Colleagues: Recently Tenured

LAUFEY THORA AMUNDADOTTIR, PH.D., NCI-DCEG

Senior Investigator, Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute

LAUFEY THORA AMUNDADOTTIR

Education: University of Iceland, Reykjavik, Iceland (B.S. in biology; fourth-year degree in genetics); Georgetown University, Washington, D.C. (Ph.D. in cell biology)

Training: Postdoctoral fellow in the laboratory of Philip Leder, Department of Genetics, Harvard Medical School (Boston)

Before coming to NIH: Division head, Department of Cancer Genetics, deCODE Genetics (Reykjavik; 1998–2006)

Came to NIH: In 2007 as a senior scientist in NCI-DCEG’s Cancer Genomics Research Laboratory; became tenure-track investigator in the Laboratory of Translational Genomics in 2008

Selected professional activities: Co-leader for PanScan and the Pancreatic Cancer Cohort Consortium; Co-chair, Pancreatic Cancer Interest Group (PCIG), NCI; Steering Committee member, Center of Excellence in Integrative Cancer Biology and Genomics, NCI

Outside interests: Traveling with her family; hiking; camping; reading

Website: https://irp.nih.gov/pi/laufey-amundadottir

Research interests: Pancreatic cancer is one of the leading causes of cancer mortality in the United States. It is often diagnosed at an advanced stage, contributing to a dismal survival rate. My research focuses on the interface between gene-mapping and the function of inherited pancreatic-cancer risk variants.

I co-lead gene-mapping approaches within the Pancreatic Cancer Cohort Consortium, which is in the framework of the NCI Cohort Consortium. One of the approaches I co-lead is PanScan, a genome-wide association study (GWAS) of pancreatic cancer. We collaborate with national and international consortiums to identify genetic factors that contribute to the risk of pancreatic cancer. Our GWAS includes close to 12,000 cases and 17,000 control subjects from more than 30 cohort and case-control studies from the United States, Europe, and Asia. Our GWAS has led to the discovery of 23 common susceptibility signals for pancreatic cancer. Further GWAS phases, as well as studies aimed at uncovering less common and rare pancreatic-cancer risk variants, are underway.

My laboratory is also working toward explaining the underlying biology of pancreatic-cancer susceptibility variants. Our research involves fine-mapping of risk loci identified in PanScan, collaborative gene-mapping efforts, and multiple genomic and wet-lab approaches. Some of those approaches are targeted at investigating specific risk loci whereas others are tailored to the analysis of multiple risk loci simultaneously. Our aim is to identify functional variants and their target genes at each locus and uncover the mechanisms by which they influence pancreatic-cancer risk.


SONJA BERNDT, PHARM.D., PH.D., NCI-DCEG

Senior Investigator, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute

SONJA BERNDT

Education: Dartmouth College, Hanover, N.H. (A.B. in English literature); University of Michigan, Ann Arbor, Mich. (Pharm.D.); Johns Hopkins University, Baltimore (Ph.D. in epidemiology)

Training: Cancer Research Training Award (CRTA) fellow, Occupational and Environmental Epidemiology Branch, NCI-DCEG; research fellow, Occupational and Environmental Epidemiology Branch, NCI-DCEG

Came to NIH: In 2003 as a CRTA fellow in NCI while still in Ph.D. program; became research fellow in 2007, tenure-track investigator in 2009, and senior investigator in 2017

Selected professional activities: Editorial boards of Environmental and Molecular Mutagenesis and of Cancer, Epidemiology, Biomarkers, and Prevention

Outside interests: Spending time with her children; horseback riding; hiking; reading

Website: https://irp.nih.gov/pi/sonja-berndt

Research interests: As a genetic and molecular epidemiologist, I have primarily focused on using cutting-edge statistical methods to elucidate the genetic underpinnings of cancer and related conditions. I am also exploring other molecular biomarkers to further understand the complex etiology of cancer. My training in genetics and epidemiology, combined with my knowledge of statistics and pharmacology, has allowed me to integrate and merge knowledge from different disciplines to pursue a broad range of important scientific projects.

