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Experts in Genetics
Sanjay Gupta Aimée M. Dudley David Buchanan Drena Dobbs Karin S Dorman Dr. Xun Gu Thomas Peterson IRFAN AHMAD ANSARI John Golin Jannice Friedman Vimla Aggarwal Andrea Rinaldi Carmen Argmann Eleanor Maine Albertini Alessandra Judith Greenberg Mark Clark John F. Hayes Ashok Kumar Roger I. Cue View More1. With a series of original experiments, our works on cellular and molecular mechanisms of arsenic trioxide (As2O3) in vitro and in vivo have been attracting worldwide interests. The related progresses have been published in PNAS, JNCI, BLOOD, Leukemia and others. 2. We reported recently that mild hypoxia and hypoxia mimetic agents cobalt chloride and desferrioxamine (DFO) can induce differentiation of human acute myeloid leukemic (AML) cellsin vitro and in vivo,acting via a hypoxia-inducible factor-1 alpha (HIF-1a), which interact physically with andincrease the transcriptional activity of CCAAT/enhancer binding protein alpha (C/EBPa), acritical factor for granulocytic differentiation. The related discoveries have been publishedin several journals such as Blood, Leukemia, Proteomics, Heamatologica, BBRC and Apoptosis. 3. We report that all-trans retinoic acid (ATRA) and PMA, effective differentiation-inducing agents of AML cells, can elevate phospholipid scramblase 1 (PLSCR1) expression by activated protein kinase Cd (PKCd). We also show that interferon-a induces expression of PLSCR1 through STAT1 requires sequential activation of PKCd & JNK. Decreasing PLSCR1 expression with small interfering RNA inhibits ATRA/PMA -induced differentiation. Taken together, these results suggest that as a protein induced upon PKCd activation, PLSCR1 is required for ATRA and PMA-triggered leukemic cell differentiation. The related discoveries have been publishedin Blood Oncogene and J Biol Chem. 4. As a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. We report that nanomolar concentrations of NSC606985, a rarely studied camptothecin analog, induces apoptosis in AML cells by NSC606985 by rapid induction of the proteolytic activation of PKCd with loss of mitochondrial transmembrane potential and caspase-3 activation. The following animal experiments showed its effectiveness in vivo to induce apoptosis and to elongate survival of leukemic mice. The related discoveries have been published in Blood an other journals. 5. We reported that AML1-ETO, a fusion protein of chromosome translocation (8;21) frequently occurred in AML, induced cell cycle arrest via upregulating connexin 43 expression and increased the sensitivity to intrinsic and extrinsic apoptosis. The related works have been published in Leukemia and J Cell Physiol.
Dr. Chen and his colleagues have been devoting efforts to investigate mechanisms of leukemogenesis and of leukemic cell differentiation and apoptosis, functional genomics of cancer, proteomics with the core of identifying leukemia-related interacting proteins, and the identification of leukemic drug targets in the treatment of induced differentiation.