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 became Co-Leader of the University of Maryland Marlene and Stewart Greenebaum Cancer Center Experimental Therapeutics Program in July 2014. She 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.
Our laboratory also served as the reference laboratory for acute leukemia multidrug resistance studies in the cancer cooperative group Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology.
Subsequent work has focused on the role of the serine/threonine kinase Pim-1 in regulating drug resistance proteins. Pim-1 was 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 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 the role of Pim-1 kinase in acute myeloid leukemia with fms-like tyrosine kinase-3 receptor internal tandem duplication (FLT3-ITD) mutations, which are present in acute myeloid leukemia (AML) cells in approximately 30% of patients and are associated with adverse treatment outcomes. We have demonstrated that Pim kinase inhibitors, which are entering clinical trials, sensitize FLT3-ITD AML cells to FLT3 inhibitors and to chemotherapy drugs by diverse mechanisms. We are working on preclinical development of these novel therapeutic approaches to this common and unfavorable AML subtype.
Work in our laboratory has been supported by the National Cancer Institute and by Leukemia and Lymphoma Translational Research Program awards, and is currently supported by a Veterans Administration Merit Review award.
Lab Techniques and Equipment: