Lurie Cancer Center Member
Janardan K Reddy, MD
Professor, Pathology; Feinberg School of Medicine
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Autopsy pathology, Liver and pancreatic pathology
Our current work focuses on the molecular mechanisms responsible for PPAR action. Transcription of specific genes initiated by transcription factors/nuclear receptors is a complex process and involves the participation of multiprotein complexes composed of transcription coactivators. Coactivators contain one or more highly conserved LXXLL (L, leucine; X, any amino acid) motif for direct interaction with AF-2 (activation function 2) region in nuclear receptor. Our laboratory cloned PBP, PRIP, PIMT, PRIC285 and PRIC320 using either yeast two-hybrid screening or by isolating receptor binding proteins and their identification by MALDI-TOF analysis. We are generating gene knockout mouse models to elucidate the role of these coactivators in the regulation of specific gene transcription. Our work demonstrated that the deletion of PBP, PRIP PIMT and PRIC320 genes in the mouse results in embryonic lethality, indicating that these are vital for development and they alter the function of many nuclear receptors and other transcription factors during critical developmental stages. Recent developments in the area of conditional targeted somatic mutagenesis have opened new avenues for analyzing the physiological functions of coactivator signaling in a variety of tissues and cell types during early development and in the adult.