Description of Research Expertise

RESEARCH INTERESTS:
The Capell Lab seeks to understand epigenetic and epitranscriptomic gene regulatory mechanisms, how they interface with metabolism and the immune system, and how when disrupted, they may contribute to disease, and in particular, cancer. By combining the incredible accessibility of human skin with the most cutting-edge epigenetic and epitranscriptomic techniques, we aim to identify therapeutic vulnerabilities in cancer, and novel targets to treat disease.

KEYWORDS:
Epigenetics, epitranscriptomics, transcriptional regulation, cancer, aging, cutaneous biology, ferroptosis and lipid metabolism

RESEARCH DETAILS:
Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation. Epigenetic and epitranscriptomic mechanisms provide this precise control through the regulation of gene expression in order to establish and maintain cell fate and identity. Disruption of these pathways can disrupt diverse cellular processes including both metabolism and immunity, and ultimately drive 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 and epitranscriptomic homeostasis may drive epithelial cancers such as SCC is poorly understood.

In the Capell Lab, we combine cutting-edge epigenetic and epitranscriptomic technologies, human patient samples, primary cells, and mouse models in order to solve several fundamental unanswered questions:

- How are epigenetic processes (histone, RNA, DNA) altered by intrinsic (i.e. aging) and extrinsic (i.e. ultraviolet radiation) environmental influences, and how do these changes impact cellular homeostasis (i.e. metabolism, immunity) to promote cancer?

- By elucidating these mechanisms, can we identify new targets and therapeutic vulnerabilities for the prevention and treatment of these potentially deadly cancers?

If you would be interested in joining our team, please contact us!

ROTATION PROJECTS:
If you would be interested in discussing potential rotation projects, please contact us (capellb@pennmedicine.upenn.edu).

LAB PERSONNEL:
Brian Capell, MD, PhD
Shaun Egolf
Sijia Huang, PhD
Eun Kyung Ko, PhD
Nina Kuprasertkul
Alexandra Maldonado-Lopez
Gina Pacella
Jonathan Zou

Selected Publications

Egolf S, Zou J, Anderson A, Simpson CL, Aubert Y, Prouty S, Ge K, Seykora JT, Capell BC: MLL4 mediates differentiation and tumor suppression through ferroptosis Sci Adv 7 (50): eabj9141,2021.

Huang S, Kuri P, Aubert Y, Brewster M, Li N, Farrelly O, Rice G, Bae H, Prouty S, Dentchev T, Luo W, Capell BC, Rompolas P.: Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization Cell Stem Cell ell Stem Cell : 1582-1596,2021.

Pacella G, Capell BC.: Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma Exp Dermatol 30 (8): 1115-1125,2021.

Ko EK, Capell BC.: Methyltransferases in the Pathogenesis of Keratinocyte Cancers Cancers (Basel) 13 : 3402,2021.

Maldonado López A, Capell BC.: The METTL3-m(6)A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer Genes (Basel) 12 : 1019,2021.

Zheng Q, Capell BC, Parekh V, O'Day C, Atillasoy C, Bashir HM, Yeh C, Shim EH, Prouty SM, Dentchev T, Lee V, Wushanley L, Kweon Y, Suzuki-Horiuchi Y, Pear W, Grice EA, Seykora JT.: Whole-Exome and Transcriptome Analysis of UV-Exposed Epidermis and Carcinoma In Situ Reveals Early Drivers of Carcinogenesis J Invest Dermatol 141 : 295-307,2021.

Egolf S, Capell BC: LSD1: a viable therapeutic target in cutaneous squamous cell carcinoma? Expert opin ther targets 24 (7): 671-678,2020.

Aubert Yann, Egolf Shaun, Capell Brian C: The Unexpected Noncatalytic Roles of Histone Modifiers in Development and Disease. Trends in genetics : TIG 35 (9): 645-657,2019.

Egolf Shaun, Aubert Yann, Doepner Miriam, Anderson Amy, Maldonado-Lopez Alexandra, Pacella Gina, Lee Jessica, Ko Eun Kyung, Zou Jonathan, Lan Yemin, Simpson Cory L, Ridky Todd, Capell Brian C: LSD1 Inhibition Promotes Epithelial Differentiation through Derepression of Fate-Determining Transcription Factors. Cell reports 28 (8): 1981-1992.e7,2019.

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.

Academic Contact Information

Biomedical Research Building
Office: 1007
Lab: 1020-21
Philadelphia, PA 19104
Phone: 215-746-8225
Patient appointments: 800-789-7366