Cancer Genetics and Genomics (CGG)
Cancer is a disease of disordered genetic and epigenetic regulation. It starts and progresses via the acquisition of changes in the genome that result in the development of the malignant phenotype. The Cancer Genetics and Genomics Research Program (CGG) serves to coordinate the Duke Cancer Institute (DCI) research activities related to the study and understanding of cancer genomics, epigenetics, gene expression, model systems and host interactions. The CGG is at the forefront of applying 'omics' technologies that assess alterations in cancer genomes, epigenomes and transcriptomes, or techniques that are capable of editing the genome or epigenome of a model system. The program serves as the primary source of expertise in the DCI for these aspects of cancer.
The CGG program features enhanced interactions among program investigators and with investigators of other DCI programs. Importantly CGG encourages strong interactions between its members and those of clinical programs as a route to translate the basic science findings obtained by the CGG program.
The CGG program supports genomic resources for the DCI: Genomics encompasses a set of enabling high throughput methods that enable the work of researchers throughout the DCI. A particular strength of the CGG program is the genomics expertise that resides in the program. Several members, including Drs. Dave, Hsu, Owzar, Katsanis, and Gregory are highly experienced in cancer genomics and have broad collaborations within the program and with other programs that enable the DCI community to use these cutting edge tools. Thus, genomics expertise is disseminated to all DCI members through the focus groups and program-wide activities.
Aim #1: Foster interactions and collaborations around cancer genetics and genomics in the DCI.
To this aim we have developed program-wide and focus group activities. The program-wide activities include a monthly lunch talk series, the CGG yearly mini-symposium, and the CGG annual grand rounds speaker. These are all well-attended and bring together a diverse group of investigators around the central themes of cancer genetics and genomics.
CGG is further organized into three focus groups: (a) The Focus Group on Genomics, Epigenetics and Model systems. (b) The Focus Group on DNA Recombineering and Repair. (c) The Focus Viral Oncology and Microbiomes. The different focus groups organize distinct monthly research-in-progress sessions; all CGG members are welcomed to attend and indeed all DCI members can attend any of these meetings. The focus group activities provide additional opportunities for training, mentorship and interaction around more focused themes.
Aim #2: Promote sharing of expertise in computational and functional genomics in the DCI.
The advent of high throughput sequencing and genome editing provides powerful technologies that allow the high resolution definition of molecular aberrations of tumors and the tools to explore these mutations in an in vitro and in vivo setting. Through targeted investment in high throughput genomics, the DCI has enabled collaborations around high throughput sequencing, and transgenic mouse and RNAi facilities.
This investment has allowed the critical program growth in genomics that exploits rapid advances in sequencing technologies for genomic germline and somatic profiling, the quantitative and discovery analysis of transcriptomes, and the ability to generate detailed epigenetic profiles that alter during tumorigenesis, such as DNA methylation. These data provide a rich source of information for aggregation to interpret cancer related mechanisms. This investment has in turn enabled a number of inter-program and inter-institutional collaborations within the DCI and beyond.
The program serves to coordinate DCI research activities related to:
1. Cancer genetics and model systems
2. Understanding the altered epigenetics and gene expression (transcriptional and post - transcriptional) that occurs in cancers
3. Application of genomics technologies to assay alterations in cancer genomes, epigenomes and transcriptomes.
Sandeep Dave, MD, MS is a physician-scientist and clinical oncologist. He is an associate professor of Medicine at the Center for Genomic and Computational Biology at Duke University. He completed medical school and graduate school at Northwestern University, and a clinical and post-doctoral fellowship at the National Institutes of Health. He is the PI of several peer-reviewed grants including two R01 grants and an R21 grant from the NCI as well those from other agencies including the Leukemia Lymphoma Society and the Department of Defense. His work has applied high throughput sequencing to unravel the genetic causes of lymphoma (e.g. Love et al, Nature Genetics 2012) and for understanding the molecular underpinnings of response to targeted therapies (e.g. Walsh et al, Clin Canc Research 2013). Dave also leads the international Hematologic Malignancies Research Consortium, an international group of collaborating institutions that is focused on applying genomics to better define these cancers. The consortium includes several NCI-designated Comprehensive Cancer Centers.
Sue Jinks-Robertson, PhD is a professor in the Department of Molecular Genetics and Microbiology. She obtained a PhD in Genetics from the University of Wisconsin, Madison and completed postdoctoral work at the University of Chicago before joining the faculty of Emory University in 1987. Jinks-Robertson moved to Duke in 2006 and currently is vice chair of her department and director of the T32-funded Cell and Molecular Biology graduate training program. Her research focuses on the regulation of genome stability in the budding yeast model system and is funded by R35 and R21 grants from the NIH.
Dave and Jinks-Robertson organize the monthly program-wide meetings and host the external speakers for the monthly meeting and the yearly symposium. In close collaboration with Michael Kastan, PhD, executive director of Duke Cancer Institute, the program leaders have re-invigorated this program by merging two pre-existing programs, re-evaluating the membership, identifying the leadership for focus groups, and recruiting new faculty to Duke and the DCI.
1. Genomics, Epigenetics and Model systems (Leader, Dr. Beth Sullivan)
2. DNA Replication and Recombineering (Leader, Dr. Sue Jinks-Robertson)
3. Viral Oncology and Microbiomes (Leaders, Drs. Arno Greenleaf and Micah Luftig)
Bogerd, HP, Kornepati, AV, Marshall, JB, Kennedy, EM, and Cullen, BR. "Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators." Proceedings of the National Academy of Sciences of the United States of America 112, no. 52 (December 14, 2015): E7249-E7256. PMID: 26668372
Thakore, PI, D'Ippolito, AM, Song, L, Safi, A, Shivakumar, NK, Kabadi, AM, Reddy, TE, Crawford, GE, and Gersbach, CA. "Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements." Nature Methods 12, no. 12 (December 2015): 1143-1149. PMID: 26501517
Aligeti, M, Roder, A, and Horner, SM. "Cooperation between the Hepatitis C Virus p7 and NS5B Proteins Enhances Virion Infectivity." Journal of Virology 89, no. 22 (November 2015): 11523-11533. PMID: 26355084
Price, AM, and Luftig, MA. "To be or not IIb: a multi-step process for Epstein-Barr virus latency establishment and consequences for B cell tumorigenesis." PLoS Pathogens 11, no. 3 (March 19, 2015): e1004656-. PMID: 25790223
DCI Research Programs
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