Associate Research Fellow
Compound Safety Prediction, Chemistry, Global R&D, Groton, CT
Collaboration
Lisa Tarantino, Ph.D.
Assistant Professor,
Department of Psychiatry
UNC School of Medicine
Genetic Medicine Building, CB 7361
Email: lisat@med.unc.edu
Ph: 919-843-7292
Education
Lisa Tarantino is an assistant professor in the School of Medicine, Department of Psychiatry. Dr. Tarantino received her PhD in Genetics from The Pennsylvania State University. After a postdoc at The University of Pennsylvania, Dr. Tarantino moved to the Genomics Institute of the Novartis Research Foundation (GNF) where she was both a Group Leader and Staff Scientist. Dr. Tarantino arrived at UNC in November 2007.
Research Interest
Dr. Tarantino’s interests and the focus of her research has always centered on the role of genetics and the environment on animal behavior, specifically in mouse models. The techniques she uses to address these problems have changed and evolved over the years as technology has advanced. Techniques in her lab include quantitative trait locus (QTL) mapping, haplotype association mapping and the use of a chemical mutagen, ethylnitrosourea (ENU), to induce random point mutations in mice. She uses these techniques to study animal behaviors that model anxiety, depression and addiction. Most recently, Dr. Tarantino was recently awarded ARRA funding to study the role of both genetics and pharmacokinetics in initial sensitivity to cocaine in inbred strains of mice. She is also part of a recently funded NHGRI Center of Excellence in Genomic Studies to examine gene by environment interactions in the development of anxiety, depression and stress-related behaviors in the Collaborative Cross mice. She is also the principal investigator on an R01 to identify the genetic mutation in an ENU-induced mutant that shows increased sensitivity to both the stimulating and reinforcing effects of cocaine as well as abnormal HPA response to stress. Her lab has also received a grant from the Foundation of Hope to study anxiety and depression-related behaviors in inbred strains of mice that have undergone ovariectomy.
Howard McLeod PharmD
Fred Eshelman Distinguished Professor
Division: Pharmacotherapy and Experimental Therapeutics
UNC Eshelman School of Pharmacy
CB #7361
Genetic Medicine Building, Room 1094
Chapel Hill , NC 27599-7360
Email: hmcleod@unc.edu, (919) 966-0512
Biography:
Howard McLeod, PharmD, is Fred Eshelman Distinguished Professor of Pharmacogenomics and Individualized Therapy at the UNC Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill and the director of the UNC Institute for Pharmacogenomics and Individualized Therapy. Dr McLeod holds additional appointments in the UNC School of Medicine and the Lineberger Cancer Center.
Dr. McLeod is the principal investigator for the CREATE Pharmacogenetics Research Network, a member of the NIH funded Pharmacogenetics Research Network, and is a member of the FDA Committee on Clinical Pharmacology. He directs the Pharmacogenetics for Every Nation Initiative that aims to help developing countries use genetic information to improve National Drug Formulary decisions. McLeod has published more than 350 peer-reviewed papers on pharmacogenomics, applied therapeutics, or clinical pharmacology and continues to work to integrate genetics principles into clinical practice to advance individualized medicine.
McLeod completed research fellowship training in cancer pharmacology at St. Jude Children’s Research Hospital in Memphis and at the University of Glasgow in Scotland before becoming the director of the clinical pharmacology program at the Beatson Cancer Centre in Glasgow. He then became a senior lecturer in medicine and director of laboratory research for the oncology unit at the University of Aberdeen in Scotland. McLeod returned to the United States in 2000 to accept a position at Washington University in St. Louis, Missouri, where he was a professor in the Departments of Medicine, Pharmacology and Molecular Biology, and Genetics and director of the Siteman Cancer Center Pharmacology Core.
Departments:Pharmacotherapy and Experimental Therapeutics:
Research Interest:
When a drug goes through clinical trials, its effectiveness and side effects are determined based on a large population. However, that information only tells individual patients what is possible. It does not tell them what their own experience is likely to be. There are dramatic differences among people in their reaction to a particular medicine.
“In cancer and almost every other area of medicine, there are multiple drugs that work,” says Howard McLeod, who joined UNC-Chapel Hill in 2006 as the Fred Eshelman Distinguished Professor of Pharmacy and professor of medicine. “But none of them work on more than half the patients. So when prescribers are faced with choosing what medicine to give a person, they often go with the drug they know best. And because there is often no way to know with great certainty how the drug may work in that individual, it may not be the one that will benefit the patient the most.”
