellers: extensive testing of these approaches but Complications, Better, The Checklist Manifesto, agrees that veterinary preclinical trials, and most recently, Being Mortal: Medicine which his group is working on, place THOMAS CHRISTIAN SÜDHOF: SYNAPSE and What Matters in the End. He is the human studies in the foreseeable future. FORMATION IN THE BRAIN (COMING IN 2018) winner of two National Magazine Awards, Another Nobel laureate, Thomas Academy Health’s Impact Award for highest To watch a videocast of George Church’s Christian Südhof (Stanford School of research impact on health care, a MacArthur WALS lecture, “The Future of Genetic Codes Medicine, Stanford, Fellowship, and the Lewis Thomas Award and BRAIN Codes,” go to https://videocast. California), was originally for writing about science. nih.gov/launch.asp?21127. scheduled to give a WALS lecture this year, but will The Gwande lecture will be videocast to NIH coming on Wednesday, only at http://videocast.nih.gov. January 31, 2018, instead.

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

Going the Distance Teresa Przytycka: Driven by Curiosity and Big Dreams BY KATHRYN MCKAY, NLM

If you ask computational biologist So she applied to a Ph.D. program in Teresa Przytycka where she’s from, and computer science at the same university. she’s likely to quip, “Do you mean geo- Again, Przytycka felt fortunate—UBC graphically or scientifically?” accepted her. Plus, she was accepted with- Both answers cover long distances for out having to take an English test. her. Her journey, which began in Poland “[A] Slovak professor recognized the many years ago, brought her to NIH where names of some of the mathematicians who she’s a senior investigator in the National taught me [from] the so-called ‘Polish School Library of Medicine’s National Center for of Mathematics,’ [which] had international Biotechnology Information (NCBI). recognition,” she explained. “UBC had faith in me.” The geographical journey It was only after arriving in Vancouver Przytycka was born and raised in Myszków, that Przytycka had to take English exams. Poland, a small city with three factories Even though she hadn’t taken English in surrounded by a rural area. Although her school, her knowledge of German and a parents were educated, they “came from friendship with an American journalist a village where…people typically ended proved to be helpful. their education at basic reading and writing “The journalist wanted to learn about skills,” she said. “In fact, since they grew life under communism, so we spent lots of up during the war, a good chunk of my time together,” she said. “I was a member of parents’ schooling was within the Polish ‘Solidarity’—an underground anticommunist underground education system—very brave movement. Sometimes, I helped translate but not very rigorous.” texts from underground newspapers for her.” Despite growing up under unassuming Przytycka planned to get her Ph.D. and circumstances, Przytycka considers herself return to the University of Warsaw. But fortunate. She was lucky enough to have a by the time she had earned her degree in BRANSON BILL group of curious friends in school. “I think computer science in 1990, she also had two we inspired each other in dreaming big,” sons—a toddler and an infant. She decided she said. Her curiosity and big dreams have not to go back to Poland after all. She knew stayed with her. she wouldn’t be able to work because there She studied at the University of Warsaw was a “lack of support for children this She remembers receiving an invitation to a (Warsaw, Poland), earning a master’s degree young and social pressure to be a stay-at- faculty barbecue that read, “Wives are wel- in mathematics with a concentration in com- home mom [and] very few day-care centers,” come.” She joked, “Can Jozef come?” But puter science. After graduating, she stayed she said. most of the time she says she didn’t think at the university, working as a research and With her two boys in tow, she chased very much about being the only woman (and teaching assistant in the Department of down opportunities in the departments of later one of two) in the department. Mathematics, Mechanics, and Informatics. computer science at University of Southern It was there she met her husband, Jozef, who Denmark at Odense (Odense, Denmark) The beginnings of a new direction had a Ph.D. in mathematics from Columbia and the University of California, Riverside. In the mid-1990s, she told her husband, University (New York). Shortly after they Her husband followed when he could, but “Next time you find a position, I’ll follow married, Jozef was offered a postdoctoral often she was on her own with the children. you.” Unbeknownst to her at the time, she position at the University of British Colum- She was also many times the only female would be doing more than following her bia (UBC) in Vancouver, Canada. member of the computer-science faculty. husband. She would be forging a new career.

