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 epigenefic aberrafions are hallmarks of cancer and drive malignant behavior. The goals of the Molecular Genetics and Epigenetics Program are to understand the underiying molecular basis of these aberrafions and to speed the ufilization of that understanding to improve cancer diagnosis, prognosis, prevenfion, and therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
2P30CA044579-21
Application #
8231124
Study Section
Subcommittee G - Education (NCI)
Project Start
2012-02-01
Project End
2017-01-31
Budget Start
2012-06-05
Budget End
2013-01-31
Support Year
21
Fiscal Year
2012
Total Cost
$28,732
Indirect Cost
$10,509
Name
University of Virginia
Department
Type
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Knapp, Kiley A; Pires, Eusebio S; Adair, Sara J et al. (2018) Evaluation of SAS1B as a target for antibody-drug conjugate therapy in the treatment of pancreatic cancer. Oncotarget 9:8972-8984
Zhang, Xuewei; Kitatani, Kazuyuki; Toyoshima, Masafumi et al. (2018) Ceramide Nanoliposomes as a MLKL-Dependent, Necroptosis-Inducing, Chemotherapeutic Reagent in Ovarian Cancer. Mol Cancer Ther 17:50-59
Kedzierska, Katarzyna Z; Gerber, Livia; Cagnazzi, Daniele et al. (2018) SONiCS: PCR stutter noise correction in genome-scale microsatellites. Bioinformatics 34:4115-4117
Balogh, Kristen N; Templeton, Dennis J; Cross, Janet V (2018) Macrophage Migration Inhibitory Factor protects cancer cells from immunogenic cell death and impairs anti-tumor immune responses. PLoS One 13:e0197702
Cruickshanks, Nichola; Zhang, Ying; Hine, Sarah et al. (2018) Discovery and Therapeutic Exploitation of Mechanisms of Resistance to MET Inhibitors in Glioblastoma. Clin Cancer Res :
Rodriguez, Anthony B; Peske, J David; Engelhard, Victor H (2018) Identification and Characterization of Tertiary Lymphoid Structures in Murine Melanoma. Methods Mol Biol 1845:241-257
Gonzalez, Phillippe P; Kim, Jungeun; Galvao, Rui Pedro et al. (2018) p53 and NF 1 loss plays distinct but complementary roles in glioma initiation and progression. Glia 66:999-1015
Melhuish, Tiffany A; Kowalczyk, Izabela; Manukyan, Arkadi et al. (2018) Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Biochim Biophys Acta Gene Regul Mech 1861:983-995
Stowman, Anne M; Hickman, Alexandra W; Mauldin, Ileana S et al. (2018) Lymphoid aggregates in desmoplastic melanoma have features of tertiary lymphoid structures. Melanoma Res 28:237-245
Carlton, Anne L; Illendula, Anuradha; Gao, Yan et al. (2018) Small molecule inhibition of the CBF?/RUNX interaction decreases ovarian cancer growth and migration through alterations in genes related to epithelial-to-mesenchymal transition. Gynecol Oncol 149:350-360

Showing the most recent 10 out of 539 publications