Colleagues: Recently Tenured

LESLIE BAIER, PH.D., NIDDK

Senior Investigator, Phoenix Epidemiology and Clinical Research Branch

Education: Lawrence University, Appleton, Wis. (B.A. in biology and chemistry); University of Michigan Medical School, Ann Arbor, Mich. (Ph.D. in cell and molecular biology)
Training: Postdoctoral fellowship at Arizona State University (Phoenix)
Came to NIH: In 1993
Selected professional activities: Adjunct professor at University of Arizona College of Medicine (Tucson, Ariz.) and Arizona State University (Phoenix); very active in mentoring students in high school, community college, and undergraduate programs, in addition to postbaccalaureate and postdoctoral trainees
Outside interests: Dancing (recently traded her ballet pointe shoes for Zumba sneakers); making pilgrimages to Nordstrom with her daughters; playing endless games of Candy Land with her grandchildren

Research interests: My lab is identifying and characterizing susceptibility genes for obesity and type 2 diabetes among the Pima Indians of Arizona. This Native American population has high rates of obesity and the highest reported prevalence of type 2 diabetes of any population worldwide. Multiple studies have shown that heritable factors underlie a significant portion of the variation in risk for these disorders; environmental variables influence the expression of this genetic susceptibility. We are comparing the genetic details of Pima Indians with and without obesity and type 2 diabetes.

Using genome-wide association studies (GWAS), we have identified common genetic variants associated with type 2 diabetes, obesity, prediabetes, or preobesity traits in Pima Indians. We also identified several strong and reproducible associations not reported in other GWAS, a finding that suggests ethnic-specific heterogeneity in risk factors for these common diseases.

We are conducting other studies to test the hypothesis that multiple rare variants may underlie some proportion of the variance we have identified. We recently completed whole-exome sequencing on 180 Pima Indians and whole-genome sequencing on 135 Pima Indians. We also have genome-wide expression data from human skeletal muscle and adipose biopsies from more than 200 nondiabetic Pima Indians. We are using these data to identify expression profiles that may predict the onset of diabetes. We are also merging expression data with GWAS genotypic data and whole-genome sequence data to identify factors that may contribute to these polygenic diseases.
We believe that understanding and quantifying specific genetically determined susceptibility factors could help prevent these diseases by identifying at-risk individuals. The research could also identify novel therapeutic and personalized targets, which may lead to improved treatments.

MARK HOON, PH.D., NIDCR

Senior Investigator, Laboratory of Sensory Biology, Molecular Genetics Unit

Education: University of Birmingham, Birmingham, U.K. (B.S. in biochemistry); University of Leeds, Leeds, U.K. (Ph.D. in biochemistry)
Training: Postdoctoral training in microbiology at the Albert Ludwigs University of Freiburg (Freiburg im Breisgau, Germany)
Came to NIH: In 1992 for training; in 1999 became a staff scientist; in 2006 became a tenure-track investigator
Selected professional activities: Member of the Society for Neuroscience and of the American Pain Society
Outside interests: Long-distance running

Research interests: Several years ago I started as a tenure-track investigator in what was, for me, a completely new area of sensory biology. Previously, in the lab of Nick Ryba, I had studied the sense of taste. As a tenure-track investigator I made a change and set up a lab that investigated the biology of somatosensation (thermal and nociceptive stimulation and the sense of touch). We particularly want to understand how molecules and peripheral sensory neurons transform stimuli into membrane depolarization and how these cells transmit signals to neural relays in the brain. We have been using a variety of techniques including molecular genetics and behavioral and electrophysiological testing, as well as cell-culture and biochemical assays.

Our studies have provided new information about the mechanisms by which somatosensory receptors transduce and transmit signals. Recently, we identified a neurotransmitter called natriuretic polypeptide B (Nppb) that is released in the spinal cord and carries the sensation of itch to the brain. We showed that mice lacking either Nppb or cells expressing its receptor in the spinal cord did not scratch themselves when administered itching agents, but were still sensitive to pain. These and related studies will allow us to continue to determine crucial molecules and cells required for specific types of somatosensory input, including those involved in sensing pain and touch. Ultimately, we would like to establish how the brain distinguishes different types of stimuli.

