Jatinder Lamba, Ph.D.
Department of Experimental and Clinical Pharmacology
College of Pharmacy
Institute of Human Genetics
University of Minnesota
14-271 Moos Tower
420 Delaware St. S.E., MMC 206
Minneapolis, MN 55455
B.Sc., 1992 Panjab University, Chandigarh, India (Zoology, Botany, Chemistry)
M.Sc., 1994 Postgraduate Institute of Medical Education and Research, Chandigarh, India (Biochemistry)
Ph.D., 2000 Postgraduate Institute of Medical Education and Research, Chandigarh, India “Pharmacogenetics of CYP2C19 in North Indians”
2000- 2006, Postdoctoral Research Associate, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
2006- 2008, Research Associate, Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
July 2008 – Present, Assistant professor, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota
The overall objective and goal of my research work is to identify comprehensive panels of potentially functional and clinically relevant genetic polymorphisms in pharmacokinetic (ADME) and pharmacodynamic pathways important for the treatment in childhood leukemia. My long term goal is to move pharmacogenetic testing into the clinical setting to improve safety and efficacy of drug therapy. To accomplish this, we have developed a focused, productive, and independent program in pharmacogenomics research. My research spans preclinical basic research comprising the discovery phase to translational/clinical phase in patient populations. The former focuses on use of cell lines from different ethnic groups that are part of international HAPMAP project as a model for pharmacogenomic discovery. My lab has established 180 HAPMAP cell lines in my lab that are also available to other investigators for collaborative projects. The translational phase involves patient oriented research to determine the clinical impact of basic research/pharmacogenomic findings. We have successful collaborations with clinical investigators in hematology-oncology at St. Jude Children’s Research Hospital, Masonic Cancer Center at UMN, Fred-Hutchinson Cancer Center, Mayo Clinic as well as with multiple cooperative groups such as Children’s Oncology Group (COG) and Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL).
Research Focus areas:
Pharmacogenomics of Anticancer Drugs: Includes pathway directed pharmacogenomics approach to study inter-patient variation in drug response to chemotherapeutic agents as nucleoside analogs, platinating agents (funded by Minnesota state partnership funds) monoclonal antibodies etc.
One of the main ongoing projects funded by NCI is focused on pharmacogenomics of cytarabine in childhood leukemia. Cytarabine is mainstay of AML chemotherapy, it itiself is inactive and requires activationinside the cell by mulitple phosphorylation steps.An uptake transporter hENT1 is crucial for ara-C uptake into the cell where it is, ara-C phosphorylation by deoxycytidine kinase (DCK) is the rate-limiting step in ara-C activation . The resulting ara-C monophosphate (ara-CMP) is then further phosphorylated by pyrimidine kinases to the active 5’-triphosphate derivative, ara-CTP. Conversely, the enzyme 5’-nucleotidase (NT5C2) can dephosphorylate ara-CMP back to ara-C, while ara-C and ara-CMP can both be converted into the inactive forms, ara-U or ara-UMP, by the action of the enzymes cytidine deaminase (CDA) and deoxycytidylate deaminase (DCTD), respectively. DNA incorporation of ara-CTP in place of deoxycytidine triphosphate (dCTP) results in chain termination, blocking DNA and RNA synthesis and causing leukemic cell death, which in turn is associated with therapeutic response of ara-C. Thus genetic variation in key genes in the ara-C metabolic pathway can influence inter-patient variability in intracellular ara-CTP concentrations and sensitivity to ara-C. Our lab This NCI funded project focuses on understanding genetic variants in the key candidate genes involved in the metabolic activation of ara-C, as well as pharmacodynamic targets of ara-C, providing an opportunity to identify patients at increased risk of adverse reactions or decreased likelihood of response, based upon their genetic profile, which in future could help in dose optimization to reduce drug toxicity without compromising efficacy. The pharmacogenetic studies on ara-C would also be equally applicable to other nucleoside analogs such as gemcitabine, decitabine, clofarabine, etc. that are metabolized by the same pathway.
Pharmacogenomics of drug metabolism: This collaborative project with Dr. Vishal Lamba involves understanding factors contributing to inter-individual differences in drug metabolism.
Pathway Driven Pharmacogenomics, University of Minnesota Alliance (PUMA)
PUMA is a coordinated effort by a group of University of Minnesota researchers with expertise in multiple disciplines to advance understanding of the role played by pharmacogenomics in explaining the inter-individual variation observed in therapeutic response and outcome and treatment related toxicity. The long term goal is to move pharmacogenetic testing into the clinical setting to improve safety and efficacy of drug therapy. PUMA is an affiliate member of the national organization Pharmacogenetics Research Network (PGRN).