Colleagues: Recently Tenured

PHILIP E. BOURNE, PH.D., NLM-NCBI

Senior Investigator, National Center for Biotechnology Information, National Library of Medicine

Phil Bourne

Education: Flinders University, Adelaide, South Australia (B.Sc. in chemistry; Ph.D. in chemistry)
Training: Postdoctoral training in biochemistry, University of Sheffield (Sheffield, U.K.)
Before coming to NIH: Professor and associate vice chancellor for Innovation and Industry Alliances, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California–San Diego (La Jolla, Calif.)
Came to NIH: In 2014
Selected professional activities: NIH associate director for Data Science, Office of the Director; founding editor-in-chief, PLOS Computational Biology; editor, Database
Outside interests: Motorcycling; flying planes; hiking

Research interests: My research over the past 35 years has been in structural bioinformatics, systems pharmacology, immunology, cell signaling, scholarly communication, and evolution. Currently, I am focusing on three areas: protein fold space and its implications; systems pharmacology; and scholarly communication.
My lab staff and I have been designing and extending algorithms to address the question of the evolutionary and functional implications of protein fold space (the tiny fraction of three-dimensional space occupied by protein structures in nature as opposed to what is theoretically possible). We are building a three-dimension-based connectivity network of all known proteins from which we can overlay functional and other properties to address such questions as do gaps in fold space serve a purpose; what are the functional implications of symmetry; and can evolutionary events be traced back to protein structure?

We are using systems-pharmacology approaches to understand how medicines work on different systems of the body. The paradigm of one-drug-one-receptor to treat one disease has been replaced by the notion that a single small-molecule drug binds to multiple targets. We have tried to model this new notion using highly simplified systems in ways that are both static and dynamic. As a result we have been able to predict the side effects of drugs, suggest repurposing options for approved drugs, and suggest chemical modifications to make drugs more effective. At the heart of our approach is an understanding of the structural basis of the drug-target interaction, its implications for affected networks of interactions, and the changes to the dynamics of a living system. We use structural bioinformatics algorithms we have developed, network tools developed by others, and flux-balance analysis models developed by a collaborator.

In our scholarly communication work, we have been developing tools and using the Internet to disseminate and comprehend science. Prior work involved being an advocate for new modes of scholarly communication and developing tools deployed through the Protein Data Bank and elsewhere. Going forward we hope to explore and understand data-usage patterns; build citation networks for data with the goal of highlighting that data availability is underappreciated; and explore the impact of data on innovation by association with the patent database and beyond.


GEORGE F. KOOB, PH.D., NIDA

Senior Investigator, Section Chief, Neurobiology of Addiction Section, National Institute on Drug Abuse

George Koob

Education: Pennsylvania State University, State College, Pa. (B.S. in zoology); Johns Hopkins University, Baltimore (Ph.D. in behavioral physiology)
Training: Postdoctoral training in experimental psychology, University of Cambridge (Cambridge, U.K.) and the Medical Research Council Neurochemical Pharmacology Unit (Cambridge)
Before coming to NIH: Professor and chair, Committee on the Neurobiology of Addictive Disorders, Scripps Research Institute (La Jolla, Calif.)
Came to NIH: In 2014
Selected professional activities: Director, National Institute on Alcohol Abuse and Alcoholism; neuropsychopharmacologist with a focus on understanding the neurocircuitry of alcohol and drug addiction; scientific writer; author of a definitive text on the neurobiology of addiction
Outside interests: Gardening (particularly the cultivation of fruit trees); traveling; enjoying art; cooking
Web site (intramural): http://irp.drugabuse.gov/Koob.php

Research interests: My research at Scripps, before coming to NIH, and at NIH focuses on understanding the neurobiology of drug and alcohol addiction. In my earlier work, I contributed to the understanding of the neurocircuitry associated with the reinforcing effects of drugs of abuse. More recently I studied the neuroadaptation of the reward circuits and the recruitment of the brain stress systems associated with the transition to dependence. My lab studies how cellular and molecular changes produce alterations in neurocircuits to convey negative emotional states that contribute to the motivation to seek drugs and alcohol.

