Colleagues: Recently Tenured

LORENZO LEGGIO, M.D., PH.D., M.SC., NIAAA and NIDA

Senior Investigator and Chief, Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN), a joint National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA) laboratory; Associate Director for Clinical Research, Medication Development Program, NIDA

Education: Catholic University of Rome, Rome (M.D.; Ph.D. in physiopathology of nutrition and metabolism); Department of Clinical Physiopathology, University of Florence, Florence, Italy (M.Sc.)

Training: Residency in internal medicine, Agostino Gemelli University Polyclinic, Catholic University of Rome, Rome; postdoctoral fellowship in psychiatry and human behavior, Brown University (Providence, Rhode Island)

Before coming to NIH: Assistant professor, Warren Alpert Medical School and Public Health Program, Brown University

Came to NIH: In 2012 as a tenure-track clinical investigator

Selected professional activities: Professor (adjunct), Department of Behavioral and Social Sciences, Brown University; member, American College of Neuropsychopharmacology; member of several editorial boards of scientific journals; member of several advisory boards

Outside interests: Listening to music; watching movies; going to the opera

Website: https://irp.nih.gov/pi/lorenzo-leggio

Research interests: My laboratory conducts clinical and translational inpatient and outpatient studies to identify possible novel medications for addiction. My group uses a combination of state-of-the-art, innovative biobehavioral and pharmacological procedures performed under well-controlled laboratory conditions. Brain-imaging techniques, such as functional magnetic-resonance imaging, are also used. We are particularly interested in the role of the gut-liver-brain axis in alcohol- and drug-seeking behaviors.

Specifically, we are currently investigating the potential role of feeding-related pathways—such as those for the hormones ghrelin, leptin, oxytocin, and glucagon-like peptide 1—as possible new neuropharmacological targets for the treatment of alcohol- and substance-use disorders. We are also investigating other neuroendocrine pathways such as the aldosterone-mineralocorticoid receptor pathway.

We have recently expanded our research to look at the role of the gut microbiome in heavy drinkers of alcohol. Our special emphasis is on the relationships between alcohol-related seeking behaviors and the microbiome-gut-brain axis. Future research includes work on the effects of bariatric surgery on alcohol-related seeking behaviors.

Our preclinical work—in collaboration with other laboratories—and human studies in our lab aim to shed light on the possible role of these pathways in alcohol- and substance-use disorders.

FRANK MALDARELLI, M.D., PH.D., NCI-CCR

Senior Investigator and Head, Clinical Retrovirology Section, HIV Drug Resistance Program Host-Virus Interaction Branch, Center for Cancer Research, National Cancer Institute

Education: Johns Hopkins University, Baltimore (B.A. in biology); City University of New York, New York (Ph.D. in biomedical sciences); Mount Sinai School of Medicine, New York (M.D.)

Training: Residency in internal medicine, The Presbyterian Hospital (New York); medical staff fellow and senior staff fellow, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases (NIAID)

Came to NIH: In 1988 for training; became a clinical associate in NIAID in 1996; became clinical associate in NCI in 1998; became staff physician in 1999; in 2012, became head of Clinical Retrovirology Section, HIV Dynamics and Replication Program

Selected professional activities: Attending physician in NIAID and in the HIV Service in the NIH Clinical Center’s Critical Care Medicine Department

Website: https://irp.nih.gov/pi/frank-maldarelli

Research interests: HIV infection can be controlled, but not cured, by current combination antiretroviral therapy (cART); a large reservoir of HIV-infected cells that persists during cART prevents HIV eradication and contributes to long-term morbidity and mortality. My laboratory is conducting clinical studies at the NIH Clinical Center to investigate mechanisms underlying HIV persistence during cART. We are also studying the long-term effects of HIV persistence including the emergence of resistance to HIV drugs in individuals undergoing cART and the spread of HIV within individuals in populations.

