The cells in the human body are constantly trying to overcome damage to their DNA that results from both exogenous (tobacco smoke, alcohol) and endogenous sources (Reactive aldehydes, ROS) of stress, to ensure normal cellular function. Dysregulation of critical cellular processes, such as DNA replication, repair or transcription, can lead to chromosomal aberrations that lead to malignancies and other debilitating diseases. Research in our lab largely focuses on elucidating the molecular mechanisms that underlie the pathogenesis of cancer-predisposition syndromes and hematological malignancies. In particular, we are exploring the contribution of defective replication, transcription and repair to genomic instability in disorders like Fanconi anemia and Adult T-cell leukemia/lymphoma. In addition to our studies on determining the molecular basis of cancer-predisposition, we are also interested in understanding the primary mechanisms underlying hematopoietic stem cell exhaustion/attrition and bone marrow failure in Fanconi anemia using a human stem cell model for FA. We are employing a unique and specialized set of tools, which include our locus-specific single molecule assay to study DNA replication, cytogenetics, and genomics, to test our hypotheses.