From my early days as a predoctoral fellow at NCI, I have been interested in discovering the genetic determinants of prostate-cancer risk. I began my research at NCI by conducting candidate-gene studies but quickly realized the need for a more general approach as well as large sample sizes. I have co-led and collaborated on multiple genome-wide association studies (GWAS) collaborations, which have identified more than 100 genetic loci associated with cancer risk. Together these genetic variants explain approximately 33 percent of the familial risk in populations of European ancestry. But many questions remain, such as how these genetic variants interact with environmental exposures and how they may be used to inform and predict cancer risk in the context of screening. I am exploring these and other questions in my research.

As part of the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, which is an international consortium of investigators interested in anthropometric traits (such as body-mass index), I am studying genetic variants related to obesity and height. I co-led several large-scale meta-analysis GWAS identifying multiple loci for height and body-mass index and elucidating some of the underlying biological pathways behind these quantitative traits. There is still much that can be learned, however, from studying these traits. I am currently exploring the contribution of height, which may serve as a marker of increased exposure to growth hormones; other factors that stimulate cell growth and proliferation; and the role of adiposity in cancer risk.

In my non-Hodgkin lymphoma (NHL) research, I am trying to identify genetic loci associated with different NHL subtypes, such as follicular lymphoma and chronic lymphocytic leukemia (CLL). I co-lead a large GWAS for NHL, which currently includes more than 9,000 cases from 22 studies of people of European ancestry. This effort has led to the discovery of 27 new genetic variants associated with specific subtypes of NHL, more than doubling the number of identified loci for NHL, and the identification of a key role for apoptosis in CLL susceptibility.

Although some regions of the genome were shown to harbor variants associated with susceptibility to more than one NHL subtype, most discovered loci were subtype-specific, suggesting substantial etiologic heterogeneity among subtypes. I am currently expanding this study and hope to further elucidate the genetic architecture of NHL.


JOSÉ FARALDO-GÓMEZ, PH.D., NHLBI

Senior Investigator, Theoretical Molecular Biophysics Section, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute

JOSÉ FARALDO-GÓMEZ

Education: Universidad Autónoma de Madrid, Madrid, Spain (B.Sc. in physics); University of Oxford, Oxford, England (Ph.D. in computational molecular biophysics)

Training: Postdoctoral training in Department of Physiology and Biophysics at Weill Cornell Medical College (New York); postdoctoral training in Department of Biochemistry and Molecular Biology at University of Chicago (Chicago)

Before coming to NIH: Max-Planck Research Group Leader at the Max Planck Institute of Biophysics (Frankfurt, Germany)

Came to NIH: In 2013 as tenure-track principal investigator in NHLBI

Selected professional activities: Associate editor, The Journal of General Physiology; editorial board member, Biophysical Journal

Outside interests: Sailing; playing tennis

Website: https://irp.nih.gov/pi/jose-faraldo-gomez

Research interests: The aim of my research program is to help elucidate the structural mechanisms of biomedically important molecular systems associated with cellular membranes. We are particularly interested in systems that are involved in transmembrane transport, signaling, and energy conversion.

Membrane proteins mediate many essential processes in living cells, such as the import and metabolism of nutrients and the transmission of chemical signals between and within cells. A wide range of human health disorders, from heart disease to neurodegeneration, are therefore associated with the malfunction of membrane-associated systems. Membrane-transport proteins are also crucial for the survival of multidrug-resistant pathogenic bacteria and cancer cells and are promising pharmaceutical targets. I believe that a detailed understanding of the molecular mechanisms of these fascinating systems will eventually facilitate the design of more effective pharmacological approaches.

Our investigations rely primarily on computationally intensive, physics-based molecular simulations and related theoretical methods. This approach enables us to formulate novel mechanistic hypotheses and interpretations of existing empirical data, which in turn guide the design of new experimental work. Our theoretical studies are often carried out in synergy with experimental collaborators, both at NIH and elsewhere, particularly in the areas of structural biology, biochemistry, and molecular biophysics.

