Lalitha Nagarajan, Ph.D.
Present Title & Affiliation
Associate Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX
Factors that govern normal hematopoietic differentiation are targets of activation or inactivation in hematopoietic malignancies. Thus, aberrations in blood cell maturation due to an altered state of transcriptional regulation drive genetic and epigenetic reprogramming during malignant transformation. Initial clues on the critical genes came from non-random chromosomal changes associated with leukemia and lymphoma.
My laboratory cloned a candidate leukemia suppressor gene SSBP2 (sequence specific single stranded DNA binding protein 2) from a region of loss in human chromosome 5 in human acute myelogenous leukemia. SSBP2 encodes a transcriptional cofactor. SSBP2 containing transcriptional complexes regulate differentiation of hematopoietic and several other lineages. Normal differentiation program is compromised in the absence of SSBP2. More importantly, our recent studies establish the in vivo tumor suppressor function of Ssbp2. Mice with targeted disruption of Ssbp2 are predisposed to B cell lymphomas and carcinomas. Additionally, SSBP2 is also targeted by adenoviral oncoprotein E1B55K, implicating a broader tumor suppressor function for this gene. Thus aberrations of the Ssbp2 pathway appear to be novel genetic mechanisms in several malignancies. Elucidation of alterations in this pathway may lead to novel therapeutic targets
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