Description of Research Expertise:
The Capell Lab seeks to understand how epigenetic and chromatin regulatory mechanisms contribute to disease. By combining the incredible accessibility of human skin with the most cutting-edge epigenetic and genome-wide techniques, we aim to identify novel targets to treat disease.
Epigenetics, transcriptional regulation, enhancers, skin cancer, aging
Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation. Epigenetic mechanisms provide this precise control through the regulation of gene enhancer and transcriptional networks that establish and maintain cell fate and identity. Disruption of these pathways can lead to a loss of proliferative control, ultimately driving cancer.
Consistent with this, chromatin regulators are amongst the most frequently mutated genes in all of cancer, with an exceptionally high incidence of mutations in cancers of self-renewing epithelial tissues, such as squamous cell carcinoma (SCC). SCC is the most common type of cancer worldwide, affecting numerous epithelial tissues ranging from the skin and eyes to the lung, esophagus, and oropharynx. Despite this, precisely how disruption of epigenetic homeostasis may drive epithelial cancers such as SCC is poorly understood.
In the Capell Lab, we combine cutting-edge epigenetic technologies, human patient samples, primary cells, and mouse models in order to solve several fundamental unanswered questions:
1) How is the skin epigenome altered by intrinsic (i.e. aging) and extrinsic (i.e. ultraviolet radiation) environmental influences, and how do these changes contribute to disease?
2) How do chromatin regulatory enzymes function in both normal and diseased skin, particularly during carcinogenesis?
3) Can we target the epigenome with precision to treat disease?
Through this, we hope to identify new epigenetic targets for prevention and treatment of these potentially deadly cancers.
If you would be interested in discussing potential rotation projects, please contact us (firstname.lastname@example.org).
Brian Capell, MD, PhD
Amy Anderson, MS
Yann Aubert, PhD
Lin-Shiao Enrique, Lan Yemin, Coradin Mariel, Anderson Amy, Donahue Greg, Simpson Cory L, Sen Payel, Saffie Rizwan, Busino Luca, Garcia Benjamin A, Berger Shelley L, Capell Brian C: KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis. Genes & development 32 (2): 181-193,2018.
Ghosh Kanad, O'Neil Kyle, Capell Brian C: Histone modifiers: Dynamic regulators of the cutaneous transcriptome. Journal of dermatological science 89 (3): 226-232,2018.
Dou Zhixun, Ghosh Kanad, Vizioli Maria Grazia, Zhu Jiajun, Sen Payel, Wangensteen Kirk J, Simithy Johayra, Lan Yemin, Lin Yanping, Zhou Zhuo, Capell Brian C, Xu Caiyue, Xu Mingang, Kieckhaefer Julia E, Jiang Tianying, Shoshkes-Carmel Michal, Tanim K M Ahasan Al, Barber Glen N, Seykora John T, Millar Sarah E, Kaestner Klaus H, Garcia Benjamin A, Adams Peter D, Berger Shelley L: Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550 (7676): 402-406,2017.
Ghosh Kanad, Capell Brian C: The Senescence-Associated Secretory Phenotype: Critical Effector in Skin Cancer and Aging. The Journal of investigative dermatology 136 (11): 2133-2139,2016.
Capell Brian C, Drake Adam M, Zhu Jiajun, Shah Parisha P, Dou Zhixun, Dorsey Jean, Simola Daniel F, Donahue Greg, Sammons Morgan, Rai Taranjit Singh, Natale Christopher, Ridky Todd W, Adams Peter D, Berger Shelley L: MLL1 is essential for the senescence-associated secretory phenotype. Genes & development 30 (3): 321-36,2016.
Dou Zhixun, Xu Caiyue, Donahue Greg, Shimi Takeshi, Pan Ji-An, Zhu Jiajun, Ivanov Andrejs, Capell Brian C, Drake Adam M, Shah Parisha P, Catanzaro Joseph M, Ricketts M Daniel, Lamark Trond, Adam Stephen A, Marmorstein Ronen, Zong Wei-Xing, Johansen Terje, Goldman Robert D, Adams Peter D, Berger Shelley L: Autophagy mediates degradation of nuclear lamina. Nature 527 (7576): 105-9,2015.
Capell Brian C, Berger Shelley L: Genome-wide epigenetics. The Journal of investigative dermatology 133 (6): e9,2013.
Capell Brian C, Olive Michelle, Erdos Michael R, Cao Kan, Faddah Dina A, Tavarez Urraca L, Conneely Karen N, Qu Xuan, San Hong, Ganesh Santhi K, Chen Xiaoyan, Avallone Hedwig, Kolodgie Frank D, Virmani Renu, Nabel Elizabeth G, Collins Francis S: A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proceedings of the National Academy of Sciences of the United States of America 105 (41): 15902-7,2008.
Capell Brian C, Collins Francis S: Human laminopathies: nuclei gone genetically awry. Nature reviews. Genetics 7 (12): 940-52,2006.
Capell Brian C, Erdos Michael R, Madigan James P, Fiordalisi James J, Varga Renee, Conneely Karen N, Gordon Leslie B, Der Channing J, Cox Adrienne D, Collins Francis S: Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proceedings of the National Academy of Sciences of the United States of America 102 (36): 12879-84,2005.