On the methodological front, we are actively involved in the development and implementation of novel approaches to extract reliable thermodynamic and mechanistic information from molecular simulations.


SAMER HATTAR, PH.D., NIMH

Chief and Senior Investigator, Section on Light and Circadian Rhythms, National Institute of Mental Health

SAMER HATTAR

Education: Yarmouk University, Irbid, Jordan (B.S. in biology, minor in chemistry); American University of Beirut, Beirut, Lebanon (M.S. in biochemistry); University of Houston, Houston (Ph.D. in biochemistry)

Training: Postdoctoral fellow, Department of Neuroscience, The Johns Hopkins University (JHU)–School of Medicine (Baltimore)

Before coming to NIH: Associate professor, Department of Biology and joint appointment: Department of Neuroscience, JHU, and JHU–School of Medicine

Came to NIH: In 2017

Selected professional activities: Elected vice chair for the 2019 Gordon Conference on Chronobiology and chair for 2021; editorial board of the Journal of Biological Rhythms; elected secretary for the Society of Research on Biological Rhythms (2014–2016)

Outside interests: Watching and playing soccer; traveling to our treasured national parks; enjoying good food and company

Website: https://www.nimh.nih.gov/labs-at-nimh/principal-investigators/samer-hatt...

Research interests: For many years, it was assumed that rods and cones were the only photoreceptors capable of detecting light in the mammalian retina. However, research from several laboratories uncovered a third type of photoreceptor cell, called intrinsically photosensitive retinal ganglion cells (ipRGCs). They express their own photopigment called melanopsin. My lab’s main goals are to understand how ipRGCs detect light and send light information to the brain to regulate physiology and behavior.

We have shown that ipRGCs target many of the brain’s visual centers, including the circadian pacemaker and the area responsible for pupil constriction, and are critical for the influence of light on circadian rhythms, sleep, mood, and pupil constriction. Recently we found that ipRGCs are more abundant than previously appreciated and that there are at least five different subtypes. Some of these subtypes target regions of the brain involved in image formation and allow mice that lack rod and cone function to have rudimentary pattern vision. In addition, we have found that ipRGCs also mediate the negative effects of light on mood and learning and enhance the ability to detect contrast in an image.

Many questions still remain about the function of these cells and the circuits that are critical for ipRGC-mediated behaviors. We are continuing our explorations using a variety of techniques including mouse genetics, anatomy, in vivo calcium imaging, viral-circuit tracing, and animal behavior.


SANDRA LYNN WOLIN, M.D., PH.D., NCI-CCR

Senior Investigator and Chief, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute

SANDRA LYNN WOLIN

Education: Princeton University, Princeton, N.J. (A.B. in biochemical sciences); Yale School of Medicine, New Haven, Conn. (M.D.); Yale University, New Haven, Conn. (Ph.D. in molecular biophysics and biochemistry)

Training: Postdoctoral training at the University of California, San Francisco (San Francisco)

Before coming to NIH: Director, Yale Center for RNA Science and Medicine; Professor of Cell Biology and Molecular Biophysics and Biochemistry, Yale School of Medicine

Came to NIH: In 2017

Selected professional activities: Fellow of the American Association for the Advancement of Science and of the American Academy of Microbiology; editorial board of the RNA Journal; associate editor, Molecular Biology of the Cell

Outside interests: Hiking with her husband; gardening; enjoying her artist son’s work

Website: https://irp.nih.gov/pi/sandra-wolin

Research interests: Most transcripts in cells do not encode proteins; instead, most RNAs are noncoding. My laboratory studies how noncoding RNAs function, how cells recognize and degrade defective RNAs, and how the failure to degrade these RNAs affects cell function and contributes to human disease.

