Audrey Seasholtz, PhD

Audrey Seasholtz, PhD

Director, Neuroscience Graduate Program
Professor, Biological Chemistry Research
Professor, Molecular and Behavioral Neuroscience Institute
5035 BSRB, Box 2200
aseashol@umich.edu
(734) 936-2072

1983                    Ph.D. Biological Chemistry, University of Michigan, Ann Arbor

1984-1985           Postdoctoral Fellow, Department of Chemistry, University of Oregon, Edward Herbert, Ph.D., mentor

1985-1987           Postdoctoral Fellow, Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, Oregon. Edward Herbert, Ph.D., mentor

1987-1988           Postdoctoral Fellow, Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, Oregon. James Douglass, Ph.D., mentor

1988-1996           Assistant Research Scientist, Mental Health Research Institute; Assistant Professor, Department of Biological Chemistry, University of Michigan

1996-2003           Associate Research Scientist, Mental Health Research Institute; Associate Professor, Department of Biological Chemistry, University of Michigan

2003-present      Research Professor, Molecular and Behavioral Neuroscience Institute; Professor, Department of Biological Chemistry, University of Michigan

2014-2018            Associate Director, Neuroscience Graduate Program, University of Michigan

2018-present       Interim Director, Neuroscience Graduate Program, University of Michigan

   

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 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.   

1990-1993                         NARSAD Young Investigator Award

1994                                  MHRI Distinguished Achievement Award for 1994

1999                                  Career Development Award, University of Michigan, Agenda for Women

1999-2001                         NARSAD Independent Investigator Award            

1999                                  Pfizer Investigator

 2000                                Research Scientist Recognition Award, University of Michigan

 2003-2005                        NARSAD Independent Investigator Award

 2004-2005                        Award for Teaching Excellence, Office of Medical Student Education, University of Michigan

 2011                                  EBS Basic Science Teaching Award, MBNI, University of Michigan

 2015                                  Kaiser Permanente Pre-Clinical Award for Teaching Excellence in Medical School Curriculum

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 Oct 10;11:90. doi: 10.3389/fnana.2017.00090. eCollection 2017. PMID: 29066956

Corticotropin-releasing hormone-binding protein and stress: from invertebrates to humans. Ketchesin KD, Stinnett GS, Seasholtz AF. Stress. 2017 May 18:1-16. doi: 10.1080/10253890.2017.1322575. [Epub ahead of print] PMID:28436309

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 Aug;40(8):1641-50. doi: 10.1111/acer.13119. Epub 2016 Jul 4. PMID: 27374820

Novel Roles for CRF-Binding Protein and CRF Receptor 2 in Binge Drinking. Ketchesin KD, Seasholtz AF. Alcohol Clin Exp Res. 2015 Dec;39(12):2296-8. doi: 10.1111/acer.12897. Epub 2015 Oct 28. PMID: 26509254

Pituitary CRH-binding protein and stress in female mice. Stinnett GS, Westphal NJ, Seasholtz AF. Physiol Behav. 2015 Oct 15;150:16-23. doi: 10.1016/j.physbeh.2015.02.050. Epub 2015 Feb 27. PMID: 25731977

Novel expression of type 1 corticotropin-releasing hormone receptor in multiple endocrine cell types in the murine anterior pituitary. Westphal NJ, Evans RT, Seasholtz AF. Endocrinology. 2009 Jan;150(1):260-7. doi: 10.1210/en.2008-0630. Epub 2008 Sep 11. PMID: 18787023

Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. Rozeboom AM, Akil H, Seasholtz AF. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4688-93. Epub 2007 Mar 5. PMID: 17360585

CRH-BP: the regulation and function of a phylogenetically conserved binding protein. Westphal NJ, Seasholtz AF. Front Biosci. 2006 May 1;11:1878-91. Review. PMID: 16368564

Corticotropin-releasing factor is cytoprotective in Xenopus tadpole tail: coordination of ligand, receptor, and binding protein in tail muscle cell survival. Boorse GC, Kholdani CA, Seasholtz AF, Denver RJ. Endocrinology. 2006 Mar;147(3):1498-507. Epub 2005 Dec 1. PMID:16322064

Sexually dimorphic expression of corticotropin-releasing hormone-binding protein in the mouse pituitary. Speert DB, McClennen SJ, Seasholtz AF. Endocrinology. 2002 Dec;143(12):4730-41. PMID:12446601

Mouse models for psychiatric disorders. Seong E, Seasholtz AF, Burmeister M. Trends Genet. 2002 Dec;18(12):643-50. Review. PMID:12446150

Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals. Seasholtz AF, Valverde RA, Denver RJ. J Endocrinol. 2002 Oct;175(1):89-97. Review. PMID: 12379493

Mouse models of altered CRH-binding protein expression. Seasholtz AF, Burrows HL, Karolyi IJ, Camper SA. Peptides. 2001 May;22(5):743-51. Review. PMID:11337087

Biochemical characterization and expression analysis of the Xenopus laevis corticotropin-releasing hormone binding protein. Valverde RA, Seasholtz AF, Cortright DN, Denver RJ. Mol Cell Endocrinol. 2001 Feb 28;173(1-2):29-40. PMID:11223175

Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice. Karolyi IJ, Burrows HL, Ramesh TM, Nakajima M, Lesh JS, Seong E, Camper SA, Seasholtz AF. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11595-600. PMID: 10500222

Regulation of pituitary corticotropin-releasing hormone-binding protein messenger ribonucleic acid levels by restraint stress and adrenalectomy. McClennen SJ, Cortright DN, Seasholtz AF. Endocrinology. 1998 Nov;139(11):4435-41. PMID: 9794449

Excess corticotropin releasing hormone-binding protein in the hypothalamic-pituitary-adrenal axis in transgenic mice. Burrows HL, Nakajima M, Lesh JS, Goosens KA, Samuelson LC, Inui A, Camper SA, Seasholtz AF. J Clin Invest. 1998 Apr 1;101(7):1439-47. PMID: 9525987

Lab website

734-936-0564