One of the most critical challenges limiting the development of curative strategies for HIV is the lack of understanding of the precise mechanisms underlying HIV persistence during cART. We and others have demonstrated that HIV-infected cells may persist for many years during cART and undergo clonal expansion. In new studies at the NIH Clinical Center, we are investigating the origin and persistence of long-lived clonal populations of infected cells. In most cases, we have found that clonal expansion is not driven by the integrated provirus but is the result of normal T-cell behavior. We are determining the distribution of these infected cell clones within T-cell subsets and in anatomic compartments within infected individuals. In clinical studies, we are investigating whether clinical events, such as co-infections, drive clonal expansion and HIV persistence. In new studies, we will be determining the roles of these clonal populations in reactivation of HIV after antiretroviral therapy is interrupted.

In a second research project, we are investigating the genetic structure of HIV populations in infected individuals. The goal of this study is to understand the nature of the forces (mutation, selection, drift, and recombination) that mold the genetic diversity of virus populations before and after cART is introduced. We are determining the roles of HIV population size, genetic drift, selection, and recombination in shaping HIV populations and in the emergence of drug resistance during cART.

We have also adapted these genetic approaches to investigate the spread of HIV, including drug-resistant variants, in populations. In studies with investigators in NIAID and NCI, as well as with collaborators at Georgetown University and George Washington University (both in Washington, D.C.), we are characterizing the origin and spread of the HIV epidemic in Washington, D.C., which has the highest prevalence of HIV in the United States. Our studies will be an important part of the effort to control and eliminate this epidemic.

ALEKSANDRA URSZULA NITA-LAZAR, PH.D., NIAID

Senior Investigator and Chief, Cellular Networks Proteomics Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases

Education: University of Warsaw, Warsaw, Poland (M.S. in molecular biology); University of Basel, Basel, Switzerland (Ph.D. in biochemistry)

Training: Postdoctoral fellow, Stony Brook University (Stony Brook, New York); postdoctoral associate, Massachusetts Institute of Technology (Cambridge, Massachusetts)

Came to NIH: In 2009

Selected professional activities: Executive editor, Journal of Proteomics; member of Human Proteome Organization Council

Outside interests: Taking every opportunity to actively spend time outside with her son and her husband; reading; knitting; running and coaching running at the county running club; doing and teaching yoga.

Website: https://irp.nih.gov/pi/aleksandra-nita-lazar

Research interests: My research focuses on understanding the changes that occur in the cell proteome in response to exogenous factors such as pathogen-derived molecules, cytokines, and chemokines. These factors alter the differentiation state of cells in the immune system or characterize specific disease states. My group is especially interested in large-scale absolute-quantitative measurements of immune-cell signaling cascade components and in the characterization of post-translational modification (PTM) dynamics on a global scale. We use the resulting large datasets to create predictive models of molecular interactions by use of the Simmune software generated by NIAID’s Computational Biology Section. The predictions of these models will in turn be employed to elucidate biological responses to stimuli at multiple scales of biological organization including the cell, tissue, and, eventually, the whole organism.

With state-of-the art equipment and technologies available in our laboratory and at NIH, we use mass-spectrometry-based technology together with other proteomic and biochemical methods.

In one of our projects, we are investigating the protein modifications involved in cell signaling. Because dynamic PTMs such as phosphorylation, ubiquitination, or glycosylation are essential for the regulation of cell signaling, it is crucial to quantitatively map the PTMs of proteins involved in signaling cascades. Examples of our interests include toll-like receptor signaling in macrophages.

In another project, we are interested in the absolute quantification of protein expression and protein-protein interactions. We have established a methodology for analyzing the lipid-induced signaling pathways—in which sphingosine-1-phosphate (S1P) receptor 1 and S1P2 receptor play a role in monocyte and macrophage cell lineage–derived osteoclast precursors—that control cell mobilization at bone surfaces. We are currently working on the absolute quantification of molecules in the macrophages exposed to different toll-like receptor ligands, which play a key role in the innate immune system.

