Molecular Genetics & Epigenetics

Cancer is a disease that results from the accumulation of genetic and epigenetic changes, which drive aberrant gene expression and cell cycle progression. The Molecular Genetics and Epigenetics Program (GEN) brings together experts in genome stability, cell cycle, genomics, and epigenetics to form a strong base for a broad understanding of the carcinogenic state. In addition, GEN has an extremely strong computational community to not only harvest the tremendous amounts of genomic data that is available but, more importantly, build new tools to use it to its fullest capacity.

Aim 1: Understand the changes to DNA structure and metabolism that drive cancer

This aim groups scientists studying the changes of DNA structure or DNA damage pathways that drive tumor progression and underlie classic chemotherapeutic treatments. GEN hosts Members with expertise in DNA replication and repair, mitosis and chromosomal instability, DNA damage, and DNA fragile sites.

Aim 2: Understand the changes in gene expression and epigenetics that drive cancer development

Genome-wide genomic and epigenetic methods are revolutionizing biology, and it has become clear that changes in gene expression and epigenetics often drive cancer cell progression. This insight spawned a new wave of targeted therapies that disrupt epigenetic regulators of gene expression. A critical unmet need exists to identify new epigenetic targets and combination therapies that employ inhibitors of epigenetic regulators. This aim coalesces investigators specializing in the changes in epigenetic states and circuitry that drive tumorigenesis. Another group predicts how patient SNPs regulate transcription factor binding underlying cancer predispositions. A third group studies the role of RNAs in the changes of gene regulation in cancer.

Aim 3: Development of computational tools to uncover the changes in gene regulation and mutations that drive cancer

The sequencing revolution enables global views of the changes in cancer cells and whole tumors. However, these rich datasets remain a largely untapped resource. The development of new computational tools will continue to uncover novel cancer drivers, targets, and pathways. GEN assembled outstanding computational biologists from across UVA to build tools to analyze sequence data, and a major role of GEN is to partner these computational biologists with cancer researchers from all of the UVACC Programs.

The program is led by P. Todd Stukenberg, PhD, a leader in the replication and cell cycle fields who has focused more recently on the role of microRNAs in tumorigenesis; and Hui Li, PhD, an expert in trans-splicing as a novel regulatory mechanism in cancer.

Learn more about program members and their research interests.