Associate Professor, Radiation Oncology, Biochemistry and Biophysics
Co-Leader, UNC Lineberger Breast Cancer Research Program
Associate Chair for Research in Radiation Oncology
Associate Director, Medical Scientist Training Program
Associate Director, UNC School of Medicine MD/PhD Program
Breast Cancer, Clinical Research
Area of Interest
Our research interest is to understand the interplay between genome integrity pathways and breast cancer initiation, progression, and response to therapy. The DNA damage response (DDR) is an evolutionarily conserved network of DNA damage sensors, mediators, and effectors that is responsible for maintaining genomic integrity in the face of intrinsic (e.g. oxidized DNA, incorporated ribonucleotides, replication-associated single- and double-strand breaks) and extrinsic (e.g. ionizing radiation, alkylating agents, other clastogen exposures) DNA damage. Germline aberrations in the DDR pathway are known to predispose to cancer (e.g. BRCA1-2, XPA-G, FANCA-P, etc.), but the significance of the DDR in sporadic tumorigenesis is only beginning to emerge.
Recent insights from cancer genome sequencing projects have revealed the remarkable complexity and heterogeneity of genomic aberrations that are observed in human breast cancer. The molecular bases for this genomic complexity remain largely unknown; however, patterns of mutational and structural aberrations have emerged from analyses of cancer genome datasets that suggest underlying defects in DNA repair processes that normally preserve genome integrity during cellular replication. Thus, functional impairment of DDR pathways in sporadic cancers may be a major driver of genetic heterogeneity that fuels progression to metastatic and therapy-resistant disease. Our long-term research goals are to understand the mechanisms that give rise to genomic instability in breast cancer and to identify the molecular vulnerabilities associated with this cancer-specific phenotype. With an improved understanding of these mechanisms and vulnerabilities, we hope to uncover new therapeutic approaches for the most genomically and phenotypically heterogeneous human breast cancers, which are often also the most refractory to treatment.
Our lab utilizes a variety of complementary approaches to tackle this complex topic. Innovative breast cancer mouse models, primary mammary epithelial cell culture, DNA repair/checkpoint assays, RNAi- and CRISPR-based functional genetics, and a variety of genomic assays are all currently being employed.
Awards and Honors
- Burroughs Wellcome Fund Career Award for Medical Scientists, 2013
- Chief Resident, Radiation Oncology, 2012
- Department of Defense Breast Cancer Research Program postdoctoral fellowship award, 2010
- B. Leonard Holman research pathway, approved by the American Board of Radiology, 2009
- Harold M. Weintraub graduate student award, 2007
- Travel award from the Metastasis Research Society, 2006
- Julian R. Rachele prize for best graduate student research paper, 2006
- Vincent du Vigneaud graduate student research prize, 2005
- Katherine Beineke Foundation fellowship, 2004
- Department of Defense Breast Cancer Research Program predoctoral award, 2004
- Medical Scientist Training Program fellowship, 2000
- Francis E. Knock prize in biological chemistry, 2000
- Phi Beta Kappa, 2000
- HHMI undergraduate summer fellowship, 1999
News and Stories
Cancer center researchers to present latest findings at international breast cancer meeting
The San Antonio Breast Cancer Symposium features presentations outlining basic, translational, clinical and community-based study findings focused on advancing the prevention, diagnosis and treatment of breast cancer.
Protein could help identify head and neck cancers that require less intensive treatment
Adding detection of immune cell protein SYNGR3 to current protocols could lead to a more reliable way of determining which patients with head and neck cancer need less intensive treatment.
UNC Lineberger faculty present research at the American Society of Clinical Oncology annual meeting
UNC Lineberger members will be presenting research findings, providing commentary and leading education sessions at the American Society of Clinical Oncology’s 58th annual meeting.
UNC Lineberger researchers to use five year, $3.78 million grant to study tumor mutation and blood tests for HPV-related head and neck cancers
Wendell Yarbrough, MD, MMHC, and colleagues will build upon research that demonstrated tumor and blood tests developed at UNC Lineberger could effectively determine if a patient's cancer had recurred.