ZIA CP010201-10571 (ZIA) | |||
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Title | LTG_Prokunina | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Prokunina, Ludmila | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $850,536 | Project Dates | 10/12/2010 - N/A |
Fiscal Year | 2012 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Bladder (30.0%) Breast (10.0%) Liver Cancer (30.0%) Prostate (30.0%) |
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Research Type | |||
Exogenous Factors in the Origin and Cause of Cancer Endogenous Factors in the Origin and Cause of Cancer |
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Abstract | |||
Recent genome-wide association studies (GWAS) have identified multiple common inherited genetic susceptibility factors that may play a role in a variety of human diseases and outcomes. The primary goal of my research is to identify the functional links between these genetic associations and molecular phenotypes. We use a wide range of methods including DNA sequencing and genotyping, RNA sequencing, statistical imputation, protein expression studies, DNA-protein interaction analysis, cell culture, and epigenetic studies to identify relevant functional mechanisms that may account for cancer susceptibility. My laboratory has several lines of investigation. 1) Recently, we have analyzed the chromosome 1p11.2 region identified in a breast cancer GWAS.2) We are also performing genetic and functional analysis of associations within the JAZF1 gene and prostate cancer risk. We have re-sequenced the region around a prostate cancer-associated SNP, identified all genetic variants in high linkage disequilibrium, and performed further genotyping and association studies. Through a grant from the Center of Excellence in Integrative Cancer Biology and Genomics (CEICBG, in collaboration with Drs. Natasha Caplen and Stefan Ambs, CCR/NCI), we are combining studies of mRNA expression, siRNA, and pathways analysis to better understand the function of JAZF1. 3) We are investigating the role of the OCLN gene in liver tissue and have found that splicing diversity of this gene may be associated with permissiveness or resistance to HCV infection. Additional work will identify genetic variants within OCLN that may contribute to susceptibility to HCV infection, findings that will have downstream implications for susceptibility to liver cancer. 4) We are pursuing functional analysis on recently identified bladder cancer GWAS signals from a recent study by Rothman et al, 2010. We have explored the regions of the UGT1A and PSCA genes, and are now investigating the CCNE1 gene. |