T. Rajendra Kumar, Ph.D.

Ph.D., 1989; University of Delhi
Assistant Professor, Department of Pathology
Assistant Professor, Department of Molecular and Cellular Biology

Baylor College of Medicine, Building: BCM-Ben Taub Research Center
Room: BCMT-236
Phone: 713.798.5892
E~mail: tkumar@bcm.tmc.edu

RESEARCH INTERESTS:

Regulation of the hypothalamus-pituitary-gonadal (hpg) axis is a complex process. It involves a network of autocrine, paracrine and endocrine interactions among various factors. Alterations within this network can lead to abnormalities of reproductive tract development and may result in infertility and formation of gonadal cancers. Over the past several years, my research has been directed towards elucidating these interactions at all three levels of the hpg axis using both gain of function and loss of function transgenic and gene knockout approaches. Currently, research efforts in my lab are focused on three specific projects.

Activins are members of transforming growth factor-b superfamily and have diverse biological functions. They signal through transmembrane Ser/Thr kinase receptors. Recently, we discovered that activin receptor IIA knockout male mice demonstrate reproductive behavioral defects. These mice have a defect in the neuronal nitric oxide synthase (nNOS) activity in the medial preoptic area (mPOA) of the central nervous system. Many downstream targets of nNOS have been identified, however, very little is known about the upstream regulators of nNOS expression. The goal of this project is to delineate the mechanism of activin receptor IIA signaling in regulating the nNOS activity in the mPOA. These studies may unravel a novel mechanism of activin signal transduction in the mPOA that is critical for male sexual behavior.

The pituitary gonadotropins, LH and FSH regulate gonadal growth, differentiation, gametogenesis and steroidogenesis. The goals of the second project are to understand the mechanisms of gender-specific and differential regulation of pituitary gonadotropins, LH and FSH. Some of the approaches we are using include in silico subtraction to identify novel gonadotrope-specific genes/proteins, targeted expression of fluorescent reporters to gonadotropes in transgenic mice to selectively isolate pure populations of gonadotropes, and characterization of gonadotrope-enriched tumors induced by targeted expression of SV40 T antigen.

In the male, FSH and LH are critical trophic hormones for somatic cell development in the testis. They bind to G-protein coupled receptors and activate the cAMP pathway. FSH binds to Sertoli cells whereas LH binds to Leydig cells. The developmental fates of these cells are precisely regulated during a very narrow window of time that is essential for normal spermatogenesis. The goals of this third project are to delineate the stage-specific roles of FSH and LH during testis development, and to model human male reproductive disorders in mice. To achieve this, we generated gain of function and loss of function mouse models in which FSH or LH is either overexpressed or absent. We are using subtractive hybridization and microarrays to analyze changes in gene expression profiles during distinct phases of somatic cell development in the mouse testis. These studies may eventually lead to a better understanding of spermatogenesis and testicular cancers.

Selected Publications

Kumar TR, Lu H, Wang Y, and Matzuk MM. (1997) Follicle Stimulating hormone is required for ovarian follicle maturation but not male fertility. Nature Genetics 15: 201-204.

Kumar TR, Graham KE, Asa SL and Low MJ. (1998) Simian Virus 40-T Antigen induced gonadotroph adenomas: a model of human null-cell adenomas. Endocrinology 139:3342-3351.

Kumar TR. (2001) Neuroendocrine cell-specific immortalization using transgenic approaches. In: "Transgenics in Endocrinology" Ed: Matzuk MM, Brown CE and Kumar TR, Humana Press, Totowa, NJ, pp: 425-466.

Garcia-Campayo V, Kumar TR, and Boime I. (2002) Thyrotropin, follitropin, and chorionic gonadotropin expressed as a single multi-functional unit reveals remarkable permissiveness in receptor-ligand interactions. Endocrinology 143:3773-3778.

Baker PJ, Pakarinen P, Huhtaniemi IT, Abel, MH, Charlton HM, Kumar TR, and Shaughnessy PO. (2003) Failure of normal Leydig cell development in FSH receptor-deficient mice but not FSHb-deficient mice-role for constitutive receptor expression. Endocrinology 44:138-40.

Matzuk MM, Hadsell, LA, De Mayo F and Kumar TR. (2003) Overexpression of human chorionic gonadotropin in transgenic mice causes multiple reproductive defects. Biology of Reproduction, 338-346.