14 THE NIH CATALYST MAY-JUNE 2017 PROFILE

When her husband secured a position more] mathematical, more quantitative, and, at George Washington University (Wash- from my perspective, far more exciting,” she ington, D.C.), Przytycka, as promised, fol- said. “It’s fair to say that I was amongst the lowed him, starting with a visiting position first group of computer scientists that made at the University of Maryland (College Park, their way to biology.” Maryland). Through the years, she has built her team At the same time, while her research was of men and women thoughtfully—albeit

still focused on the theory of algorithms, unconventionally. JAN NIBIB HOINKA, she began working on questions that were “Often people come to my group with- motivated by biology. out any knowledge of biology,” Przytycka “There were some nice mathematical said. “You are well-served if people in your questions that arise in the context of evo- group are strong in computer science, and lution and other interesting, biologically since this is the field where I’m coming Schematic of one selection cycle of HT-SELEX (high-throughput motivated mathematical problems. How from, it’s easier for me to work with people systematic evolution of ligands by exponential enrichment), would you construct evolutionary trees? who think mathematically. I am able to which is used to identify aptamers. How to measure an agreement between see where their strengths are and can help two evolutionary trees constructed with them navigate biology, so they can direct “This research is an excellent example different methods?” she explained. “Those their talents toward solving biological of how the benefits of ‘big data’ critically are very mathematical questions, and while questions.” depend upon the existence of algorithms they don’t require biological understanding, that are capable of transforming such data they started my interest in biology.” Three areas into information,” she said. Her interest was piqued even more when Przytycka’s team works in three basic areas: she learned from the Notices of American cancer and diseases, gene regulation, and Driven by curiosity Mathematical Society that the Department algorithms for the efficient utilization of Whatever she’s working on, Przytycka of Energy and the Sloan Foundation had large datasets. appreciates the opportunities at NIH. announced a new fellowship in computa- In the context of disease studies, her “Researchwise, I’m working on a large tional biology. Before she could apply, she group develops computational methods spectrum of problems. I think that working needed to find a mentor in biology. With advancing systems-level understanding of for NIH particularly helps me do that,” she the help of a computer science colleague, cancer, the emergence of complex pheno- explained. “I am surrounded by experts she found one: George Rose, a professor types, and the detection of causal genetic working on diverse biological inquiries,” she at Johns Hopkins University (Baltimore) mutations and their interactions. said. “Exposure to this variety of biological and a well-known biophysicist working on As for gene regulation, she collaborates questions and the realization that they can be protein folding. with Brian Oliver’s group (National Insti- helped with novel computational methods With this fellowship in hand, she crossed tute of Diabetes and Digestive Diseases) to makes it is hard to resist and not give them the line from working on computer-science work on fruit flies and is developing methods a try.” questions that are motivated by biology to for constructing condition-specific regulatory For this mathematician computer biological questions that require computer networks. She also work with David Levens scientist who works in biology, curiosity is science. (National Cancer Institute), on non-B DNA a large part of what drives her. And when structures and their role in gene regulation, that curiosity can be helped with an elegant The road to NCBI mutagenesis, and diseases. computational algorithm, this is the best A few years later, in 2003, she was hired as The third area relates to analysis of big combination. a principal investigator at NCBI. Not only data. For example, they developed novel was it a dream position scientifically, but clustering and motif-finding algorithms. hers and Jozef’s “two-body” problem—two Her team developed a software tool This article was adapted from one that researchers trying to find jobs in the same called AptaTRACE that could help drug appeared in NLM In Focus: https:// geographical area—was finally solved. developers and scientists identify molecules infocus.nlm.nih.gov/2017/02/06/ She was officially working toward a that bind with high precision to targets teresa-przytycka-goes-the-distance. career in biology. “Biology has [become of interest.

