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  Subhrangsu S. Mandal    

Phone: 817-272-3804    FAX: 817-272-3808     E-mail: smandal@uta.edu     Office: 349 CPB     Personal Page

Research interests:

Histone modification, Gene regulation, Estrogen signaling, Epigenetics and Cancer

The transcription (the process of copying DNA into RNA) and gene expression are highly complex and tightly regulated process that maintains the normal healthy status of cells. The goal of my laboratory is to understand the molecular mechanism by which genes are transcribed and regulated in healthy human cells and how genes are miss-regulated in human diseases such as in cancer and cardiovascular disease?

Post-translational modifications of nuclear histone proteins are critical in gene activation and silencing. We are interested in understanding the functions of a set of histone methyl-transferases (HMTs) that specifically methylate histone H3 at lysine 4 (H3K4) and play critical roles in gene activation and epigenetics.  Human encodes several H3K4 specific HMTs such as MLL1 (Mixed Lineage Leukemia 1), MLL2, MLL3, etc. MLLs are often rearranged in myeloid and lymphoid leukemias in both children and in adults. Our recent studies demonstrated that MLLs play critical roles in Hox gene expression, cell cycle regulation and are required for survival and maintenance of cancer cells. We also found that MLLs are essential for trans-activation of estrogen responsive genes indicating their critical roles in hormone signaling.

Using various biochemical techniques, cell cultures and mouse models, we aim to understand how MLL family of histone methylases regulates gene expression, hormone signaling and cancer in human.

Specifically, we study:
A.     Epigenetics: Functions of MLL histone methylases in Hox gene expression and cell cycle regulation.
B.     Molecular endocrinology: MLL histone methylases in estrogen signaling, blood cholesterol and cancer.
C.     Gene therapy: Develop novel targeted gene therapy (cell culture and mice model).
D.     Drug Development: Screen small molecules, metal-complexes in apoptosis assay to develop novel drugs
        (cell culture and mice model).

Recent Studies from our laboratory

Selected Publications:

Ansari K.I., and Mandal S.S. "Histone methylase MLL1 is critical for the cell cycle progression and maintenance of cancer cells," submitted 2009.

Ansari K.I., Kasiri S., Hussain, I. Reddy B.M and Mandal S.S. "MLL histone methylases play critical role in regulation HDLR-SRB1 and blood cholesterol," submitted 2009.

Ansari K.I., Grant, J.D., Kasiri S., Woldemariam G.A., Shrestha B., and Mandal SS. "Mn(III)-salen induce tumor cell apoptosis in MCF7 cells," J. Inorg. Biochem. 2009, in press.

Mishra B.P., Ansari K.I. and Mandal S.S. "Dynamic association of MLL1, H3K4 trimethylation with chromatin and Hox gene expression during cell cycle," FEBS J. 2009, in press.

Ansari K.I., Grant J.D., Woldemariam G.A. Kasiri S., and Mandal SS. "Iron(III)-salen complexes with less DNA cleavage activity exhibit more efficient apoptosis in MCF7 cells," Org. Biomol. Chem. 2009, 7, 926-32.

Ansari K.I., Mishra, B.M., and Mandal S.S. "MLL histone methylases in gene expression, hormone signaling and cell cycle," Review Front. Biosci. 2009, 14, 3483-95.

Osugi M.E., Zanoni M.V.B., Chenthamarakshan C.R., Tacconi N.R., Woldemariam G.A., Mandal S.S. and Rajeshwar K. "Toxicity assessment and degradation of disperse azo dyes by photoelectrocatalytic oxidation on Ti/TiO₂ nano-tubular array electrodes," J. Adv. Oxid. Technol. 2008, 11, 425-43.

Ansari K.I., Mishra B.M., and Mandal S.S. "Human CpG Binding Protein Interacts with  MLL1, MLL2 and hSet1 and Regulates Hox Gene Expression," Biochim. Biophys. Acta 2008, 1779, 66-73.

Woldemariam G.A. and Mandal S.S. "Iron(III)-salen Damages DNA and Induces Apoptosis in  Human Cell via Mitochondrial Pathway," J. Inorg. Biochem. 2008, 102(4), 740-7.

Mazloom A.R., Basu K., Mandal S.S., Sorourian M., Sajal K., and Das S.K. "DNA Sites Buried in Nucleosome Become Accessible at Room Temperature: A Discrete-Event-Simulation Based Modeling Approach," ISBRA 2007, 601-614.

Pavri R., Zhu B., Li G., Trojer P., Mandal S.S, Shilatifard A., and Reinberg D. "Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase, II," Cell 2006, 125(4), 703-17.

Zhu B., Zheng Y., Pham AD., Mandal S.S., Erdjument-Bromade H., Tempst P., and Reinberg D. "Mono-Ubiquitination of Human Histone H2B: The Factors Involved and their Roles in HOX Gene Regulation," Mol. Cell. 2005, 20, 601-11.

Zhu B, Mandal S.S, Pham A.D, Zheng Y, Erdjument-Bromage H, Batra SK, Tempst P, Reinberg D. "The human PAF complex coordinates transcription with events downstream of RNA synthesis," Genes Dev. 2005, 19, 1668-73.

Mandal S.S., Chun C., Wada T., Handa H., Shatkin A. and Reinberg D. "Functional interactions between mRNA capping enzyme and factors that positively and negatively regulate transcription during promoter escape," Proc. Natl. Acad. Sci. (USA) 2004, 101, 7572-77.

Mandal S. S., Sims R. J. and Reinberg D.  Review article on "Recent highlights in RNAP II mediated transcription," Curr. Opin. Cell Biol. 2004, 16, 263-71.

Endou M., Hasegawa J., Watanabe H., Kim D., Inukai N., Narita T., Shima D., Yamada T., Furuya A., Sato H., Hasegawa M., Yamaguchi Y., Mandal S. S., Reinberg D., Wada T. and Handa H. "Human SPT6 stimulates transcription elongation by RNA polymerase II in vitro," Mol. Cell. Biol. 2004, 24, 3324-36.

Mandal S. S., Cho H., Kim S., Cabane K. and Reinberg D. "FCP1, a phosphatase specific for the heptapeptide repeat of the largest subunit of RNA polymerase II, stimulates transcription elongation," Mol. Cell. Biol. 2002, 22, 7543-52.

Mandal S. S., Silva E. F. and Reha-Krantz, L. J. "Using 2-aminopurine fluorescence to detect base unstacking in the template strand during nucleotide incorporation by the bacteriophage T4 DNA polymerase," Biochemistry 2002, 41(13), 4399-4406.

Bhattacharya S. and Mandal SS. "Evidence of interlipidic ion pairing in anion induced DNA release from the cationic amphiphile-DNA complexes. Mechanistic implication in transfection," Biochemistry 1998, 37, 7764-7777.

Mandal S.S., Varshney U. and Bhattacharya S. "Role of central metal-ion and ligand charge in the DNA binding and modification by metallo-Salen complexes," Biocojugate Chem. 1997, 8, 798-812.

Research Funding:  Texas Advanced Research Program,  American Heart Association,  National Science Foundation

Department of Chemistry and Biochemistry
The University of Texas at Arlington
Arlington, Texas 76019-0065, USA
Phone: 817-272-3171 | Fax: 817-272-3808
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