Areas of Interest
My long-standing research interest is the neural and endocrine control of the stress response. The mammalian stress response is mediated in large part by Corticotropin-Releasing Hormone (CRH, also known as CRF), a 41 amino acid peptide. In the neuroendocrine stress axis, hypothalamic CRH controls the release of adrenocorticotropin (ACTH) from the pituitary, which then controls glucocorticoid release from the adrenal gland. Within the brain, CRH acts as a neurotransmitter to control the behavioral, autonomic and immune responses to stress. Dysregulation of the CRH system has been linked to affective disorders, including major depression and anxiety disorders, and to addiction.
Our laboratory is interested in understanding the molecular regulation of the CRH system including the two classes of CRH receptors and the CRH-binding protein, particularly in stress, depression and relapse to addiction. The CRH-binding protein is distinct from the CRH receptors, but binds CRH with an equally high affinity. It appears to play multiple roles in the brain, from inhibiting CRH actions at CRH receptor 1 to enhancing CRH receptor 2 trafficking and activity. We study the mechanisms that regulate the CRH system in health and disease using: 1) transgenic and knockout mouse models for behavioral analyses; 2) in vivo stress and addiction studies; 3) cell culture analysis for biochemical signaling, trafficking and protein-protein interactions; 4) in vitro assays with purified CRH-binding protein and CRH receptors for binding affinity determinations; and 5) molecular cloning for studies on the molecular evolution of CRH-binding protein (structure and function) from insects to humans.
Honors & Awards
Kaiser Permanente Excellence in Pre-Clinical Teaching Award, University of Michigan Medical School, 2015
Endowment for Basic Sciences Teaching Award, University of Michigan Medical School, 2011
Research Scientist Recognition Award, University of Michigan, 2000
Independent Investigator Award, NARSAD, 1999–2001, 2003–2005
Career Development Award, University of Michigan Agenda for Women, 1999
Distinguished Achievement Award, Mental Health Research Institute, 1994
Young Investigator Award, NARSAD, 1990–1993, 1996–1999
Award for Outstanding Student Research and Teaching, American Chemical Society, 1981
Long-term alcohol consumption alters dorsal striatal dopamine release and regulation by D2 dopamine receptors in rhesus macaques.
Salinas AG, Mateo Y, Carlson VCC, Stinnett GS, Luo G, Seasholtz AF, Grant KA, Lovinger DM.
Neuropsychopharmacology. 2021, in press.
Deficits across multiple behavioral domains align with susceptibility to stress in 129S1/SvImJ mice.
Rodriguez G, Moore SJ, Neff RC, Glass ED, Stevenson TK, Stinnett GS, Seasholtz AF, Murphy GG, Cazares VA.
Neurobiol Stress. 2020; 13: 100262.
Enhanced CRFR1-dependent regulation of a ventral tegmental area to prelimbic cortex projection establishes susceptibility to stress-induced cocaine seeking.
Vranjkovic O, Van Newenhizen E, Nordness ME, Blacktop JM, Urbanik LA, Mathy JC, McReynolds JR, Miller AM, Doncheck EM, Kloehn TM, Stinnett GS, Gerndt CH, Ketchesin KD, Baker DA, Seasholtz AF, Mantsch JR.
J Neurosci. 2018; 38: 10657–71.
Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex.
Ketchesin KD, Huang NS, Seasholtz AF.
Front Neuroanat. 2017; 11: 90.
Corticotropin-releasing hormone-binding protein and stress: from invertebrates to humans.
Ketchesin KD, Stinnett GS, Seasholtz AF.
Stress. 2017; 20: 449–64.
Binge Drinking Decreases Corticotropin-Releasing Factor-Binding Protein Expression in the Medial Prefrontal Cortex of Mice.
Ketchesin KD, Stinnett GS, Seasholtz AF.
Alcohol Clin Exp Res. 2016; 40: 1641–50.
Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats.
Klampfl SM, Schramm MM, Stinnett GS, Bayerl DS, Seasholtz AF, Bosch OJ.
Horm Behav. 2016; 84: 136–44.
For a list of publications from PubMed, click HERE