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

Recently Tenured

TERRI S. ARMSTRONG, NCI-CCR ANIL K. CHATURVEDI, NCI-DCEG PETER DOBBS CROMPTON, NIAID THEO HELLER, NIDDK ZHIYONG LU, NCBI

TERRI S. ARMSTRONG, PH.D., NCI-CCR system, the treatments for patients with (such as electronic data capture and use of Senior Investigator, Neuro-Oncology Branch, malignant brain and spinal cord tumors in-home and wearable technology). Center for Cancer Research, National Cancer rarely result in a cure. In my research In a second project, done jointly with Institute program, we are developing measures to NOB clinical investigators, we will be Education: University of Akron, Akron, Ohio accurately assess symptoms of cancers of incorporating COAs into brain-tumor (B.S.N.); Ohio State University, Columbus, the central nervous system (CNS) and clinical trials. We will gauge the utility Ohio (M.S. in oncology; post-master’s nurse the impact of the disease and therapy on of including COAs in early-phase and practitioner); University of Texas Health Sci- patient outcomes. precision-medicine clinical trials; evalu- ence Center, Houston (Ph.D. in nursing) Our efforts have included the develop- ate innovative approaches to assessment; Before coming to NIH: Professor and John S. ment, psychometric evaluation, and assess- and apply these findings to improve the Dunn Distinguished Professor at the Univer- ment of the utility of instruments as well understanding of the natural history of sity of Texas Health Science Center–School as the use of patient-reported outcomes common and rare CNS malignancies as of Nursing; adjunct professor, Department (PRO) in multicenter clinical trials. We well as the survivorship and palliative-care of Neuro-Oncology, University of Texas MD are also exploring the clinical and genomic needs. Anderson Cancer Center (Houston) predictors of risk of symptoms and toxic- In a third project, we are identifying Came to NIH: In 2016 ity and investigating the underlying patho- clinical and genomic predictors of treat- Selected professional activities: Associate physiology to develop approaches to care ment-related toxicities in CNS cancers, editor of Neuro-Oncology and of Neuro- and symptom management. Our work tumor-associated symptoms, and com- Oncology Practice; vice president, Society has focused on myelotoxicity and vascular plications. We will also study alterations of Neuro-Oncology; board of directors of toxicity associated with chemotherapeutic in circadian rhythms in fatigue and sleep the Collaborative Ependymoma Research agents as well as fatigue and hypersomnia and evaluate select medical and neuro- Foundation; quality-of-life representative (excessive daytime sleepiness) associated logic complications such as seizures and to the Neuro-Oncology Committee of NRG with cranial radiation. thrombosis. and Brain Tumor Committee of Alliance We are focusing on four areas. In one Our fourth project involves patient Oncology project, we are developing the Neuro- education, outreach, and outcomes. Outside interests: Adopting and caring for Oncology Branch (NOB) Patient Out- Much of the patient-outcomes data will rescue dogs; cooking; traveling comes Program, which will combine be generated by patients’ participation Website: https://irp.nih.gov/pi/ research and clinical care for patients with in the NOB natural-history study. We terri-armstrong CNS cancers. We will be interrogating will have an unprecedented opportunity disease and therapeutic correlates of select to integrate clinical-outcomes data with Research interests: Although there have PROs and other clinical-outcome assess- COAs and genomics, but we need to been many advances in neurosurgery, radi- ments (COAs) measures as well as develop- establish the applicability to the general ation oncology, and imaging of the nervous ing innovative approaches to assessment CNS-cancer patient population. Therefore,

