Mohammad Azam, PhD
Title
Assistant Professor, Cancer Pathology Program of the Division of Experimental Hematology and the Division of Pathology
Appointment
Assistant Professor,University of Cincinnati College of Medicine, University of Cincinnati College of Medicine
Email
mohammad.azam@cchmc.org
Credentials
PhD: Jawaharlal Nehru University, India.
Post-doc: Whitehead Institute for Biomedical Research at MIT (2001-2003).
Instructor: Children’s Hospital of Boston and Harvard Medical School. (2006-2009).
Awards and Honors
Awarded Gold medal in MSc
Research
We are interested in understanding molecular basis of human cancers, especially hematopoietic malignancies. A detailed understanding of the development of these cancers should provide insights about the candidate genes and pathways involved in the pathogenesis of cancer and the development of novel therapeutic approaches. Our research group focuses on understanding the mechanisms of tyrosine kinase regulation, oncogene addiction and the development of cancer stem cells. Experimental approaches in our research are interdisciplinary, including chemical, biochemical, molecular, biophysical and in vivo mouse models.
Structure and function analysis of tyrosine kinases involved in the pathogenesis of leukemia: We are studying the structural basis of BCR/ABL, JAK2, PDGFRA, PDGFRB, c-KIT and EGFR kinase activation and how they initiate oncogenesis. We employ random mutagenesis and site directed mutagenesis to identify the critical regions in primary and tertiary structures that regulate kinase function.
Molecular basis of “oncogene addiction”: So for we do not know how an activated kinase activates the oncogenic machinery to make the cancer cell kinase dependent for survival. We are using expression analysis combined with genetic and chemical screens to identify candidates involved in these intricate pathways.
Modeling of human leukemia in mice using ES and patient derived iPS Cells. We are building tools for gene expression and gene knock-down in human ES and iPS cells to facilitate experimental and therapeutic studies in mice using human cells.
Publications, Most Recent
Azam, M., and Daley, GQ. Anticipating Clinical Resistance to Target-directed Agents: BCR-ABL an example. Molecular Diagnosis and Therapy. 2006;10(2):67-76.
Azam Mohammad , Nardi Valentina, William C. Shakespeare, Chester A. Metcalf III, Regine S. Bohacek, Yihan Wang, Raji Sundaramoorthi, Piotr Sliz, Darren R. Veach, William G. Bornmann, Bayard Clarkson, David C. Dalgarno, Tomi K. Sawyer, and George Q. Daley. Activity of dual SRC-ABL inhibitors highlights role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci USA- 2006. June 13; 103, 24: 9244-9249.
Raz T, Nardi V, Azam M, Cortes J, Daley GQ. Farnesyl transferase inhibitor resistance probed by target mutagenesis. Blood. 2007 Sep 15;110(6):2102-9.
Azam M, Seeliger M, Gray S, Kuriyan J, Daley GQ. Activation of tyrosine kinases by the mutation of gatekeeper residue. 2008: Nature Structural and Molecular Biology.
Azam M and Daley GQ. 2008: Cellular transformation and leukemia development by activated tyrosine kinases. Nature Protocols. 2008.
Nardi V, Azam M, Neverias O, Daley GQ. Immune-Mediated Protection AgainstBCR/ABL-Induced Leukemia: A Common Pathway Shared between IRF8/ICSBP and IFN alpha and beta. Blood. 2009.
Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, Shah SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan CG, Golub TR, Sorensen PH, Daley GQ. Lin28 promotes transformation and is associated with advanced human malignancies. Nature Genetics. 2009 May 31.
Azam M, Powers JT, Shakespeare W, Zhang X, dalgarno D, Sawyer TK, Clackson T And Daley GQ. AP24163 inhbits the gatekeeper mutant of BCR/ABL by disrupting hydrophobic spine and P-loop flexibility. Chemical Biology and Drug design. 2009 ( In Press).
Jianming Zhang, Francisco J. Adrián, Wolfgang Jahnke, Sandra W. Cowan Jacob, Allen G. Li, Roxana E. Iacob, Taebo Sim, John Powers, Christine Dierks, Fangxian Sun, Gui-Rong Guo, Qiang Ding, Barun Okram, Yongmun Choi, Amy Wojciechowski, Xianming Deng, Guoxun Liu, Gabriele Fendrich, Andre Strauss, Navratna Vajpai, Stephan Grzesiek, Tove Tuntland, Yi Liu, Badry Bursulaya, Mohammad Azam, Priscilla L. Yang, Paul W. Manley, John R. Engen, George Daley, Markus Warmuth, Nathanael S. Gray. Targeting wild-type and T315I Bcr-Abl by combining allosteric and ATP-site inhibitorsi.Nature, 2009 (in Press).
Presentations, Most Recent
Annual Meeting of AACR (2006). Activity of dual SRC/ABL inhibitors implicates the kinase dynamics in drug resistance.
CHI, meeting at Boston (2006). Screening against dual SRC/ABL inhibitors reveals the role of kinase dynamics in resistance.
Annual meeting of AACR (2007). Plenary session. A unified mechanism of kinase activation by mutation of the gatekeeper residue.
Pfizer technology center at Cambridge (2007). Imatinib resistance in Chronic Myeloid Leukemia: A paradigm for the drug resistant mechanisms in targeted therapy.
Annual Meeting of American Society of Hematology (2007). A common mechanism of yrosine kinase activation by mutation of the gatekeeper residue.
Annual Meeting of European Society of Hematology (2008). Mutagenesis to probe kinase function and drug resistance.
Department of Leukemia at MD Anderson Cancer Center (2008). Mechanisms of drug resistance in CML.
Memorial Sloan Kettering Cancer Center (2008). Tyrosine kinase inhibitor therapy in cancer: Promises and pitfalls.
Gen*NY*Sys at university of Albany (2008). Molecular mechanisms of drug resistance in CML.
Professional Organization Memberships
Special Interests
Leukemia
