The accumulation of heritable genetic and epigenefic changes that result in loss of funcfion of tumor suppressors and/or inappropriate activation of proto-oncogenes is a hallmark of cancer. The goals of the Molecular Genetics and Epigenetics Program (GEN) are to understand the molecular mechanisms that underiie these defects and to uncover new targets for therapy, diagnosis, prognosis, and prevention. The Program capitalizes on the large number of outstanding invesfigators at UVA with research expertise in chromafin architecture, transcription, replicafion. mutation, repair, and cellular checkpoints in cancer. The Members are organized around four main themes: (1) Chromosome funcfion, malfunction, and cellular checkpoints;(2) Epigenefics and cancer;(3) Signaling and gene expression in cancer;and (4) Bioinformatics: mining informafion from human genomes. The Program is led by Joyce L. Hamlin, PhD, an expert in mammalian DNA replicafion and large-scale chromosome rearrangements in tumor cells;and by Anindya Dutta, MD, PhD a leader in the replicafion and cell cycle fields. Dr. Dutta has focused more recenfiy on the role of microRNAs in tumorigenesis. Through its acfivities. GEN provides a formal mechanism for fostering intellectual exchange and collaboration among its Members. The Program currently consists of 32 Full Members and 6 Associate Members from 11 different departments. Twenty one of these individuals are new to the Program or to UVA since the last renewal, and they bring considerable expertise in the bioinformatics of microarray and deep-sequencing data, large-scale genomic rearrangements (including aneuploidy). and the molecular effects of radiafion and cellular responses to radiation. Importanfiy for this renewal, GEN has added a significant cohort of translafional and clinical invesfigators whose research focus is on particular tumor types, including lung and brain tumors, or on radiafion damage. Total extramural funding for the Program exceeds $14.8 million, including $3.4 million from the Nafional Cancer Institute (NCI) and an award from the American Cancer Society. Program Members have produced 390 cancer-relevant publicafions, of which 32% were inter-programmatic and 18% were intra-programmatic since the last renewal. In addition. Program Members participate in multi-invesfigator and collaborative Nafional Insfitutes of Health research awards, including 18 grants from NCI.

Public Health Relevance

Genetic and epigenetic aberrations are hallmarks of cancer and drive malignant behavior. The goals of the Molecular Genetics and Epigenetics Program are to understand the underlying molecular basis of these aberrations and to speed the utilization of that understanding to improve cancer diagnosis, prognosis, prevention, and therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA044579-23
Application #
8635288
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
23
Fiscal Year
2014
Total Cost
$10,657
Indirect Cost
$5,180
Name
University of Virginia
Department
Type
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Banizs, Anna B; Huang, Tao; Nakamoto, Robert K et al. (2018) Endocytosis Pathways of Endothelial Cell Derived Exosomes. Mol Pharm :
Jia, Deshui; Augert, Arnaud; Kim, Dong-Wook et al. (2018) Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition. Cancer Discov 8:1422-1437
Manukyan, Arkadi; Kowalczyk, Izabela; Melhuish, Tiffany A et al. (2018) Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors. J Cell Biochem 119:4644-4655
Engelhard, Victor H; Rodriguez, Anthony B; Mauldin, Ileana S et al. (2018) Immune Cell Infiltration and Tertiary Lymphoid Structures as Determinants of Antitumor Immunity. J Immunol 200:432-442
Martins, André L; Walavalkar, Ninad M; Anderson, Warren D et al. (2018) Universal correction of enzymatic sequence bias reveals molecular signatures of protein/DNA interactions. Nucleic Acids Res 46:e9
Michaels, Alex D; Newhook, Timothy E; Adair, Sara J et al. (2018) CD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer. Clin Cancer Res 24:1415-1425
Shi, Lei; Li, Kang; Guo, Yizhan et al. (2018) Modulation of NKG2D, NKp46, and Ly49C/I facilitates natural killer cell-mediated control of lung cancer. Proc Natl Acad Sci U S A 115:11808-11813
Yang, Jun; LeBlanc, Francis R; Dighe, Shubha A et al. (2018) TRAIL mediates and sustains constitutive NF-?B activation in LGL leukemia. Blood 131:2803-2815
Kulling, Paige M; Olson, Kristine C; Hamele, Cait E et al. (2018) Dysregulation of the IFN-?-STAT1 signaling pathway in a cell line model of large granular lymphocyte leukemia. PLoS One 13:e0193429
Grant, Margaret J; Loftus, Matthew S; Stoja, Aiola P et al. (2018) Superresolution microscopy reveals structural mechanisms driving the nanoarchitecture of a viral chromatin tether. Proc Natl Acad Sci U S A 115:4992-4997

Showing the most recent 10 out of 539 publications