Dr. Mark Brennan
Professor
Email: Dr. Mark Brennan
Phone Number: 502-852-1646
Fax: 502-852-6222
Address: 319 Abraham Flexner Way, Room 512
Louisville, KY 40202
PhD, 1981, Indiana University
Area of Interest:
Genetically complex diseases and genetic regulatory mechanisms.
One of the most exciting frontiers in medical genetics is study of so-called genetically complex diseases – those diseases involving multiple genes and environmental components. Dr. Brennan’s group is working in collaboration with psychologists and psychiatrists to map and analyze genes involved in genetically complex neuropsychiatric diseases such as schizophrenia, bipolar disorder, and obsessive-compulsive disorder. The lab has a 20-year history of studying how naturally-occurring sequence variation can alter the regulatory mechanisms involved in transcriptional regulation, translational regulation and chromosome structure. The importance of regulatory variation in human health and disease was largely underappreciated until recent advances in the Human Genome Project highlighted the role of so-called “junk” DNA in gene regulation. For over two decades, Dr. Brennan’s group has used genetic transformation of Drosophila as a tool to elucidate the mechanisms by which naturally occurring sequence variation can alter gene regulation. As one example, they have studied a transcriptional regulatory element (called an insulator) that is carried on a retrotransposon in Drosophila so as to better understand the mechanisms by which such chromosomal elements block interactions of enhancers with their target promoters. Presently, the lab is focused on identifying genetic variants associated with neuropsychiatric diseases in humans and studying the mechanisms by which these exert their effects.
Selected Publications:
Brennan MD, Condra J. 2005. Transmission disequilibrium suggests a role for the sulfotransferase-4A1 gene in schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 2005 Nov 5;139(1):69-72.
Brennan, M.D. 2001. High throughput genotyping technologies for pharmacogenomics. Am J Pharmacogenomics. 2001;1(4):295-302.
Wei, W. and Brennan, M.D. 2001. The gypsy insulator can act as a promoter-specific transcriptional stimulator. Mol Cell Biol. 2001 Nov;21(22):7714-20.
Brennan, M.D., H.L. Neibergs, K. Phillips, and S. Moseley. 2000. Polymorphic markers for the arylsulfatase A gene reveal a greatly expanded meiotic map for the human 22q telomomeric region. Genomics 63: 430-432.
Wei, W., and M.D. Brennan. 2000. Polarity of transcriptional enhancement revealed by an insulator element. Proc. Natl. Acad. Sci. USA 97:14318-14523.
McKenzie, R. W. and M. D. Brennan. 1998. Cis-acting sequences controlling the adult-specific transcription pattern of the Drosophila affinidisjuncta Adh gene. Dev. Genetics 23: 119-127.
McKenzie, R. W. and M. D. Brennan. 1998. Cis-acting sequences contributing to expression of the Drosophila affinidisjuncta Adh gene in both larvae and adults. Insect Biochem. Mol. Biol. 28: 869-874.
Winner, E. J., R. A. Prough and M. D. Brennan. 1997. Human NAD(P)H: quinone oxidoreductase induction in human hepatoma cells after exposure to industrial acrylates, phenolics, and metals. Drug Metab. Dispos. 25: 175-181.
Brennan, M. D., P. A. Thorpe, J. Hu and W.J. Dickinson. 1996. Molecular organization of the alcohol dehydrogenase loci of Drosophila grimshawi and Drosophila hawaiiensis. Gene 181: 51-55.
McKenzie, R.W. and M.D. Brennan (1996) The two small introns of the Drosophila affinidisjuncta Adh gene are required for normal transcription. Nucl Acids Res 24, 3635-3642.
Hu, J., H. Qazzaz and M.D. Brennan (1995) A transcriptional role for conserved footprinting sequences within the larval promoter of a Drosophila alcohol dehydrogenase gene. J Mol Biol 249, 259-269.
Wu, C.-Y. and M.D. Brennan (1993) Similar tissue-specific expression for the Adh genes from different Drosophila species is mediated by distinct arrangements of cis-acting sequences. Mol Gen Genetics 240, 58-64.
McKenzie, R.W., J. Hu and M.D. Brennan (1994) Redundant cis-acting elements control expression of the Drosophila affinidisjuncta Adh gene in the larval fat body. Nucl Acids Res 22, 1257-1264.