We are also exploring the relationship between pain and emotional systems in the context of the same neurocircuitry. The neurocircuitry under study is in the basal forebrain and involves the extended amygdala—the central nucleus of the amygdala, bed nucleus of the stria terminalis, and elements of the ventral striatum including the shell and core of the nucleus accumbens. We are identifying the molecular elements that load such circuits and neurotransmitter system function, the cellular interactions between brain stress systems, and the role that outputs to the brain stem (for example, the hypothalamus) play in the expression of negative emotional states.
Our research will provide key information not only about the neurobiology of addiction, pain, and stress but also about the neurobiology of motivational and emotional systems in general. Ultimately, by understanding the underlying brain changes that foster the compulsive use of drugs and alcohol, we hope to accelerate the development of new, targeted treatments that will help individuals who suffer with addiction.


XIAOLING LI, PH.D., NIEHS

Senior Investigator, Metabolism, Genes, and Environment Group, Signal Transduction Laboratory, National Institute of Environmental Health Sciences

Xiaoling Li

Education: Peking University, Beijing (B.S. in biochemistry); Chinese Academy of Sciences, Beijing (M.S. in molecular biology); Johns Hopkins University School of Medicine, Baltimore (Ph.D. in biological chemistry)
Training: Postdoctoral research fellow at the Massachusetts Institute of Technology (Cambridge, Mass.)
Came to NIH: In 2007
Selected professional activities: Editorial board of the Journal of Metabolomics and Metabolites and the Journal of Geriatric Cardiology; Phi Beta Kappa; American Society for Biochemistry and Molecular Biology; American Society for Microbiology
Outside Interests: Skiing; hiking; enjoying music and art with her kids
Web site: http://irp.nih.gov/pi/xiaoling-li

Research interests: My group’s long-term goals are to understand the molecular-signaling pathways that coordinate the gene-environment interactions in homeostasis and to investigate how the dysregulation of this coordination contributes to disease and aging. We study a family of proteins called sirtuins, which are key cellular metabolic sensors that regulate metabolism, stress response, and possibly longevity. Understanding how sirtuins are regulated, as well as how they modulate energy metabolism and stress responses, may offer new therapeutic strategies against human metabolic diseases.

Our efforts have focused on the role of SIRT1, the most conserved mammalian sirtuin, in energy metabolism, inflammation, and stress response, as well as the molecular mechanism underlying environmental regulation of SIRT1 activity. Using a combination of biochemical, molecular, cellular, and genetic approaches, we uncovered several novel targets of SIRT1 in several cell types and tissues. We have demonstrated that SIRT1 is not only a pivotal regulator of metabolism and inflammation in response to nutrient signals and environmental stress, but is also critical in the regulation of embryonic stem-cell pluripotency, differentiation, and animal development. In addition, we elucidated a novel mechanism that activates SIRT1 in response to environmental stress.


JON R. LORSCH, PH.D., NICHD

Senior Investigator and Section Head, Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Jon Lorsch

Education: Swarthmore College, Swarthmore, Pa. (B.A. in chemistry); Harvard University, Cambridge, Mass. (Ph.D. in biochemistry)
Training: Fellowship in biochemistry at Stanford University (Stanford, Calif.)
Before coming to NIH: Professor, Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine (Baltimore)
Came to NIH: In 2013
Selected professional activities: Director, National Institute of General Medical Sciences
Outside interests: Cooking; eating; gardening; biking
Web site: http://annualreport.nichd.nih.gov/lorsch.html

Research interests: My lab studies the translation of genetic information into proteins. Proteins are the body’s workhorses and are necessary for almost every activity, from muscle movement to brain function, digestion, and oxygen transport in the blood. If translation is not properly controlled, cells can grow unchecked and form cancerous tumors. Translation is also a security vulnerability: Viruses infect our cells by hijacking the machinery responsible for translation, forcing it to assemble viral proteins instead of cellular ones. We are studying how translation begins. To make a new protein based on the information encoded in a messenger RNA (mRNA), the cell assembles a ribosomal complex that reads the mRNA and synthesizes the corresponding protein. We are investigating how this apparatus is assembled and how the process is regulated.

