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Debu
Chakravarti, Ph.D.
Asst Professor, Dept of Pharmacology School of Medicine
810/833 BRBII/III
421 Curie Blvd Philadelphia 19104-6160
215-573-8470, Lab: 215-573-8471
Fax: 215-573-9004
Email: debu@pharm.med.upenn.edu
Click here for selected publications since Dr. Chakravarti's arrival at Penn
RESEARCH INTERESTS
Molecular mechanisms and regulations of steroid hormone and vitamin signaling;
Viral and cellular regulation of CBP/p300 coactivator function; Regulation
of histone modification and translating the "Histone Code; Identification
of novel regulators of transcriptionRESEARCH TECHNIQUES
Molecular and Cell Biology, mammalian cell based transfection and ChIP assays, siRNA, Biochemistry and protein purificationRESEARCH SUMMARY
Our laboratory studies (a) the molecular mechanisms of nuclear signal transduction by steroid hormone and vitamins and (b) roles and regulations of histone modifications in translating the "Histone Code" of gene expression. Members of the nuclear receptor superfamily mediate the actions of steroid hormones and vitamins by functioning as ligand regulated transcription factors. Recently we have demonstrated that coactivators and corepressor proteins modulate transcriptional regulatory properties of nuclear receptors. Alterations of receptor/hormone function as well as that of coactivator and corepressor proteins have been implicated in several diseases including developmental and neurological defects, cardiovascular diseases, diabetes, and leukemia.Described below are the present research interests in the laboratory:
1. Isolation and Characterization of Novel Components of the Receptor Signaling Complex: We are combining molecular (yeast two hybrid screens) biochemical (protein purification, and enzymatic assays), cell biological (transfection, immunohistochemistry, and confocal microscopy) approaches to identify and characterize new components of receptor coactivator, corepressor transcriptional signaling complexes.
2. Regulation of histone modifications and translating the "Histone Code": Histone modifications including acetylation, methylation and phosphorylation play important regulatory roles in gene expression. Using ChIP, transfection, reporter gene based assays coupled to biochemical assay -based preparative purification methods, and molecular cloning, we are identifying novel proteins (including INHAT) involved in regulating histone modifications and translating the "histone code" for gene expression. Interestingly, the INHAT subunits have been implicated in leukemia. We are also undertaking molecular and biochemical approaches utilizing ChIP, si-RNA, and Cell based transfection assays to understand the mechanisms underlying the above regulatory pathways and how viral and cellular proteins contribute to cell transformation and leukemia by altering hormone and other signaling pathways.
KEY WORDS:
Signal Transduction, Nuclear Receptors, Coactivators & Corepressors, LeukemiaHormone and vitamin signal transduction, Transcriptional regulation, Nuclear receptors, Coactivators & Corepressors, Histone modifications, and Implications in leukemia