16 THE NIH CATALYST MAY-JUNE 2017 COLLEAGUES

an educational and outreach effort, par- Research interests: I study the molecular I am collaborating with NCI-DCEG ticularly for the rare CNS cancers, will epidemiology of head and neck cancers colleague Hormuzd Katki to develop, vali- be critical for validating the data and dis- and lung cancers. date, and apply lung-cancer risk-stratifica- seminating information about the disease Head and neck cancers, which are the tion tools. In 2011, the landmark National trajectory. We will incorporate patient edu- eighth most common cancer worldwide, Lung Screening Trial (NLST) showed a cation into the research component and occur in the oral cavity (lips and mouth), 20 percent decrease in mortality from lung provide patients and their caregivers with oropharynx (base of tongue back through cancer in the low-dose CT group as com- important information about the illness, tonsil area), other parts of the pharynx pared with the group that received stan- treatment, and possible clinical outcomes. (part of throat leading from the oral and dard chest X-rays. On average, over three In addition, we will test novel educational nasal cavities to the esophagus and larynx), rounds of screening exams, 24 percent of tools, a task made difficult because of the and the larynx (voice box). Risk factors the CT scans were positive compared with neurologic complications from CNS cancer include tobacco and alcohol use; poor oral 6.9 percent of the X-rays. Most positive or its treatment. hygiene; low fruit and vegetable consump- screens led to additional tests. Based on Our findings will be shared with other tion; and human papillomavirus (HPV) these results, LDCT screening is currently groups that deal with brain tumors, other infection. HPV has been found to be an recommended for the highest-risk smokers neurologic disorders, or cancer. etiologic agent for oropharyngeal cancers, who meet the NLST entry criteria. but it rarely causes oral cavity and larynx I am researching the potential utility cancers. I am using population-based stud- of lung-cancer risk-prediction tools to ANIL K. CHATURVEDI, PH.D., NCI-DCEG ies to investigate the epidemiology, the improve the population-level effectiveness Senior Investigator, Infections and Immu- natural history, and the unique anatomic, of LDCT screening. Additionally, I study noepidemiology Branch, Division of Cancer histopathologic, and molecular charac- minimally invasive lung-cancer biomarkers Epidemiology and Genetics, National Cancer teristics of HPV-positive oropharyngeal for improved risk stratification. Institute cancers. Education: Andhra N.G.Ranga Agricultural Cancers of the oral cavity are easy to University, School of Veterinary Medicine, detect visually, making them ideal can- PETER DOBBS CROMPTON, M.D., M.P.H., NIAID Hyderabad, India (B.S. in veterinary didates for early detection and second- Senior Investigator, Laboratory of Immuno- sciences and animal husbandry); Tulane ary prevention. But we don’t understand genetics, and Chief, Malaria Infection Biology University, New Orleans (M.P.H. and Ph.D. in enough to be able to develop guidelines and Immunity Section, National Institute of epidemiology) for screening, treatment, or follow-up Allergy and Infectious Diseases Training: Postdoctoral training at NCI’s of patients with oral-cancer precur- Education: Boston University, Boston (B.A. Infections and Immunoepidemiology sor lesions. I am using a combination in biochemistry and molecular biology); Branch; became a research fellow in 2007 of retrospective and prospective cohort Johns Hopkins School of Medicine, Baltimore Came to NIH: In 2005 for training; was studies to address key questions about to (M.D.); Johns Hopkins School Public Health, appointed as a tenure-track investigator in the natural history and molecular predic- Baltimore (M.P.H.) 2009 tors of oral-cancer precursor lesions and Training: Clinical fellow and resident in Selected professional activities: Member, how they progress to cancer. internal medicine at Massachusetts General Oral Cancer Screening Guidelines Panel, Lung cancer, the leading cause of death Hospital, Harvard University (Boston); clini- American Dental Association; external from cancer in the United States, is usu- cal and research fellow in infectious diseases advisor, Scientific Advisory Board, Catalan ally caused by cigarette smoking (80 to at NIAID; diploma in tropical medicine and Institute of Oncology/International Agency 90 percent of cases). But there are other hygiene, London School of Hygiene and for Research on Cancer HPV Information risk factors, too, such as chronic inflam- Tropical Medicine (London) Center (Barcelona, Spain) mation. I am studying the role of chronic Came to NIH: In 2004 for training; in 2010 Outside interests: Cooking; playing and inflammation in lung cancer by measur- became a tenure-track investigator and chief watching tennis ing circulating immune and inflammation of NIAID’s Malaria Infection Biology and Website: https://irp.nih.gov/pi/ marker concentrations in case-control stud- Immunity Unit anil-chaturvedi ies nested within large prospective cohorts.