To do this, we use the yeast Saccharomyces cerevisiae as a model system and employ a range of approaches—from genetics to biochemistry to structural biology—in collaboration with other NICHD labs and several research groups around the world.

For example, in collaboration with Alan Hinnebusch’s lab (NICHD), we probed the functions of conserved identity element bases in the initiator transfer RNA (tRNA). Our data indicate that each region of the tRNA plays important roles in start-codon recognition. The start codon is the first codon of an mRNA translated by a ribosome. In collaboration with Hinnebusch’s and Venki Ramakrishnan’s (Medical Research Council, U.K.) labs, we also determined the three-dimensional structure of a ribosomal complex initiating on an mRNA using cryoelectron microscopy.


HANNAH A. VALANTINE, M.D., M.R.C.P., F.A.C.C., NHLBI

Senior Investigator, Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute

Hannahh Valantine

Education: Chelsea College of Science and Technology, University of London, London (B.Sc. in biochemistry); St. George’s Hospital Medical School, University of London (M.B.B.S.); Royal College of Physicians, London (M.R.C.P.); University of London (Doctorate of Medicine; M.D.)
Training: Residencies in general medicine and cardiology at hospitals in London; cardiology clinical training at the Royal Postgraduate Medical School, Hammersmith Hospital (London); postdoctoral research fellowship in cardiac transplantation at Stanford University School of Medicine (Stanford, Calif.)
Before coming to NIH: Senior associate dean for Diversity and Leadership, director of Heart Transplantation Research, and professor of medicine at Stanford University School of Medicine
Came to NIH: In 2014
Selected professional activities: Chief officer for Scientific Workforce Diversity, Office of the Director; member of the National Research Council’s committee on the Science of Team Science; member of the NIH Featured Panel: Science of Team Science, Diversity of Teams; past president of the American Heart Association’s Western States Affiliate Board
Outside interests: Enjoys spending time with her husband, who has a background in information technology, and their two daughters; traveling; sailing; fine dining; and exercising

Website: http://irp.nih.gov/pi/hannah-valantine

Research interests: Since the beginning of my cardiology research career, I have been interested in the causes of heart-transplant rejection. Why do transplants fail? What injury does the failure cause? How can we improve patient outcomes? Most recently, I have been investigating noninvasive methods to monitor heart- and lung-transplant rejection.

This work hinges on the notion that an organ transplant is akin to a genome transplant. My lab showed previously that the detection of increasing amounts of donor-derived circulating cell-free DNA in a transplant recipient’s blood—taking a “liquid biopsy”—can indicate damage of the transplanted organ and ultimately organ failure.

My lab and I are now assessing the broader clinical utility of this method in graft-rejection surveillance: My lab has established a prospective, multicenter extramural-intramural research consortium—the Genome Research Alliance for Transplantation—that leverages the intellectual capacity of extramural clinical centers with the NIH Intramural Research Program’s cutting-edge genomic approaches. The consortium includes five local transplant centers in the

Washington, D.C., metropolitan area, all of which have pre-transplant and post-transplant clinics.
Future projects in my lab will explore the utility of cell-free donor DNA detection for identifying infection and degree of immunosuppression. Currently, these two outcomes are difficult to distinguish in a clinical setting but require distinct treatment paradigms. Measurement of circulating cell-free donor-derived DNA may also open a new window to investigating early immunologic markers associated with antibody-mediated rejection and acute cellular rejection.

To read more about Hannah Valantine’s work, go to http://irp.nih.gov/catalyst/v23i4/the-organ-prophet