Colleagues: Recently Tenured
DEBORAH CITRIN, M.D., NCI-CCR
Senior Investigator, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute
Education: North Carolina State University, Raleigh, N.C. (B.S. in biology); Duke University School of Medicine, Durham, N.C. (M.D.)
Training: Residency in general internal medicine, Washington Hospital Center (Washington, D.C.); residency in radiation oncology, National Cancer Institute and the National Cancer Consortium
Came to NIH: In 2001 for residency training; became a staff clinician (2005–2007), an associate clinical investigator (2006–2007), and an investigator (2007)
Selected professional activities: Co-chair of the Biology Track Abstract Review Committee and member of the Scientific Program Committee, American Society for Therapeutic Radiology and Oncology
Outside interests: Entertaining her three children
Research interests: My clinical and laboratory work focuses on improving radiation treatments to eradicate cancer cells while minimizing damage to normal tissue. A portion of my work involves understanding mechanisms of radiation resistance in tumor tissue. A small subset of tumors will never be cured by radiation, and we can’t always predict which patients have these resistant tumors. By understanding these mechanisms, we can better determine which patients will need more-aggressive treatment and target the specific pathways that lead to radiation resistance. In addition, by understanding the pathways active in recurrent tumors, we can better develop such regimens as salvage therapy for patients with tumors that recur after irradiation.
On the other hand, aggressive radiation treatments can cause injury to the normal tissue that surrounds the tumor. Radiation therapy has changed drastically over the past 30 years as newer techniques allow improved sparing of normal tissue adjacent to or surrounding the tumor. Serious side effects do continue to occur in some patients, however. Understanding the causes of this injury and ways to prevent or treat it is another major area of my laboratory research and my clinical trials. In the laboratory, we are trying to develop therapies that exploit the differences between tumor and normal tissues in an effort to sensitize the tumor to irradiation while preventing radiation injury. Ultimately, this selective radiation will improve tumor cure while minimizing late injury from treatment. I am involved in the clinical care of patients with genitourinary cancers (prostate and bladder), gastrointestinal cancers, and a variety of other solid and liquid malignancies.
TIM F. GRETEN, M.D., NCI-CCR
Senior Investigator and Head, Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute–Center for Cancer Research
Education: University of Kiel, in Kiel, Germany (M.D.)
Training: Internship in internal medicine, Ludwig Maximilian University of Munich (Munich); 3-year postdoctoral fellowship in tumor immunology at Johns Hopkins University (Baltimore); training in internal medicine, medical oncology, and gastroenterology at Hannover Medical School (Hannover, Germany)
Before coming to NIH: Associate professor in the Department of Gastroenterology, Hepatology, and Endocrinology at Hannover Medical School
Came to NIH: In 2010
Selected professional activities: Editor of United European Gastroenterology Journal; associate editor of Clinical Cancer Research and Journal of Hepatology
Outside interests: Spending quality time with his family
Research interests: My research is focused on the liver, cancer, and immunology. I have projects in basic tumor immunology and translational research studies in hepatocellular carcinoma (HCC) and liver metastasis. In addition, I am doing clinical trials in different gastrointestinal malignancies, including HCC. My lab and I are trying to better understand tumor immune interactions and immunological responses to anticancer treatment. I am convinced that a combined effort using different antitumor approaches will result in the best possible outcome for our patients. Based on this idea, I take studies from bedside to bench and back.
Currently we are studying different aspects of the local tumor microenvironment. These include studies on the microbiome, metabolic changes, and innate immune cells. I am trying to translate our findings obtained in the laboratory into the clinic. In addition, we are studying how ablative therapies including radiofrequency ablation, cryoablation, transarterial chemoembolization, and radiation can be combined with immune-based treatments in patients with hepatobiliary tumors and patients with colon cancer and liver metastasis.
