Audrey Seasholtz, Ph.D.
Research Professor, MBNI
Professor, Department of Biological Chemistry

5035 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-2200

aseashol@umich.edu

(734) 936-2072

Current Research Interests:

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.

Selected Publications:

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.
Enhanced CRFR1-dependent regulation of a ventral tegmental area to prelimbic cortex projection establishes susceptibility to stress-induced cocaine seeking.
J Neurosci. 2018; 38:10657-71.

Ketchesin KD, Huang NS, Seasholtz AF.
Cell type-specific expression of corticotropin-releasing hormone-binding protein in GABAergic interneurons in the prefrontal Cortex.
Front Neuroanat. 2017; 11:90.

Ketchesin KD, Stinnett GS, Seasholtz AF.
Corticotropin-releasing hormone-binding protein and stress: from invertebrates to humans.
Stress. 2017; 20:449-64.

Ketchesin KD, Stinnett GS, Seasholtz AF.
Binge drinking decreases corticotropin-releasing factor-binding protein expression in the medial prefrontal cortex of mice.
Alcohol Clin Exp Res. 2016; 40:1641-50.

Stinnett GS, Westphal NJ, Seasholtz AF.
Pituitary CRH-binding protein and stress in female mice.
Physiol Behav. 2015; 150:16-23.