STEPHANIE STUDENSKI, M.D., M.P.H., NIA

Senior Investigator, Longitudinal Studies Section

Education: University of Kansas, Kansas City, Kansas (B.S.N. and M.D.); University of North Carolina, Chapel Hill (M.P.H.)
Training: Residency in internal medicine and fellowships in rheumatology–genetic disease and in geriatrics, Duke University Medical Center (Durham, N.C.)
Before coming to NIH: Professor of medicine and director of research, Division of Geriatric Medicine, University of Pittsburgh; staff physician at Geriatric Research, Education, and Clinical Center, VA Pittsburgh Healthcare System; previously held faculty positions at Duke University Medical Center and at University of Kansas Medical Center and was director of the latter’s Center on Aging
Came to NIH: In 2014
Selected professional activities: Associate Editor, Journal of Gerontology Medical Sciences; member, NIA Council; former chair of the Aging Systems and Geriatrics Study Section and of the Geriatrics and Rehab Medicine Study Section
Outside interests: Hiking; cooking; playing piano

Research interests: My research focuses on the causes and consequences of and effective interventions for balance and mobility disorders in older adults. These common and disabling problems increase in frequency as people age. I strive to understand balance and mobility problems that occur with obvious conditions such as stroke, arthritis, Parkinson disease, and hip fractures as well as those that surface with other, less obvious conditions such as peripheral neuropathy (numb feet), vision loss, muscle dysfunction, and slowed neural-processing speed.

My research methods include biomechanics, neuroimaging, body-composition techniques, and neuropsychologic testing. I have led several clinical trials using novel forms of exercise—such as motor-learning practice and interactive video dance games–to promote balance and mobility in older persons. I have also led collaborations to pool data from multiple studies to develop precise estimates of the effect of walking speed or muscle mass on clinically relevant outcomes such as survival or disability.

My recent work has focused on subclinical changes in the brain that contribute to alterations in walking behavior with age. Beyond evidence of regional gray-matter atrophy and white-matter disease, there are subtle changes in white-matter tracts (detected using diffusion tensor imaging) that contribute to changes in walking speed and gait variability. My clinical trials on motor learning, using repeated practice or interactive video games, are designed to promote smoothness and efficiency of gait as well as sensorimotor processing. I have also assessed how regional brain white-matter disease affects responses to interventions.

BRYAN TRAYNOR, M.D., PH.D., NIA

Senior Investigator and Chief of the Neuromuscular Diseases Research Section, Laboratory of Neurogenetics

Education: University College Dublin Medical School (M.B., B.Ch., M.D.; Ph.D. in the genetics of amyotrophic lateral sclerosis, ALS); Harvard University and Massachusetts Institute of Technology, Cambridge (M.M.Sc. in drug discovery and clinical-trials design)
Training: Internal medicine residency, St. Vincent’s University Hospital (Dublin); neurology residency and fellowship, National Neuroscience Center of Ireland, Beaumont Hospital (Dublin); neurology residency and ALS-neuromuscular fellowship at Massachusetts General Hospital and Brigham and Women’s Hospital (Boston)
Before coming to NIH: Instructor and staff neurologist at Harvard Medical School (Boston) and Massachusetts General Hospital
Came to NIH: In 2005 as a clinical associate
Selected professional activities: Adjunct faculty member of Neurology Department at Johns Hopkins Medicine (Baltimore); member of the Scientific Review Committee of the ALS Association and of the Integration Panels for the Department of Defense ALS Research Program and the Department of Defense Alzheimer’s Research Program

Research interests: My laboratory is best known for its work aimed at understanding the genetic etiology of amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) and related neurodegenerative disorders, such as frontotemporal dementia (FTD). We apply advanced genomic technologies to unravel the etiology of our diseases of interest.

We have had many notable successes over the years: My lab published the first genome-wide association study of ALS (2007); was the first to identify an association signal for ALS on the short arm of chromosome 9 in the Finnish founder population (2010); discovered that mutations in the VCP gene are responsible for a significant fraction of familial ALS (2010); and recently published that mutations in the MATR3 gene are another cause of familial ALS (2014). In 2011, I led the international consortium that identified a pathogenic hexanucleotide repeat expansion in the C9ORF72 gene as the underlying mutation in a large proportion of familial ALS and FTD, as well as in the more common sporadic forms of both neurodegenerative diseases.

