CSB Faculty
Brent J. Thompson, Ph.D.
Assistant Professor
Vanderbilt University, 2005
(210)-567-3636
THOMPSONB3@UTHSCSA.EDU
I joined the Department of Cellular and Structural Biology in 2009 after completing my postdoctoral training at Vanderbilt University. I was one of the first postdoctoral fellows accepted into the Vanderbilt Scientist Educator program and as part of this program I was involved in teaching Gross Anatomy to the first year medical students. Currently I am a member of the American Association of Anatomists, and serve on the Advisory Committee for Young Anatomists. My postdoctoral research in the department of pharmacology focused on the development and analysis of knock-in mice carrying polymorphisms in the gene encoding the serotonin transporter (SERT). Altered activity of this transporter has been proposed to be involved in numerous neuropsychiatric and developmental disorders including major depression, anxiety, obsessive compulsive disorder (OCD), and autism. SERT is also believed to be the primary target for selective serotonin-reuptake inhibitor (SSRI)-class antidepressants and some tricyclic antidepressants used to treat these disorders. Molecular, biochemical and behavioral phenotyping of mice carrying SERT polymorphisms has revealed traits including alterations in serotonin homeostasis, increased brain iron levels, loss of response to SSRI class antidepressants, and changes in depression and anxiety related behavioral tasks.
Research Interests:
Research in the Thompson laboratory is focused on gaining a better understanding of how SSRI class antidepressants, such as Prozac, exert their clinical effects. SSRIs are thought to act by inhibiting serotonin clearance mediated by SERT. However, this assumption may be incomplete as it is well established that SSRIs have some affinity for other targets such the norepinephrine transporter and muscarinic, histaminergic and serotonergic receptors. Our understanding of the clinical effects of SSRIs is further confounded by the observation that SSRIs block serotonin uptake almost immediately, but the antidepressant effects can take weeks to manifest.
To better understand the mechanism of SSRI action, we have created a line of knock-in mice (SERT I172M) that have a loss of SERT sensitivity to multiple SSRIs, some tricyclic antidepressants and cocaine, while retaining normal serotonin transport. Ongoing studies are dissecting the biochemical and behavioral effects of SSRIs in an effort to define which effects are mediated by SERT blockade and which effects may be mediated by other targets of SSRIs. Additional studies are utilizing microarrays and quantitative RT-PCR to identify brain region specific alterations in gene expression following SSRI administration that may underlie the clinical effects of SSRIs. By utilizing the I172M SERT mice we will be able to distinguish SERT mediated changes in gene expression versus those mediated by other SSRI targets.
Presented at the American Society for Pharmacology and Experimental Therapeutics (ASPET), April 2009:
Platform session entitled "The Serotonin Transporter: Not Just for Neurons Anymore"
Research Techniques:
Production and analysis of transgenic mice
Behavioral phenotyping of mice
Pharmacological studies of the serotonin transporter (SERT)
SERT mediated gene expression
*Microarray, Real Time quantitative RT-PCR
PUBLICATIONS:
Veenstra-VanderWeele, J., Jessen, T.N, Thompson, B.J., Carter, M., Prasad, H.C., Steiner, J.A., Sutcliffe, J.S., Blakely, R.D., Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse. J. Neurodevelopmental Disorders in press 2009.
Carneiro AM, Airey DC, Thompson B, Zhu CB, Lu L, Chesler EJ, Erikson KM, Blakely RD. (2009) Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2047-52.
Thompson BJ, Washington MK, Kurre U, Singh M, Rula EY, Emeson RB. (2008) Protective roles of alpha-calcitonin and beta-calcitonin gene-related peptide in spontaneous and experimentally induced colitis. Dig Dis Sci. 2008 Jan;53(1):229-41.
Chastain CJ, Botschner M, Harrington GE, Thompson BJ, Mills SE, Sarath G, Chollet R. (2000) Further analysis of maize C(4) pyruvate,orthophosphate dikinase phosphorylation by its bifunctional regulatory protein using selective substitutions of the regulatory Thr-456 and catalytic His-458 residues. Arch Biochem Biophys. 2000 Mar 1;375(1):165-70.
Chastain CJ, Thompson BJ, and Chollet R. Maize recombinant C4-pyruvate, orthophosphate dikinase: Expression in Escherichia coli, partial purification, and characterization of the phosphorylatable protein. Photosynthesis Res. 1996; 49: 1 83-89.
