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More about
Dr. Kovats:

Dr. Kovats' CV in brief

Publications

Arthritis and Immunology Research Program

Susan Kovats, Ph.D. Assistant Member, Arthritis and Immunology Research Program

Research Interests
Sex biases in autoimmunity and infection suggest that steroid sex hormones directly modulate the function of immune cells expressing estrogen receptors (ER). Antigen specific T cell responses depend on the function of dendritic cells (DC) to initiate innate and adaptive immunity. DC regulate protective immunity to pathogen proteins or tumor antigens, but also may elicit detrimental autoimmune responses. A primary focus of my lab has been the study of the role of estrogen in DC differentiation and function. Other projects focus on the role of antigen presenting cells during the autoimmune diseases rheumatoid arthritis and lupus.

We have found that estrogen promotes the differentiation of functional DC from undifferentiated myeloid progenitors in murine bone marrow. Estrogen acting via ER is required for the development of a subset of DC exhibiting features of epidermal Langerhans cells. We also studied the effects of selective ER modulators (SERM) such as tamoxifen, used for breast cancer prevention, which may act as ER agonists or antagonists depending on the target cell type. We found that inclusion of tamoxifen reduces DC numbers during in vitro differentiation, and those DC that do develop are hyporesponsive to activation signals, suggesting that systemic SERM treatment might alter DC function in response to inflammatory stimuli.

Current studies involve definition of estrogen-responsive DC progenitors in bone marrow, which will facilitate future studies to distinguish among the potential effects of estrogen on survival, proliferation or induction of a specific differentiation program in DC precursors. Secondly, ongoing studies are testing the hypothesis that variable systemic estrogen levels or exposure to SERM result in differences in DC number or function in vivo. These studies are being done in a model system in which DC mediated antigen presentation and T cell activation in vivo may be monitored after systemic estrogen response manipulation.

The long-term goals of these studies are to define the molecular mechanisms by which estrogen promotes DC differentiation from bone marrow progenitors, and to understand how variable ER-mediated responses to estrogen or SERM modulate antigen specific immune responses in vivo. Ultimately we will apply the information gained from such studies to murine models of autoimmunity.

Joined OMRF Scientific Staff in 2005.

Mailing Address
Arthritis and Immunology Research Program, MS 24
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-8583
Fax: (405) 271-7063
E-mail: Susan-Kovats@omrf.org