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.
Coming soon. If you would be interested in discussing projects, please contact us (firstname.lastname@example.org).
Brian Capell, MD, PhD
Amy Anderson, MS
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.
McNeal Andrew S, Liu Kevin, Nakhate Vihang, Natale Christopher A, Duperret Elizabeth K, Capell Brian C, Dentchev Tzvete, Berger Shelley L, Herlyn Meenhard, Seykora John T, Ridky Todd W: CDKN2B Loss Promotes Progression from Benign Melanocytic Nevus to Melanoma. Cancer discovery 5 (10): 1072-85,2015.
Shah Parisha P, Donahue Greg, Otte Gabriel L, Capell Brian C, Nelson David M, Cao Kajia, Aggarwala Varun, Cruickshanks Hazel A, Rai Taranjit Singh, McBryan Tony, Gregory Brian D, Adams Peter D, Berger Shelley L: Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes & development 27 (16): 1787-99,2013.
Capell Brian C, Berger Shelley L: Genome-wide epigenetics. The Journal of investigative dermatology 133 (6): e9,2013.
Conneely Karen N, Capell Brian C, Erdos Michael R, Sebastiani Paola, Solovieff Nadia, Swift Amy J, Baldwin Clinton T, Budagov Temuri, Barzilai Nir, Atzmon Gil, Puca Annibale A, Perls Thomas T, Geesaman Bard J, Boehnke Michael, Collins Francis S: Human longevity and common variations in the LMNA gene: a meta-analysis. Aging cell 11 (3): 475-81,2012.
Capell Brian C, Tlougan Brook E, Orlow Seth J: From the rarest to the most common: insights from progeroid syndromes into skin cancer and aging. The Journal of investigative dermatology 129 (10): 2340-50,2009.
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.