Graduate Studies Faculty
Martin J. Kelly, Ph.D.
Programs:Neuroscience Graduate Program
Physiology & Pharmacology
Program in Molecular & Cellular Biosciences
Research Interests:hypothalamic neurons, homeostasis, reward, dopamine, beta-endorphin,serotonin, estrogen,leptin,signaling cascades » PubMed Listing
Preceptor RotationsDr. Kelly has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Kelly has not indicated availability as a mentor at this time.
Summary of Current Research
Estradiol, K+ Channels and Homeostasis
The gonadal steroid 17beta-estradiol is a pleiotropic hormone that has widespread actions not only on reproductive tissues but also has pronounced effects in the central nervous system (CNS). For over twenty-five years, my laboratory has been studying the actions of estradiol in the brain, specifically in hypothalamic neurons that control homeostasis and behavior, using molecular, electrophysiological and behavioral techniques. We have discovered a novel estrogenic signaling pathway that can better explain the differences between females and males, not only in terms of the reproductive cycle but also differences in stress responses, motivation and mood. These actions of estradiol are similar to the effects of neurotransmitters like serotonin in the CNS. We use an in vitro slice preparation to do whole-cell patch recording in hypothalamic neurons followed by single cell reverse transcription-polymerase chain reaction (RT-PCR) to identify changes in the expression of receptors and K+ channel transcripts during different physiological states.
In collaboration with Drs. Oline Ronnekleiv and Tom Scanlan in the Department of Physiology and Pharmacology, we have developed a novel non-steroidal compound that targets a membrane-associated estrogen receptor (mER), called STX that mimics the actions of estradiol in POMC neurons. We have discovered that estradiol acts directly on these neurons via a novel estrogen G protein-coupled receptor to alter their activity. This unique membrane-associated estrogen receptor is Gq-coupled to activation of a phospholipase C-protein kinase C-protein kinase A pathway leading to desensitization of mu-opioid and GABAB receptors in POMC neurons. We use two different experimental models. One model is the female guinea pig whose reproductive cycle mimics that of the human; another model is the transgenic female mouse in which POMC or NPY neurons are tagged with green fluorescence protein in order to selectively target these neurons in the brain slice preparation. Using these models we are studying the mER signaling pathway and its cross-talk with metabolic hormone (i.e., leptin and insulin) signaling pathways in POMC and NPY neurons.
As proof of principle, we have identified several homeostatic processes (e.g., control of reproduction, energy and temperature homeostsis) that are regulated by STX. Moreover, STX is fully efficacious in protecting hippocampal neurons in a rodent stroke model.
Finally, we have utilized a brain-specific, guinea pig microarray chip, developed in collaboration with Dr. Oline Ronnekleiv, to characterize the effects of estradiol on gene regulation. We have used this gene chip to identify estradiol-regulated genes in POMC and NPY neurons that are important for neuronal excitability (e.g., Ca2+, K+ channels) and signal transduction.
Ph.D., University of Texas Southwestern Medical School, 1976