T H E   N I H   C A T A L Y S T     S E P T E M B E R  –  O C T O B E R   2007

P E O P L E  

ON TENURE TRACK

Kristin Tarbell

Kristin Tarbell joined the NIDDK Diabetes Branch in July this year, establishing her own laboratory where she will continue her research in T-cell tolerance and how this goes awry in autoimmune diseases such as type 1 diabetes.

Normally, T cells that recognize antigens from the body are inactivated, thus reducing the response against self and developing specificity against foreign antigens. In autoimmune disease, however, T cells that recognize self are not inactivated; in the case of type 1 diabetes, they proceed to attack the host’s own insulin-producing pancreatic b-cells.

While a postdoc at Rockefeller University, Tarbell and her advisor, Ralph Steinman, demonstrated that increases in the number of regulatory T cells could protect insulin-producing b-cells in mice from attack by their own immune system. Regulatory T cells are a rare cell type that can block the response of other T cells and thus could be key to controlling autoimmune diseases. These results suggested that autoimmunity could be reversed and brought to light the role of dendritic cells in this type of T-cell tolerance.

Tarbell’s research here will focus on understanding how regulatory T cells work and the role that dendritic cells play in promoting tolerance of T cells. She will explore the signals between regulatory T cells and dendritic cells. In addition, Tarbell will address the development of autoimmunity and how the immune system environment, specifically the role of dendritic cells, differs to allow tolerance of T cells targeting self-antigens.

Drawing on NIDDK’s unique and extensive resource of samples from patients with type 1 diabetes, Tarbell also plans to expand her current research to develop better T-cell assays to facilitate the study of the immune system’s response against pancreatic cell antigens in type 1 diabetes. These responses, although enough to cause disease, are currently tough to measure, says Tarbell. Improvement in these types of assays will assist in translating Tarbell’s results in mice to human patients.

Julie Wallace


Ondine von Ehrenstein

Ondine von Ehrenstein joined the NICHD’s Division of Epidemiology, Statistics & Prevention Research this summer, bringing with her many years of expertise in international epidemiology and risk assessment in the area of childhood diseases, with an emphasis on environmental exposure.

Among her many projects is a study examining the relationship between childhood respiratory and atopic illnesses and various environmental and lifestyle factors, including indoor and outdoor air pollution and exposures found in traditional farming environments.

Studying developing and transitional countries, where exposures can be much higher and differ from those in highly developed countries, can provide new insights into disease etiologies and risks, she said.

Von Ehrenstein hopes to study novel biomarkers for exposure, particularly in pregnancy and early childhood, with noninvasive specimen collections. She is also pursuing further analyses of the NICHD Collaborative Perinatal Project, a classic longitudinal study from 1959 to 1974 that followed nearly 60,000 pregnancies and births until the children were seven years old, primarily designed to assess neurodevelopment. This study is a rich source of biomedical, environmental, and socioeconomic information.

Before arriving at NICHD, von Ehrenstein was a researcher for more than four years at the University of California, Berkeley, where she directed research on arsenic exposure and childhood development and reproduction in West Bengal, India.

Her group found a sixfold increase in stillbirth for mothers exposed to arsenic from well water, as well as reductions in cognitive development in school-aged children.

Earlier, during her tenure as a scientist and program manager at the WHO Regional Office for Europe in Rome, she co-edited "Children’s Health and Environment: A Review of Evidence."

This 220-page report outlined environmental risks to children who—because of their unique susceptibility, such as a higher skin-to-body-weight ratio and exposures occurring during critical windows of development—suffer from up to 40 percent of the global burden of disease attributable to environmental factors.

Von Ehrenstein conducted her doctoral work in epidemiology at the Children’s Hospital of the University of Munich and at the School of Public Health in Bielefeld, Germany, and she has a background in laboratory biology and public health.

Christopher Wanjek


Cuilin Zhang

Cuilin Zhang is an epidemiologist focusing on genetic and lifestyle risk factors influencing gestational diabetes and chronic metabolic diseases. She joined the NICHD Epidemiology Branch in June.

Zhang is a graduate of Beijing Medical University, and she earned her M.P.H. and a Ph.D. in epidemiology from the University of Washington in Seattle. Continuing to work her way eastward, she was a researcher at Harvard School of Public Health for three years before coming to NIH.

Zhang says that recent developments in high-throughput biotechnology and genomic science have allowed—and challenged—epidemiologists to go beyond the assessment of environmental risk factors to sensibly incorporate, analyze, and interpret emerging genetic data in the context of other epidemiologic variables.

She hopes, therefore, to partner with geneticists, metabolic biologists, and behavioral scientists at NIH to more fully investigate the interplay of genetic and nongenetic biological markers and lifestyle choices.

Her research activities thus far can be broadly characterized as clinically based case-control and prospective studies on genetic and biochemical markers for gestational diabetes and pre-eclampsia; large-scale prospective studies on lifestyle and gestational diabetes; longitudinal studies on long-term implications of vascular and metabolic disorders in pregnancy; and nested case-control studies of the relationships among genetics, biomarkers, diet, and lifestyle and the risk of type 2 diabetes and related cardiovascular complications.

Zhang calls pregnancy a "stress test" for women predisposed to chronic metabolic diseases. By studying pregnant women she hopes to elicit not only the etiology of metabolic disorders in pregnancy but also underlying biological changes that lead to early stages of type 2 diabetes and cardiovascular disease.

Her research on gestational diabetes has examined the diet and lifestyle of women before and after pregnancy. Based on data from the Nurses’ Health Study II, Zhang and her Harvard colleagues found that women who were more physically active and had a prudent diet before pregnancy had significantly lower risk of gestational diabetes. For example, they found that each 10-gm rise in daily fiber consumption was associated with 26 percent reduced risk.

Zhang hopes to continue to understand the proper "dose" of prevention of pregnancy-related complications for women hoping to become pregnant.

Christopher Wanjek


 

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