McLeod, PharmD, wants to help physicians get it right the first time when they select a medicine to treat cancer and other illnesses. He is heading a new research institute at the School of Pharmacy that will find ways to match medicines to the unique makeup of the people needing them.
McLeod, an internationally recognized expert in the pharmacogenomic analysis of cancer treatments, is the director of the new UNC Institute for Pharmacogenomics and Individualized Therapy. The institute will work to create effective therapy and precise treatment options for individual patients suffering from a wide range of conditions. Initial efforts will focus on cancer therapy with planned expansion into cardiovascular disease, psychiatric disorders, and global health.
The McLeod laboratory uses genetic tools to perform in vitro, ex vivo, and clinical evaluations to discover, validate, and apply molecular predictors of therapeutic outcome. This includes candidate-gene and genome-wide human association studies, computational and functional characterization of newly discovered genetic variants, and the use of multiple strains of inbred mice to provide a broadbased approach toward understanding inherited sources of variability in drug effects.With the draft of the human genome completed in 2001 and experimental organisms such as the mouse and rat either completed or near completion, a large volume of sequence information has been generated with only limited understanding of the contents. A functional genomics approach is needed to bridge the gap between the DNA sequence information itself, the genes and regulatory information it contains, and functional roles within the cell.
William C. Zamboni PharmD, PhD
Associate Professor, DPET; Associate Member, Lineberger Comprehensive Cancer Center; Director, GLP Analytical Facility, UNC Eshelman School of Pharmacy and UNC Lineberger Comprehensive Cancer Center
Division: Pharmacotherapy and Experimental Therapeutics
120 Mason Farm RD
1013 Genetic Medicine Building
CB 7360
Chapel Hill , NC 27599-7360 Work: (919) 843-6665
Associate Professor, DPET; Associate Member, Education:
Director, GLP Analytical Facility Lineberger Comprehensive Cancer Center
UNC Eshelman School of Pharmacy and UNC Lineberger Comprehensive Cancer Center
Division: Pharmacotherapy and Experimental Therapeutics
Education
- 2001 - 2005: Doctor of Philosophy, Clinical Pharmaceutical Scientist Program, Dept. of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA. Dissertation was entitled “Preclinical and Clinical Pharmacologic Studies of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite”.
- 1995 -1997: Research Fellowship, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN.
- 1994 - 1995: Oncology Pharmacy Residency, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD.
- 1992 - 1994: Doctor of Pharmacy, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
- 1988 - 1992: Bachelor of Science in Pharmacy, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
Biography:
Research Interests:
My research program is part of the Division of Pharmacotherapy and Experimental Therapeutics in the School of Pharmacy at the University of North Carolina (UNC) and the UNC Lineberger Comprehensive Cancer Center. I have been involved in translational studies of anticancer agents for several years. My research interests focus on the application of pharmacokinetic, pharmacodynamic, and pharmacogenetic principles in the optimization of the chemotherapeutic treatment of cancer. Information obtained from preclinical and clinical translational studies can greatly add to the understanding of the pharmacology of anticancer agents, permit individualization of chemotherapeutic treatment based on pharmacokinetic, pharmacodynamic, and pharmacogenetic principles, and allow for the rational design of therapeutic regimens.
A second focus of my research is on the development of liposomal and nanoparticle anticancer and evaluating the relationship between the disposition of these agents and the reticuloendothelial system. As part of these studies I have used microdialysis to evaluate the tumor extracellular fluid disposition of anticancer agents and factors affecting the delivery and removal of anticancer agents. I have also developed methods and technologies to differentiate between the inactive-encapsulate and active-released forms of the drugs and are evaluating potential phenotypic probes for the pharmacokinetic and pharmacodynamic disposition of liposomal and nanoparticles. The clinical relevance of studies is underscored by the need to treat solid tumors with anticancer agents that have high tumor penetration, develop methods to increase the tumor delivery of liposomal and nanoparticle agents, and generate administration schedules to enhance selective tumor uptake.
Russell Thomas, Ph.D.
Senior Investigator and Director, Genomic Biology and Bioinformatics
The Hamner Institute
Education
B.A., chemistry, Tabor College, Hillsboro, Kansas, 1991.
M.S., radioecology, Colorado State University, Fort Collins, Colorado, 1993.
Ph.D., toxicology, Colorado State University, Fort Collins, Colorado, 1998.
Postdoctoral training, McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin, 1998-2000.
