Maria R. Baer, M.D. joined the University of Maryland Marlene and Stewart Greenebaum Cancer Center as Director of Hematologic Malignancies in April, 2007, and is Professor of Medicine and Professor of Molecular Medicine, University of Maryland School of Medicine. She previously served as Chief of the Leukemia Section of Roswell Park Cancer Institute and Professor of Medicine and Associate Professor of Molecular Pharmacology and Cancer Therapeutics at the University at Buffalo School of Medicine and Biomedical Sciences in Buffalo, New York. Dr. Baer graduated magna cum laude from Harvard University and earned her medical degree from the Johns Hopkins University School of Medicine. She completed her residency in Medicine and fellowship in Hematology and was a National Research Service trainee at Vanderbilt University. She has conducted and participated in numerous clinical trials in leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Her laboratory focuses on mechanisms of drug resistance in leukemia cells.
Work in Dr. Baer's laboratory focuses on focuses on mechanisms of drug resistance in leukemia cells and strategies for overcoming them.
In previous work, we have studied expression and function of ATP-binding cassette (ABC) proteins associated with multi-drug resistance in leukemia cells, and have characterized inhibitors of these drug-resistance proteins and novel chemotherapeutic agents that are not susceptible to these resistance mechanisms.
Recent work has focused on the role of the serine/threonine kinase Pim-1 in regulating drug resistance proteins. Pim-1 has been found to phosphorylate the multidrug resistance-associated ABC proteins P-glycoprotein (Pgp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) and to enable their translocation to the cell surface, where they function as cellular drug efflux pumps. We recently demonstrated that Pim-1 phosphorylates Pgp in its core-glycosylated form and protects it from both proteasomal and proteolytic degradation, thereby stabilizing it and enabling its glycosylation and cell surface translocation. Current work focuses on further defining the effect of Pim-1 phosphorylation on BCRP expression and function.
We have also demonstrated that inhibition of Pim-1 kinase increases cytotoxicity of Pgp and/or BCRP substrate chemotherapy drugs, but not non-substrate drugs, in cells overexpressing these proteins, but not in dug-sensitive cells. We are determing whether inhibiting Pim-1 kinase enhances the cytotoxicity of chemotherapy in leukemia stem cells, using an in vivo transplant model. This work is supported by a Leukemia and Lymphoma Translational Research Program grant,
Our laboratory has also served as the reference laboratory for acute leukemia multidrug resistance studies in the cancer cooperative group Cancer and Leukemia Group B. In a collaborative study funded by an NIH grant, polymorphisms of the genes encoding the ABC proteins Pgp, BCRP and multidrug resistance protein-1 (MRP1) are being correlated with expression and function of these proteins in pretreatment AML cells from patients treated on Cancer and Leukemia Group B AML clinical trials, and with treatment outcome.
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