RAJA JOTHI, Ph.D., NIEHS
Senior Investigator, Systems Biology Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences
Education: University of Madras, Chennai, India (B.E. in computer science and engineering); University of Texas at Dallas in Richardson, Texas (M.S. and Ph.D. in computer science)
Training: Postdoctoral research fellow in the Computational Biology Branch at NCBI/NLM and the Laboratory of Molecular Immunology at NHLBI
Came to NIH: In 2004 for training; became a tenure-track investigator in 2009
Selected professional activities: Editorial boards for PLOS ONE and Frontiers in Bioinformatics and Computational Biology; member of the International Society for Computational Biology
Outside Interests: Spending time with family; following the Dallas Cowboys
Research Interests: My laboratory seeks to understand how transcription regulators, proteins that determine which set of genes are turned on or off in a tissue-specific manner, control gene-expression programs during cellular development, differentiation, and pathogenesis. We use embryonic stem cells as a model system to study the gene networks controlling key cell-fate decisions.
We use integrative interdisciplinary approaches, merging computational biology, biochemistry, and functional genomics, to map and characterize gene networks that define cell states during development, differentiation, and homeostasis. Research within the group is largely data-driven, through computational analyses of published and in-house-generated high-throughput genomic and proteomic datasets, with the goal of generating testable hypotheses. The laboratory component provides the means not only to test some of the hypotheses that come out of computational analyses but also to perform biochemical experiments to gain mechanistic insights.
We have successfully identified and characterized many genes and pathways with previously unknown roles in embryonic stem-cell biology. Our current efforts include understanding how signaling cascades instruct epigenetic and transcription networks regulating cell-fate decisions.
ZHENG LI, PH.D., NIMH
Senior Investigator, Section on Synapse Development and Plasticity, National Institute of Mental Health
Education: Jilin University, Chang Chun, China (B.S. in biochemistry and molecular biology); Peking University, Beijing, China (M.S. in biochemistry); State University of New York at Stony Brook, Stony Brook, N.Y. (Ph.D. in neuroscience)
Training: Postdoctoral training on synapse development and plasticity at the Massachusetts Institute of Technology (Cambridge, Mass.)
Came to NIH: In 2006
Research interests: I am interested in the molecular and cellular mechanisms of synapse development and plasticity in normal and schizophrenic brains. My group uses a combination of optical imaging (two-photon and confocal), electrophysiology, and behavioral and genomic approaches to identify molecules and signaling pathways that control the function, structure, plasticity, and pathology of synapses.
Currently my research focuses on two areas: (1) the induction of the mechanism of long-term depression of synaptic transmission (LTD, a form of synaptic plasticity that leads to the weakening of synaptic response and synapse loss and is important for brain development and cognition); and (2) the function of schizophrenia risk genes in regulating synapse development and plasticity. We mainly conduct experiments with hippocampal neurons. The hippocampus is a brain structure essential for cognitive functions (such as learning and memory) and has been implicated in the pathophysiology of schizophrenia.
My group has uncovered a novel mechanism, mediated by cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases (caspases), for LTD induction in hippocampal neurons. Caspases have well-known functions in apoptosis (programmed cell death). However, the findings from my lab suggest that in the normal hippocampal neuron, caspases activate the key cellular process that is responsible for reducing synaptic strength without causing cell death.
My group also demonstrated that micro RNAs (miRNAs) are required for long-lasting maintenance of synaptic plasticity, identified “plasticity miRNAs,” and delineated the mechanisms by which they regulate synaptic plasticity.
Work from my group also indicates that the schizophrenia risk gene DTNBP1 modulates synapse maturation during adolescence, the typical age of onset for schizophrenia. This finding provides insights into the neuronal basis of reduced mental performance associated with schizophrenia.
IRINI SERETI, M.D., NIAID
Senior Investigator and Chief, HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases
Education: University of Athens, Zografou, Greece (M.D.); Duke University School of Medicine, Durham, N.C. (M.H.S. in clinical research training)
Training: Research for one year in human immunodeficiency virus immunology at Rush Presbyterian Hospital (Chicago); internship, residency, and chief residency in medicine at Northwestern University Feinberg School of Medicine (Chicago)
Came to NIH: In 1997 as a clinical associate in the Laboratory of Immunoregulation; became a staff clinician in 2003; appointed to a clinical tenure-track position in 2009
Selected professional activities: Editorial boards of Virus Eradication-Mediscript, Open Forum Infectious Diseases, and AIDS Research and Therapy; mentoring students
Outside interests: Traveling; running; going to the movies; spending time with family and friends
Research interests: The primary research focus of my group is the study of inflammatory complications in human immunodeficiency virus (HIV) including immune reconstitution inflammatory syndrome (IRIS). IRIS is an aberrant immune response—which frequently includes an intense inflammatory component—that can occur after the initiation of antiretroviral therapy (ART) in patients with HIV infection and severe CD4 lymphopenia. Chronically ART-treated patients on the other hand may experience noninfectious complications of HIV, including cardiovascular disease that seem to be driven by chronic residual immune activation and inflammation. A better understanding of the pathogenesis of acute and chronic inflammation after ART in HIV-infected people will help us identify appropriate therapeutic targets so we can improve the clinical management of these patients.
