Professor and Chair, Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, USA
PhD – University of Michigan, Ann Arbor, MI
Postdoctoral Scholar – Reproductive Endocrinology Program, University of Michigan, Ann Arbor, MI
Postdoctoral Fellow – Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY
A major, long-standing interest of our lab is in understanding the neural and neuroendocrine circuitry by which the brain controls reproduction. Working with Bob Goodman (West Virginia University) and Lique Coolen (University of Mississippi Medical Center), in 2007, we identified a single subset of neurons in the arcuate nucleus of the hypothalamus that co-expresses three neuropeptides, kisspeptin, neurokinin B and dynorphin, termed “KNDy” neurons, that appear to form a key component of the GnRH pulse generator. Since that time compelling evidence has accumulated supporting the view that KNDy cells serve as a final common pathway for external and internal regulatory signals that control GnRH secretion in a wide range of mammals. In collaboration with Vasantha Padmanabhan (University of Michigan), we have also focused on the potential role of KNDy cells in reproductive disease. Specifically, we have found alterations in the balance of KNDy peptides, and in the morphology and connections of KNDy cells, in an animal model of polycystic ovarian syndrome (PCOS) that may contribute to the dysfunction of steroid feedback control seen in women with that disorder.
The primary animal model we use in our studies of GnRH and KNDy neurons is the sheep. The sheep has several advantages as an experimental model for neuroendocrine research, most notably the ability to directly measure GnRH from pituitary portal blood in unanesthetized animals. This allows us to obtain precise and repeated measurements of GnRH release during pulsatile and surge modes of GnRH secretion. Coupled with the relatively large size of the sheep brain, this enables us to perform experiments interrogating structure-function relationships in the brain at a detailed level of analysis using a variety of molecular, pharmacologic and physiological techniques.