Lori A. Pile
Lori A. Pile, Ph.D.
4111 BSB, 5047 Gullen Mall
Detroit, MI 48202
- Chromatin structure and function
- Regulation of gene express
- Histone modification in development and cell proliferation
Gene expression is regulated in part by the interactions of genomic DNA with the packaging histone proteins. Research in the Pile laboratory is directed toward understanding how genome packaging affects gene expression. Histones undergo a variety of modifications including acetylation, phosphorylation and methylation, which in turn affect the level of packaging. We are currently investigating how the SIN3 histone deacetylase complex functions to repress transcription at the epigenetic level. SIN3 is required for viability of multi-cellular organisms and mutations in components in the complex have been linked to defects in cell cycle progression. Current objectives of the lab are to understand regulatory pathways that affect SIN3 activity and to understand the consequences of SIN3 recruitment at target genes. We are taking a multi-pronged approach to address these questions in the model organism Drosophila melanogaster. We utilize a combination of biochemical, molecular and genetic techniques to understand the mechanism of SIN3 gene regulation. Data from these studies will help to elucidate the contribution of histone acetylation to signaling cascades that impact cellular decisions critical for proliferation, development and viability.
Liu M and Pile LA. The Transcriptional Corepressor SIN3 Directly Regulates Genes Involved in Methionine Catabolism and Affects Histone Methylation, Linking Epigenetics and Metabolism. J Biol Chem. 2016 Dec 27.
Chaubal A, Todi SV, and Pile LA. Inter-isoform-dependent Regulation of the Drosophila Master Transcriptional Regulator SIN3. J Biol Chem. 2016;291:11566-71.
Saha N, Liu M, Gajan A, and Pile LA. Genome-wide studies reveal novel and distinct biological pathways regulated by SIN3 isoforms. BMC Genomics. 2016;17:111.
Gajan A, Barnes VL, Liu M, Saha N and Pile LA. The histone demethylase dKDM5/LID interacts with the SIN3 histone deacetylase complex and shares functional similarities with SIN3. Epigenetics & Chromatin 2016;9:4.
Liu M, Barnes VL and Pile LA. Disruption of Methionine Metabolism in Drosophila melanogaster Impacts Histone Methylation and Results in Loss of Viability. G3 (Bethesda). 2015;6:121-32.
Holowatyj A, Yang ZQ and Pile LA. Histone lysine demethylases in Drosophila melanogaster. Fly (Austin). 2015;9:36-44.
Barnes VL, Bhat A, Unnikrishnan A, Heydari AR, Arking R, Pile LA. SIN3 is critical for stress resistance and modulates adult lifespan. Aging (Albany NY). 2014;6:645-60.
Education and Training:
PhD in Molecular Genetics, Biochemistry and Microbiology (1998): University of Cincinnati Medical School
Cancer Biology Courses Taught:
CB7220 Molecular Biology of Cancer Development