LORNA ROLE, PH.D., NINDS

Senior Investigator, Circuits, Synapses and Molecular Signaling Section; Scientific Director, National Institute of Neurological Disorders and Stroke

Education: Harvard University, Cambridge, Massachusetts (A.B. in applied mathematics); Harvard Medical School, Boston (Ph.D. in physiology)

Training: Postdoctoral training with Gerald D. Fischbach (who later became the director of NINDS and served from 1998 to 2001) at Harvard Medical School and at Washington University School of Medicine (St. Louis)

Before coming to NIH: 2008–2018: State University of New York (SUNY) Distinguished Professor and Chair, Department of Neurobiology and Behavior, College of Arts and Sciences and the Renaissance School of Medicine, SUNY Stony Brook (Stony Brook, New York); co-director, Neurosciences Institute and co-director of SUNY Stony Brook’s Thomas Hartmann Center for Parkinson Research; 1985–2008: professor of cell biology, Department of Neurobiology and Behavior, Columbia University College of Physicians and Surgeons (New York)

Came to NIH: In February 2019

Selected professional activities: Elected Fellow of the American Association for the Advancement of Science; elected Fellow in the American College of Neuropsychopharmacology; reviewing editor for several scientific journals

Outside interests: Spending time with family; looking at and doing art (painting and sculpture); studying the history of architecture and traveling to experience it; enjoying jazz and classical music

Website: TBA

Research interests: My research focuses on the brain’s cholinergic system over the lifespan. Cholinergic signaling—which is essential for attention, cognitive processing, and memory—is compromised in neurological disorders including Alzheimer disease and Parkinson disease. The lab has focused primarily on physiological approaches to cholinergic circuits and neural-systems analysis in genetically modified mice. Recently, we have expanded our research to include human studies of mild cognitive impairment. In this work, we are using a novel positron-emission tomography tracer of cholinergic neurons in the brain.

We are using new molecular genetic approaches to dissect the role of cholinergic modulation in the encoding of high-salience memories. Detecting saliency (the quality of something standing out or being noticeable) facilitates learning and survival by enabling organisms to focus their perceptual and cognitive resources on the most pertinent subset of the available sensory data.

We are also developing high-volume imaging and computational approaches for mapping cholinergic projections, and we have been collaborating on studies of new imaging probes for the assessment of cholinergic-terminal integrity in dementia.

For more about Lorna Role, who was recently appointed scientific director of NINDS, go to https://irp.nih.govcatalyst/v27i3/ninds-welcomes-lorna-role-as-new-scientific-director.

EDWINA H. YEUNG, PH.D., NICHD

Senior Investigator, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Education: Johns Hopkins University, Baltimore (B.A. in natural sciences area and public health studies); Johns Hopkins Bloomberg School of Public Health, Baltimore (Sc.M. in clinical epidemiology; Ph.D. in cardiovascular disease epidemiology)

Training: Postdoctoral fellow in epidemiology, NICHD

Came to NIH: In 2008 for training; became tenure-track investigator in 2011

Selected professional activities: Editorial board member, Fertility & Sterility

Outside interests: Cooking; fishkeeping (an aquarium hobby)

Website: https://irp.nih.gov/pi/edwina-yeung

Research interests: My research aims to understand the developmental origins of health and disease (DOHaD), a theory that hypothesizes that a fetus’s adaptive responses to a broad range of environmental cues influence its long-term health. Specifically, I am examining the effects of infertility treatment, obesity during pregnancy, and their related comorbidities on the “programming” of different health outcomes including early childhood development and cardiometabolic risk.

Most recently, a few studies have examined the cardiometabolic health of children conceived by infertility treatment. There is some indication that vascular alterations may have occurred in the children who were conceived by such treatments. The rationale remains unclear, but scientists hypothesize that the supraphysiological exposure to hormonal treatment may be a potential mechanism. As such, it is important to investigate not only children conceived by assisted reproductive technologies but also children conceived by ovulation-induction methods. To this end, I have overseen the completion of the first phase of the Upstate KIDS Study and continue to lead its prospective follow-up. The Upstate KIDS Study is a large exposure-matched cohort from New York state that was formed to determine whether children conceived by infertility treatments differ from their peers in growth and development.

There is increasing recognition that parental obesity may influence not only the metabolic health but also the cognitive development of the child. We hypothesize that exposure to increased inflammation in utero may be the mechanism, but causal evidence is lacking. My research has also examined whether epigenetic differences (specifically DNA methylation) exist and act as mediators of later health conditions. However, because DOHaD research has traditionally focused on mothers, I am also leading a new initiative to look at the father’s contribution. In an upcoming pregnancy cohort, we will examine the effect of cardiometabolic health status of both parents on the neonatal health of their offspring.