ADRIAN WIESTNER, M.D., PH.D., NHLBI

Senior Investigator, Laboratory of Lymphoid Malignancies; Attending Physician, Hematology Branch

Education: University of Basel Medical School, Basel, Switzerland (M.D.; Ph.D. in genetics)
Training: Residency in internal medicine, University Hospital in Basel, Switzerland
Came to NIH: In 2000 as a hematology fellow in NHLBI; in 2003 became a clinical fellow at NCI; in 2004, joined NHLBI as a tenure-track investigator and attending physician
Selected professional activities: Medically responsible investigator and IND (investigational new drug) sponsor on clinical trials investigating novel agents for chronic lymphocytic leukemia
Outside interests: Traveling; playing tennis; skiing; sailing

Research interests: I am interested in B-cell lymphoproliferative diseases, especially chronic lymphocytic leukemia (CLL). CLL is the most common leukemia in the United States and affects mostly older adults. I want to better understand how the tumor cells grow and to develop novel agents and treatment strategies that we can test in clinical trials.

My lab is pursuing two complementary approaches. First, using leukemic cells from CLL patients who are enrolled in a natural-history study, we are studying signaling pathways that drive the proliferation and survival of the leukemia. We compared tumor cells isolated from blood, bone marrow, and lymph nodes, and we identified B-cell-receptor signaling as a key pathway in CLL. We have confirmed in several clinical trials that inhibitors of B-cell-receptor signaling may be useful as a targeted therapy. We are conducting a study using one such inhibitor, called ibrutinib, in patients with a genetic lesion (deletion of chromosome 17p) that predicts poor survival with standard treatment. Preliminary results are very encouraging and suggest that ibrutinib may be able to overcome limitations of current treatments and improve survival.

In our second approach, we are trying to understand the effect of a given treatment on tumor cells. Although most clinical studies record the details of responses to and side effects of treatment, they rarely sample and analyze tumors before and during treatment.

At the Clinical Center such studies are possible, thanks to its unique infrastructure and our patients, who are often willing to undergo additional procedures to provide research samples. By analyzing tumor cells during therapy, we learn how the cells react and adapt to treatment. Such adaptations may allow the cells to escape and become resistant to further therapy. We have applied this approach successfully to several studies and types of therapies. In addition to identifying mechanisms of treatment resistance, we have obtained information that could lead to novel therapies, an avenue that we are actively pursuing.

DMITRI ZAYKIN, PH.D., NIEHS

Senior Investigator, Biostatistics Branch

Education: North Carolina State University, Raleigh, N.C. (Ph.D. in biomathematics, minor in statistics); Far Eastern State University, Vladivostok, Russia (graduate degree—M.S. equivalent—in biology and population genetics)
Before coming to NIH: Research fellow, Institute of Marine Biology (Vladivostok); visiting scholar, North Carolina State University; investigator, GlaxoSmithKline (Durham, N.C.)
Came to NIH: In 2004 as a tenure-track investigator
Selected professional activities: Adjunct associate professor, Center for Neurosensory Disorders, University of North Carolina at Chapel Hill; member of the American Statistical Association and of the American Society of Human Genetics
Outside Interests: Listening to classical music; reading; weightlifting; science is also a hobby, not just a job

Research Interests: Our group uses statistical methodology to discover relationships between genetic variation and phenotypic traits. These relationships can now be discovered using high-throughput genotyping data to reveal genetic polymorphisms involved in disease susceptibility, response to medications, and differential reactions to environmental exposures. Development of statistical methods to accompany technological advances is essential for treating and preventing disease and enhancing the quality of life.

We develop efficient approaches for detecting and characterizing genetic associations with discrete and quantitative traits while taking into account the large and expanding scale of genomic data, environmental exposures, and gene-environment interactions. We devise strategies that are useful not only for genetic applications, but also for the analysis of other kinds of multidimensional data in which many statistical hypotheses are being evaluated. Some examples of where our techniques are applicable include studies involving epigenetic effects of exposures, metabolomics, and differential gene expression. Our collaborative research continues to bring modern statistical methodology to epidemiological studies of complex human diseases.

Zaykin write-up submitted by Robin Arnette (NIEHS)