Audrey Seasholtz, Ph.D.

Professor, Biological Chemistry
Research Professor, Molecular & Behavioral Neuroscience Institute
Interim Director, Neuroscience Graduate Program

Ofc: 5035 BSRB

109 Zina Pitcher Place

Ann Arbor, MI 48109-2200

 

(734) 936-2072

Appointments

Biological Chemistry, Medical School
Molecular & Behavioral Neuroscience Institute

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

2015   Kaiser Permanente Excellence in Pre-Clinical Teaching Award, University of Michigan Medical School
2011   Endowment for Basic Sciences Teaching Award, University of Michigan Medical School
2000   Research Scientist Recognition Award, University of Michigan
1999-2001  Independent Investigator Award, NARSAD
1999   Career Development Award, University of Michigan Agenda for Women
1994   Distinguished Achievement Award, Mental Health Research Institute
1990-1993, 1996-1999  Young Investigator Award, NARSAD
1981   Award for Outstanding Student Research and Teaching, American Chemical Society

Published Articles or Reviews

Recent Publications

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.

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

For a list of publications from PubMed, click HERE