Our second interest is the study of etiology, pathogenesis, and possible therapeutic interventions of idiopathic CD4 lymphopenia (ICL). ICL is a rare, likely heterogeneous condition characterized by low CD4 T-cell counts in the absence of HIV or other known infection or disease that can cause lymphopenia.
SWEE LAY THEIN, M.D., F.R.C.P., M.R.C.P., D.Sc., NHLBI
Senior Investigator and Chief, Sickle Cell Branch, National Heart, Lung, and Blood Institute
Education: University of Malaya in Kuala Lumpur, Malaysia (B.S. and M.B. in medicine/surgery; D.Sc. in medicine); Royal College of Physicians in London (M.R.C.P., F.R.C.P. in medicine); Royal College of Pathologists in London (M.R.C.P. and F.R.C.P.. in hematology)
Training: Clinical and laboratory training in hematology at the U.K. Royal Postgraduate Medical School, Hammersmith Hospital (London), and at the Royal Free Hospital (London); research training at the Weatherall Institute of Molecular Medicine, University of Oxford (Oxford, U.K.)
Before coming to NIH: Professor of molecular hematology and consultant hematologist at King’s College London School of Medicine and King’s College Hospital NHS Foundation Trust (London); clinical director of the Red Cell Centre in King’s College Hospital (London)
Came to NIH: In 2015
Selected professional activities: Associate editor of Haematologica; editorial board of Blood; and feature editor for the digital Blood Hub on sickle cell anemia
Outside interests: Attending and listening to opera; hiking; and cooking
Research interests: My research team is examining the genetic factors underlying the phenotypic variability of beta-thalassemia disorders (inherited blood disorders that disrupt the normal production of hemoglobin, resulting in anemia) and sickle-cell disease. Both of these conditions are caused by mutations affecting the beta-globin gene.
People with beta thalassemia have reduced production of red blood cells; people with sickle-cell disease have abnormal “sickled” hemoglobin (HbS). HbS makes red blood cells rigid and sickle-shaped, and the cells then block the blood vessels, interrupt the oxygen supply to vital organs, and cause acute, intermittent pain. The rigid red blood cells are also fragile and easily destroyed, causing a life-long anemia.
Fetal hemoglobin (HbF) is the blood component primarily responsible for fetal oxygen transport and is present in infants until they are about six months old. The persistence of HbF beyond infancy is highly variable. High concentrations of HbF minimize many complications of sickle-cell disease and can increase life expectancy. Drug therapy can reactivate HbF production in both children and adults, reducing the severity of sickle-cell and beta-thalassemia symptoms.
By studying identical twins, my lab demonstrated that HbF concentrations are predominantly genetically controlled and that almost 90 percent of the difference in HbF concentrations from person to person can be accounted for by differences in genetic background. I have identified segments of DNA, called quantitative trait loci, on chromosome 11p (where the beta-globin gene is located), chromosome 6q, and the BCL11A gene on chromosome 2p. The loci, which have a beneficial clinical effect, stimulate HbF production in adults with and without sickle-cell disease or beta thalassemia.
My group is currently working on how the locus on chromosome 6q modifies HbF and how this process may provide a new genomic approach to increase HbF production therapeutically.
By using new genome technologies and deep phenotyping, my research team hopes to identify and validate genetic biomarkers that will allow for early detection and monitoring of severe sickle-cell complications. We plan to contribute to the discovery and development of drugs—including those that promote HbF synthesis and inhibit HbS polymerization—to treat sickle-cell disease.
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