MOLECULAR GENETICS AND EPIGENETICS PROGRAM (GEN) ? ABSTRACT The accumulation of heritable genetic and epigenetic changes that result in loss of function 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 underlie these defects and to uncover new targets for therapy, diagnosis, prognosis, and prevention. The Program capitalizes on the large number of outstanding investigators at UVA with research expertise in chromatin architecture, transcription, replication, mutation, repair, genomics and cellular checkpoints in cancer. The Members are organized around three main themes: (1) Chromosome function, malfunction, and cellular checkpoints; (2) Gene expression and epigenetics and cancer; (3) noncoding RNAs in cancer. The Program is led by James L. Larner, MD, PhD, chair of Radiation Oncology and an expert in DNA damage responses to radiation; and by P. Todd Stukenberg, PhD a leader in the mitosis and cell cycle fields. Through its activities, GEN provides a formal mechanism for fostering intellectual exchange and collaboration among its Members. The Program currently consists of 25 Full Members and 6 Associate Members from 11 different departments. Ten 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 radiation and cellular responses to radiation. GEN has added a significant cohort of translational and clinical investigators whose research focus is on particular tumor types, including lung and brain tumors, or on radiation damage. Total extramural funding for the Program exceeds $8.3M, including $4.1 million from the National Cancer Institute (NCI) and over $3.1M from other NIH institutes. GEN is composed of highly productive and collaborative members with 373 total publications in the last grant period and of these 22% are intra-programmatic and 29% are inter-programmatic with other UVA Cancer Center Programs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA044579-30
Application #
10091448
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
1997-09-16
Project End
2022-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
30
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Olmez, Inan; Zhang, Ying; Manigat, Laryssa et al. (2018) Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma. Cancer Res 78:4360-4369
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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

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