Dr Michael H. Court, BVSc, PhD: Dr Court is the laboratory director and principal investigator for the grants that support the laboratory. He originally graduated from the University of Queensland in Australia with a DVM equivalent degree (BVSc, 1981) and, after postdoctoral training at the University of Sydney and Tufts University School of Veterinary Medicine, joined the faculty at Tufts as a board-certified veterinary anesthesiologist eventually becoming Director of Clinical Anesthesia. In 1992 he entered a PhD program in the Pharmacology Department at Tufts under the mentorship of Dr David Greenblatt, the current Department chairman.
The PhD thesis project entailed identifying the molecular genetic basis for deficient glucuronidation of acetaminophen (Tylenol) and other drugs by domestic cats. This work showed that cats lack many of the UDP-glucuronosyltransferases (UGTs) normally found in other species. In particular, UGT1A6 was found to be a pseudogene in cats and related Felid species (such as ocelots and pumas) suggesting that these enzymes may have been present in a common ancestral cat species, but are now defunct perhaps through loss of selective evolutionary pressures maintaining gene fidelity. More recent studies are attempting to substantiate this hypothesis by sequencing the UGT genes in phylogenetically related Felid species. Other related studies are investigating a possible role for deficient glucuronidation of dietary soy isoflavones in the etiopathogenesis of feline toxic thyroid nodular hyperplasia (funded by Ralston-Purina), as well as identifying the molecular basis for deficient metabolism of certain anesthetic agents in Greyhound dogs compared with other dog breeds.
In 2000, Dr Court completed the PhD degree program and subsequently joined the Pharmacology Department at Tufts as a faculty member and founding director of the Comparative and Molecular Pharmacogenetics Laboratory. The most recent work in this laboratory has concentrated on identifying the molecular pharmacogenetic determinants of interindividual variability in the functioning of drug metabolizing enzymes (primarily UGT1A6 and UGT2B15, as well as cytochrome P450 2B6) in people. These enzymes are of particular relevance to the metabolism and possible adverse side effects of drugs including acetaminophen, oxazepam, lorazepam, bupropion, and propofol. This work is currrently supported by the Pharmacogenetics Program at the National Institute for General Medical Sciences (NIH).
Dr Soundararajan Krishnaswamy, PhD: Dr. Soundararajan worked on production and physicochemical characterization of microbial exopolysaccharides for his PhD in the Department of Microbiology, Central Food Technological Research Institute, Mysore, India, from 1989-1995. In the study, two bacterial strains secreting highly viscous polysaccharides were isolated. A two-stage fermentation process, with only growth and multiplication of the bacteria occurring in a medium limiting in carbon and further production of the polysaccharide occurring in another medium limiting in nitrogen using the cells harvested in the first stage, was developed. A conformational change occurring above 75ºC caused the melting of the viscous polysaccharide fermentation broth and a method to filter the broth at high temperature was developed. The thermogellable microbial polysaccharide has potential applications as a thickening agent in foods and in the preparation of microbial media. Also, clarification of the viscous fermentation broth was achieved using a cell wall lytic protease excreted by a local soil isolate of a bacterium. A ß-glucanase, secreted upon the induction of a local isolate of a bacterium by the above polysaccharide, lysed the polysaccharide yielding octasaccharide units useful for further characterization. The protease and the glucanase were purified and characterized.
As a Post Doctoral Fellow in the Indian Institute of Science, Bangalore, India, he purified cytochrome P450 from the plant Catharanthus roseus in an attempt to study the role of cytochrome P450 in the biosynthetic metabolism of the antimetastatic compounds, vincristine and vinblastine. His other works include the isolation of a mannose-specific lectin from Dolichos lab lab seeds and attempts at manually sequencing the component peptides of the lectin, carried out in the Department of Biochemistry, Central Food Technological Research Institute, Mysore. During the period from Sep, 1996 up to March 2001 he served as lecturer in various Pharmacy, and Arts and Science colleges in the state of Tamilnadu, India.
Since April 2001 he has been working as a Postdoctoral Fellow, in the Department of Pharmacology, Tufts Health Science Campus, Boston, under the mentorship of Dr.Michael Court on polymorphisms of UGT enzymes in humans.
Comparative and Molecular Pharmacogenomics Laboratory
Department of Veterinary Clinical Sciences,
Washington State University College of Veterinary Medicine
100 Grimes Way, Pullman, WA 99163, USA.
Phone: 509-335-0817; Fax: 509-335-0880
Comments or problems please send email to: firstname.lastname@example.org
Last update: 10 October, 2012
Comparative and Molecular Pharmacogenomics
IMPORTANT - This laboratory has recently relocated to Washington State University in Pullman, WA.