As part of the Institute of Pharmacogenomics and Individualized Therapy (IPIT), the Wiltshire lab is dedicated to linking genes and disease through the use of haplotype-associated mapping.  This is achieved by using data from gene expression studies, biomarker analysis and behavior phenotypes in various strains of mice and associated with the haplotype map (HapMap.)  Our major focus is on anxiety and depression and the drugs used to treat them.

Biography

Timothy  Wiltshire Ph.D.

Dr. Wiltshire’s current research focus centers on pre-clinical pharmacogenetics using mouse models.  Dr Wiltshire received a B.S. in Organic Chemistry from the University of Canterbury, New Zealand, and then went on to become certified as a High School teacher.  He taught High School for a number of years in New Zealand and then made a career change and came to the US to pursue a Ph.D.  He received his Ph.D in Biochemistry and Cell and Molecular Biology from the University of Tennessee and then went on to post-doctoral research positions at the Johns Hopkins School of Medicine and the University of Pennsylvania.  Dr. Wiltshire joined the Genomics Institute of the Novartis Research Foundation as a scientist and over 8 years became a Senior Research Investigator there.  The main direction of his research was mouse models of disease, genetics and genomics and a focus on developing resources, (SNPs, gene expression and genetic analysis methods) using inbred strains of mice.  The major theme of this work was to identify novel drug targets for the Novartis drug discovery pipeline.  

Dr .Wiltshire is now an Associate Professor in the Division of Pharmacotherapy and Experimental Therapeutics and an Associate Director for the Institute for Pharmacogenomics and Individualized Therapy. He also holds adjunct faculty positions in the Department of Genetics, UNC School of Medicine, and the Lineberger Comprehensive Cancer Center at UNC and is actively involved with several collaborations with the Hamner Health Sciences Institute.

Lab projects largely involve the use of a number of different inbred mouse lines that have been well characterized genetically.  There are 30 -40 mouse lines that are routinely used.  After phenotypes are measured in these mouse lines, haplotype association analysis can identify those regions of the genome that are associated with the phenotype.   Mostly these analyses result in a list of a few candidate genes which can be then tested to see if they are causally linked to the phenotype.  Current projects involve:  1) determining the effects of fluoxetine on behavioral phenotypes in the mouse.  Fluoxetine affects mouse behavioral phenotypes; but not for all strains of mice.  We are trying to identify a set of biomarkers that define which mouse strains will respond to treatment. 2) We have a cell-based high-content imaging screening platform developed to identify toxicity pathways for multiple drugs.  Here we use primary cell lines from the same genetically defined mouse lines to measure cell health status after drug treatments; again using this information to identify genes that are responsible for variability in drug responses. 3) We also have three projects underway to look at pharmacogenetic response to anti-cancer agents, in particular for oxaliplatin, docetaxol, and doxorubicin.  Oxaliplatin causes adverse drug responses of peripheral neuropathy, docetaxol causes neutropenia in some patients and doxorubicin resistance is an issue for hematologic cancers.  We aim to identify some genes which lead to additional understanding of these concerns.