Cancer involves inherited and acquired gene mutations that confer ectopic expression of proteins and/or create aberrant protein products. These alterations disrupt genetic and signaling networks responsible for maintaining homeostasis.
The Genetic and Epigenetic Mechanisms (GEM) pursues basic and translational research to discover novel cancer genetic and epigenetic mechanisms, to translate mechanistic insights derived principally from mouse models and primary human cancer samples to human cancer, and to leverage the mechanistic insights to advance cancer diagnosis and treatment. GN investigators develop new technologies to better detect variants, deploy mechanistic studies to discover the functional consequences of variants and engage in translational efforts to exploit these variants for better prevention, early detection and therapy.
Program members bring diverse and complementary skills to these collaborative efforts. Some specialize in omics-technology development, others specialize in computational approaches to decipher big data generated in cancer research, while others are experts in biological and mechanistic dissection of problems involving cancer genetics and epigenetics. GN investigators aim to advance the program's broad goals to better detect, characterize, and exploit cancer-relevant genetic and epigenetic mechanisms. Importantly, a common thread of the GN efforts is the seamless interactions between physician scientists, with active clinical roles, and scientists dedicated to dissecting cancer mechanisms.
Thematic areas of emphasis include:
- Fundamental and Translational Epigenetics: Epigenetics is a thriving thematic area within the program, with the strong mechanistic and biological work of GN members who constitute the Wisconsin Institute of Discovery (WID) Epigenetics Theme (Drs. Denu and Lewis), and with intra-programmatic teams studying epigenetic mechanisms underlying breast cancer (Drs. Xu and Coon), prostate cancer (Drs. Jarrard and Denu) and AML (Drs. Bresnick, Keles, and Dewey). Major goals include elucidating novel genetic and epigenetic mechanisms, deciphering how aberrations in the mechanisms corrupt genetic networks as a cancer mechanism, and how the disease mechanisms can be exploited for biomarker and drug development.
- Hormone-Regulated Cancers: Intersecting with the fundamental and translational epigenetics work are research efforts involving murine and human genetics and predictive modeling tools focused on understanding mechanistic underpinnings of breast and ovarian cancers. A major goal is to identify novel genetic and epigenetic mechanisms affecting breast cancer susceptibility and to inform drug development. A second goal is to develop diagnostic, prognostic, and predictive biomarkers for breast, ovarian and prostate cancer. These efforts are exemplified by the uniquely strong teams of Drs. Page and Burnside, Drs. Gould and Gumperz, and Drs. Jarrard and Denu.
- Decoding Genome and Proteome Function: Diverse genomic aberrations are involved in the initiation and progression of cancer, and better technologies are needed to rapidly identify genomic aberrations. A major goal is to devise and implement novel technologies to gain functional insights into human genomes and proteomes. A second goal is to foster collaborations between technology innovators and GN members with biologically- and mechanistically- and disease-focused programs. These efforts are exemplified by the exceptional expertise of Drs. Josh Coon and Lloyd Smith who synergize with, and therefore catalyze, efforts of multiple GN members, as well as Drs. Keles and Dewey, exceptional computational biologists with a focus on genome science.