One pathway that we study involves noncoding RNA–protein complexes known as Ro60 ribonucleoproteins (RNPs). These RNPs were discovered because they are clinically important targets of the immune system in people with the disease systemic lupus erythematosus. RNP’s major protein component, the ring-shaped Ro60 autoantigen, is present in most animal cells, some archaea, and about five percent of bacteria. In all studied organisms, Ro60 binds noncoding RNAs called Y RNAs. By studying Ro60 RNPs in bacteria, we discovered that the Ro60 protein and Y RNA are complexed with a ring-shaped nuclease, forming a double-ringed machine specialized for structured RNA degradation. Interestingly, Ro60 contributes to the survival of mammalian cells and some bacteria in the presence of stresses, such as ultraviolet light, that damage nucleic acids. We are defining this new RNA-degradation machine in mechanistic detail and uncovering additional roles for Ro60 and Y RNAs in both mammalian cells and bacteria.

We recently discovered a new RNA-surveillance pathway in mammalian cells. In this work, we collaborated with researchers at the University of Michigan (Ann Arbor, Mich.) to study how retroviruses such as the human immunodeficiency virus type 1 assemble in the cytoplasm of infected cells. It has long been known that retroviruses package their own genomes into virions as well as encapsidate specific cellular noncoding RNAs. We discovered that retroviruses package these host-cell RNAs from a previously unknown pathway in which defective and unneeded newly made RNAs are exported to the cytoplasm for degradation. We are characterizing this new RNA-surveillance pathway in molecular detail and are also determining how the packaged RNAs contribute to retrovirus replication.


JINFANG (JEFF) ZHU, PH.D., NIAID

Senior Investigator, Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases

JINFANG (JEFF) ZHU

Education: Nankai University, Tianjin, China (B.S. in biochemistry); Shanghai Institute of Biochemistry (now Shanghai Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences, Shanghai, China (Ph.D. in biochemistry and molecular biology)

Training: Visiting fellow, Laboratory of Immunology, NIAID

Came to NIH: In 1998 as visiting fellow in NIAID; in 2002 became staff scientist; in 2011, became a Stadtman Investigator in the Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, NIAID

Selected professional activities: Review editor, Frontiers in Immunology; editorial board, Journal of Interferon and Cytokine Research; editorial board, Cellular and Molecular Immunology

Outside interests: Listening to music; playing pingpong; swimming; hiking

Website: https://irp.nih.gov/pi/jinfang-zhu

Research interests: My lab is investigating the heterogeneity and plasticity of immune cells and their functions during normal and pathological immune responses at the cellular and molecular levels. In particular, we are focusing on transcriptional regulation in CD4 T-helper (Th) cells and innate lymphoid cells (ILCs) as well as the relationship between these adaptive and innate lymphocyte subsets.

CD4 T cells—including regulatory T cells (Tregs) and effector Th cells—and recently identified ILCs play important roles in host defense and inflammation. Both CD4 T cells and ILCs can be classified into distinct lineages based on their functions and the expression of lineage-specific genes, including those that encode effector cytokines, cell-surface markers, and key transcription factors. Appropriate differentiation and activation of these lymphocytes are essential for mounting different types of immune responses to various microorganisms. Inappropriate responses to pathogens may lead to chronic infection and/or tissue damage to the host.

Similarly, unnecessary activation of ILCs and Th cells by harmless environmental or host-derived factors can cause autoimmune diseases or allergic inflammatory diseases.

The differentiation and development of Th cell and ILC subsets are tightly regulated by specific transcription-factor networks. Some of the master regulators of Th and ILC lineages have been identified, but emerging data suggest that there are many more critical transcription factors in the regulatory network that are critical for T-cell and ILC fate determination and function.

In our research, we are identifying lineage-specific genes in Th and ILC subsets, some of which may serve as biomarkers and/or targets for treating specific human diseases. To understand the mechanisms of transcriptional regulation of lineage-specific genes, we also use chromatin immunoprecipitation followed by high-throughput sequencing to assess genome-wide epigenetic modifications in different cell types, including cells from genetically modified mice, and to map DNA-binding sites for key transcription factors.

A complete understanding of how transcription-factor complexes are regulated and how they precisely control Th and ILC cell heterogeneity, plasticity, and stability has great implications for designing strategies to treat a broad range of immune-related diseases, including chronic bacterial and viral infections such as human immunodeficiency virus infection, autoimmune diseases, allergic diseases, and cancers.