Research
With the draft of the human genome completed in 2001 and experimental organisms such as the mouse and rat either completed or near completion, a large volume of sequence information has been generated with only limited understanding of the contents. A functional genomics approach is needed to bridge the gap between the DNA sequence information itself, the genes and regulatory information it contains, and functional roles within the cell.
In toxicology, the application of genomics and associated technology was initially forecast to lead to the rapid identification and mechanistic understanding of physical and chemical agents that result in adverse human or environmental end points. These forecasts have created a wave of excitement within the toxicology community, with an increasing number of researchers applying genomic tools such as microarrays to various research projects. However, with a few notable exceptions, the increasing application of these tools has not resulted in a substantial increase in the mechanistic understanding of how various chemical and physical agents act on a system or improved our ability to predict how these systems behave at low doses. The missing components are a basic understanding of the cause-and-effect relationship contained within these lists of genes and the underlying logic of the signaling network involved in producing the toxicological effect at environmentally relevant doses.
To delineate the signaling network involved in the toxicological effect and the cause-and-effect relationships among the altered transcripts, new approaches specifically designed to address the functional aspects of these genomic alterations are necessary. Notably, no single technology can be relied on to accomplish these goals. A functional genomics approach that combines a variety of disciplines and utilizes broad-coverage experimental and computational methods holds promise for addressing these needs. The research program in my laboratory is focused in three primary areas.
Functional genomic screens to dissect upstream cellular signaling pathways:
Dissecting the upstream cellular signaling pathway is important to understand the potential targets of toxicity, identify key nodal points in the signaling pathway, and identify potential cross-talk among pathways known to be involved in other biological end points (e.g., development or inflammation).
Functional genomic screens to identify genes involved in susceptibility:
Applying gain-of-function and loss-of-function screens in cells exposed to a marginally toxic or subtoxic dose can identify potential modifiers of susceptibility. For example, some people may express more or less of a certain gene than others in the general population. The reasons for this difference in expression are numerous and can include nutritional state, physiological state (e.g., inflammation), and genetic polymorphisms.
A combination of gene expression analysis and functional genomic tools to map downstream gene expression trees:
Identifying the upstream cellular signaling pathway is only part of the overall picture. The event initiated by the chemical may not necessarily be directly responsible for the toxic end point but instead may be driven by downstream (i.e., secondary and tertiary) alterations in gene expression. In other words, what branch on the tree representing the time-course changes in gene expression following exposure to a toxic chemical is responsible? In addition, the specific gene expression tree can vary significantly among species, resulting in cross-species differences in toxicity. For example, what if the gene upstream of the node responsible for toxicity is missing or has evolutionarily acquired a different function in humans but not in rats or mice? The ultimate biological response would also be different. Comparisons of these gene expression trees are important both for understanding the mechanism of toxicity and for the cross-species scaling of the toxic end point.
Mathew Pletcher ,Ph.D.
Mathew Pletcher received a B.S. in Biology from Duquesne University and a Ph.D. in Human Genetics from Johns Hopkins School of Medicine. He has held a post-doctoral position at the Genomics Institute of the Novartis Research Foundation before joining the Scripps Research Institute as an Assistant Professor in Department of Molecular Therapeutics and the Director of the Genomics Core Facility. His work included the establishment of the first haplotype map of the inbred mouse strains and development of methodologies for conducting genomics-based investigations using panel of inbred strains of mice. From there, he came to Pfizer to found the Non-clinical Pharmacogenomics laboratory within Investigative Toxicology. He now heads the Mechanistic Toxicology group of the Compound Safety Prediction.
Professional Affiliations
Mammalian Genome Society, Society of Toxicology
Education
B.S. - Biology, Duquesne Univeristy
PhD - Human Genetics, Johns Hopkins School of Medicine
Published Articles
27 peer-reviewed articles and 2 book chapters including;
Miller, B.H., Schultz, L.E., Gulati, A., Cameron, M.D., Pletcher, M.T. (2008) Genetic regulation of behavioral and neuronal responses to fluoxetine. Neuropsychopharmacology 33, 1312-22.
Hayes, K.R., Young, B.M., Pletcher, M.T. (2009) Expression Quantitative Trait Loci mapping identifies new genetic models of glutathione S-transferase variation. Drug Metabolism and Disposition 37, 1269-76.
Pletcher, M.T., Cook, J.C., and Tassinari, M.S. (in press) The Influence of Genetics, Nutrition, and Pharmaceuticals on Developmental Outcome, in Comprehensive Toxicology (Knudsen, T.B. and Daston, G.P. eds), Elsevier, Kidlington, United Kingdom.
