The Department of Nutrition and Natural Product

Our main interest in the cancer drug discovery program revolves around cancer drug resistance, and in particular, in Ph+ leukemia. In general, Ph+ leukemia drug resistance to therapy might be due to mutations within BCR/ABL or associated with disease progression that is independent of BCR/ABL mutations. To overcome drug resistance caused by point mutations, specially the "gatekeeper" T315I mutation, we explored modulators of the Myristoyl Binding Pocket (MBP) within the BCR/ABL {Khamaisie et al., 2011; Najajreh et al., 2013} and combinations approaches utilizing AKIs with allosteric inhibitors {Khateb et al., 2012; Mian et al., 2012}. Currently, we are addressing residual disease, cell-adhesion mediated resistance, and disease progression of Ph+ leukemia which is independent of BCR/ABL mutations. Specifically, we are exploring the interaction between the Ph+ leukemic cells to the bone marrow microenvironment and studding the role of epithelial-mesenchymal transition (EMT) activators in mediating homing and adhesion to the bone marrow, mediated by affecting the expression of CD44, CD184, and N-cadherin that contribute to residual disease, stimulate drug resistance, and accelerate disease progression in most hematopoietic malignancies. Our long term goal is to get a better understanding of the role of EMT activators in the biology of Ph+ leukemia, especially in the regulation of bone marrow homing and adhesion of Ph positive leukemia cells which play a significant role in disease progression and drug resistance. Achieving our goals will be utilized to develop better diagnostic and therapeutic tools for Ph+ leukemia and potentially to other hematological malignancies.