CONTINUED ON PAGE 18

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

Recently Tenured CONTINUED FROM PAGE 17

Selected professional activities: Board malaria-induced inflammation is regulated, Selected professional activities: Several of consulting editors, Journal of Clinical and gained insights into fundamental aspects positions in the American Association for Investigation; guest editor, Proceedings of malaria epidemiology, including the rela- the Study of Liver Diseases: chair, Technol- of the National Academy of Sciences and tionship between chronic asymptomatic P. ogy and Social Media Committee; elected PLoS Pathogens; co-chair, Malaria Gordon falciparum infection and malaria risk. vice-chairman, Portal Hypertension Special Research Conference 2017 and 2019; Our studies in Mali are made possible Interest Group; Hepatitis C Virus Guidance member, American Society for Clinical through a collaboration with an experi- Panel; and member of the Ethics Committee Investigation enced team of clinicians and scientists at Website: https://irp.nih.gov/pi/theo-heller Outside interests: Enjoys spending time the Malaria Research and Training Center at with his wife and three daughters—biking, the University of Bamako (Bamako, Mali). Research interests: Liver disease presents hiking, cooking, singing, and playing musical Through this collaboration we also facilitate a unique confluence of many disciplines instruments the expansion of research capacity in Mali in both the basic science and the clini- Website: https://irp.nih.gov/pi/ by training scientists, improving laboratory cal realms. There are many unanswered peter-crompton infrastructure, and enhancing information questions in basic hepatic biology and the technology. Our field studies in Mali are development of liver disease. Our labora- Research interests: Malaria caused by supported by the NIAID International Cen- tory is interested in testing hypotheses Plasmodium falciparum remains a major cause ters for Excellence in Research program. We in clinical situations that can be trans- of morbidity and mortality worldwide. A hope that our work not only contributes to a lated into laboratory projects, which in limited understanding of the interaction better understanding of malaria immunity turn might lead to fundamental biologic between malaria and the human immune but also provides insights into the mecha- insights and improved disease manage- system hinders the development of malaria nisms at play in human immune responses ment. Clinical observations can some- vaccines. Clinical immunity to malaria to infectious diseases more generally. times be best explained at the bench, can be acquired but only after years of and human-disease investigation is in repeated infections, and immunity wanes many ways better than a model—it is a rapidly without ongoing malaria exposure. THEO HELLER, M.D., NIDDK direct study of authentic biology. Human The mechanisms and targets of protective Senior Investigator and Chief, Translational disease is a window into biology, and by malaria immunity and the factors underlying Hepatology Section, Liver Diseases Branch, studying diseases, researchers may be able its inefficient acquisition remain unclear. In National Institute of Diabetes and Digestive to extrapolate from some rare, derived the Malaria Infection Biology and Immunity and Kidney Diseases concepts to a far broader understanding Section, we aim to accelerate malaria-vaccine Education: University of Cape Town, Cape of biologic principles. development and gain fundamental insights Town, South Africa (B.Sc. in experimental We focus on the connections between into human immunology by addressing these biology and zoology; B.Sc. in immunology); the innate immune system and liver- knowledge gaps. University of the Witwatersrand Medical related damage and repair. Our clinical We apply advances in basic immunol- School, Johannesburg, South Africa (M.D.) focus is on non-cirrhotic portal hyperten- ogy and functional genomics to clinical Training: Residency in internal medicine, sion. We also study people with chronic data and biospecimens obtained through Georgetown University Hospital (Wash- granulomatous disease, sickle-cell dis- intensive longitudinal cohort studies con- ington, D.C.); research associate, Hepatitis ease, Turner syndrome, sporadic nodu- ducted at our field sites in Mali and else- Viruses Section, Laboratory of Infectious lar regenerative hyperplasia, hepatitis D, where. Recently, we have determined key Diseases, National Institute of Allergy and acute hepatitis C, and congenital hepatic features of the specificity, function, and Infectious Diseases; fellow in gastroenter- fibrosis. kinetics of the antibody response to malaria, ology, University of Maryland School of Liver disease disproportionately affects identified mechanisms by which B-cell and Medicine (Baltimore) people during their most productive work- T-follicular-helper-cell responses contribute Came to NIH: In 1999 as a clinical associate ing years. We hope that our research will to the inefficient acquisition of protective in NIDDK; became a staff clinician in 2003; result in more effective treatments and antibodies, defined mechanisms by which became a tenure-track investigator in 2011 fewer people dying of the disease.

18 THE NIH CATALYST MAY-JUNE 2017 NIH ABBREVIATIONS COLLEAGUES 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 ZHIYONG LU, PH.D., NCBI filtering or predicting flu trends). In Health Research, NICHD FAES: Foundation for Advanced Education Senior Investigator, National Center for the health-care industry, text mining in the Sciences Biotechnology Information, National is essential in helping to find important FARE: Fellows Award for Research Excellence Library of Medicine information that’s buried within tens of Education: Nanjing University, Nanjing, FelCom: Fellows Committee millions of biomedical articles. FDA: Food and Drug Administration China (B.S. in computer science); Uni- My research group is developing FNL: Frederick National Laboratory versity of Alberta, Edmonton, Alberta, new computational methods and soft- IRP: Intramural Research Program Canada (M.S. in computer science); Uni- HHS: U.S. Department of Health ware tools to analyze and make sense and Human Services versity of Colorado School of Medicine, of free text data in scholarly publica- NCATS: National Center for Advancing Translational Sciences Aurora, Colorado (Ph.D. in bioinformatics) tions and other biomedical texts such as Came to NIH: In 2007 as a staff scientist; NCBI: National Center for Biotechnology elesctronic medical records. We apply Information became an associate investigator in 2009; text-mining research to improve bio- NCCIH: National Center for became a Stadtman investigator in 2011 Complementary and Integrative Health medical literature search; assist in the NCI: National Cancer Institute Selected professional activities: manual curation of biological databases; NEI: National Eye Institute Associate editor, BMC Bioinformatics and predict new uses of existing drugs. NHGRI: National Human Genome and Journal of Healthcare Informatics Research Institute Our text-mining software tools and web NHLBI: National Heart, Lung, Research; Editorial board member, services, such as PubTator, have been and Blood Institute Database; Steering committee member, widely used (over 100 million requests NIA: National Institute on Aging BioCreative; PI, PubMed Labs NIAAA: National Institute on Alcohol since 2015) by scientists from around Abuse and Alcoholism Outside interests: Playing with his three the world and has also been integrated NIAID: National Institute of Allergy young children; swimming and Infectious Diseases into PubMed, PubChem, and many NIAMS: National Institute of Arthritis Website: https://irp.nih.gov/pi/ other NCBI web resources. and Musculoskeletal and Skin Diseases zhiyong-lu I also co-organize international NIBIB: National Institute of Biomedical Imaging and Bioengineering scientific conferences and community- NICHD: Eunice Kennedy Shriver Research interests: I am directing wide challenges such as BioCreative, National Institute of Child Health and Human Development text-mining research and lead the new the longest-running international event NIDA: National Institute on Drug Abuse overall efforts to improve and rebuild for evaluating text-mining and infor- NIDCD: National Institute on Deafness PubMed. (Our current development is mation-extraction systems applied to and Other Communication Disorders NIDCR: National Institute of Dental an innovative system called PubMed the biomedical domain. and Craniofacial Research Labs in which we are experimenting NIDDK: National Institute of Diabetes and Digestive and Kidney Diseases with new ways to improve search quality NIEHS: National Institute of and usability for biomedical literature.) Environmental Health Sciences Text mining involves going through NIGMS: National Institute of General Medical Sciences digitized and unstructured text to find NIMH: National Institute of Mental Health useful, high-quality information. Text If you have been recently tenured, the NIH NIMHD: National Institute on Minority Health and Health Disparities analysis includes retrieving relevant Catalyst will be contacting you soon about NINDS: National Institute of documents; identifying named entities including you on these pages. It’s a great Neurological Disorders and Stroke NINR: National Institute of Nursing Research (such as gene and disease names); and way for your colleagues to get to know National Library of Medicine extracting relationships between entities NLM: about you and your work. OD: Office of the Director and other natural language processing OITE: Office of Intramural Training tasks. The technology is now applied to and Education Office of Intramural Research a broad range of government, research, OIR: ORS: Office of Research Services and business and marketing needs, and ORWH: Office of Research on Women’s Health it is used in a wide variety of real-world OTT: Office of Technology Transfer applications (such as automatic spam

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If you have a photo or More Cajal on Campus other graphic that reflects an aspect of life at NIH This drawing of an (including laboratory life) or olfactory bulb is one of seven a quotation or confession that newly arrived original drawings scientists might appreciate and by Spanish scientist Santiago that would be fit to print in Ramón y Cajal, who shared the the space to the right, why not 1906 Nobel Prize in Physiology send it via e-mail: catalyst@ or Medicine in recognition of nih.gov; fax: 301-402-4303; his work on the structure of the or mail: The NIH Catalyst, nervous system. This drawing Building 1, Room 333. and six others are on loan from Also, we welcome “letters to the Cajal Institute (Madrid) and the editor” for publication and on display on display on the first SANTIAGO Y RAMÓN CAJAL your reactions to anything on floor of the Porter Neuroscience the Catalyst pages. Research Center (Building 35) until the end of 2017. Two previous installations were on display for six READ MORE ARTICLES, AND months. Cajal, known as the father EXPANDED VERSIONS OF THE of modern neuroscience, was a ONES IN THIS ISSUE, ONLINE AT prolific medical artist and produced hundreds of drawings depicting the organization of nerve cells in the brain. Read more online at https://irp.nih.gov/catalyst/v25i3 https://irp.nih.gov/catalyst/v25i3/back-page.

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