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Brian C Capell, M.D., Ph.D.
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Assistant Professor of Dermatology
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Medical Staff, Attending Physician, Hospital of the University of Pennsylvania, Department of Dermatology, Philadelphia, PA
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Medical Staff, Active Member, Presbyterian Medical Center, Department of Dermatology, Philadelphia, PA
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Core Faculty, Penn Epigenetics Institute
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Faculty Member, Abramson Cancer Center
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Faculty Member, Penn Institute for Regenerative Medicine
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Medical Staff, Attending Physician, Pennsylvania Hospital, Department of Dermatology, Philadelphia, PA
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Co-Director, Data Sciences and Informatics Core, Penn Skin Biology and Diseases Resource-based Center (SBDRC)
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Department: Dermatology
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Graduate Group Affiliations
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Contact information
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Biomedical Research Building
14 Office: 1007
2f Lab: 1020-21
Philadelphia, PA 19104
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14 Office: 1007
2f Lab: 1020-21
Philadelphia, PA 19104
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Office: 215- 746-8225
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Education:
21 7 BS 14 (Biology) c
27 Boston College, 2000.
21 8 PhD 2b (Cellular and Molecular Biology) c
2c New York University, 2008.
21 7 MD c
3f New York University School of Medicine, 2009.
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Permanent link21 7 BS 14 (Biology) c
27 Boston College, 2000.
21 8 PhD 2b (Cellular and Molecular Biology) c
2c New York University, 2008.
21 7 MD c
3f New York University School of Medicine, 2009.
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71
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10c The Capell Lab seeks to answer fundamental questions regarding how the epigenome impacts cellular homeostasis (i.e. metabolism, immunity), and in turn, how this contributes to cancer, inflammatory disease, and aging of epithelial surface tissues like the skin.
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cd By combining innovative in vivo models and human patient samples with the most cutting-edge epigenetic approaches, we aim to identify therapeutic vulnerabilities and novel targets to treat disease.
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12 BACKGROUND
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1d4 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 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 conditions ranging from aging and cancer to inflammatory disease.
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1d7 For example, there is an exceptionally high incidence of mutations in epigenetic modifiers 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.
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f8 In the Capell Lab, we combine cutting-edge technologies, human patient samples, primary cells, and mouse models in order to investigate major questions at the intersection of epigenetics, epithelial biology, cancer, immunity and metabolism:
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23 EPITHELIAL-IMMUNE INTERPLAY
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32d As the primary barrier to the external environment, epithelial surface tissues like the skin are constantly exposed to a variety of external insults ranging from UV radiation to infection. The epigenome serves as a vital mediator and integrator of these environmental signals, allowing cells to not only respond, but to also form memories of these exposures. In responding to environmental exposures, epithelial cells can also communicate and interface with the local immune and tissue microenvironment. In the Capell Lab, we are interested in not only uncovering these underlying mechanisms, but learning how we can harness the inherent reversibility and targetability of the epigenome in order to prevent and treat common conditions like skin cancer, as well as enhance responses to existing therapies.
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2f DIET, LIPID METABOLISM, AND FERROPTOSIS
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26d Emerging evidence has demonstrated that alterations in lipid metabolism, including those affected by diet, can directly influence oncogenic signaling, programmed cell death pathways, and antitumor immunity. Our lab identified that a major epigenetic tumor suppressor regulates key lipid metabolism genes involved in a form of programmed cell death known as “ferroptosis”, and that ferroptosis may be critical for epithelial differentiation and tumor suppression in SCC. Given the potential to modulate ferroptosis via both small molecules and diet, this provides a great opportunity for therapeutic discovery.
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45 SEX CHROMOSOME COMPLEMENT AND ITS ROLE IN SEX BIAS IN DISEASE
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41a One of the biggest questions in medical research today regards what are the mechanisms that explain sex differences in disease incidence and mortality. Across autoimmune, infectious, and neoplastic disease, sex bias drives significant differences in gene expression as well as disease incidence and outcomes between men and women. While there is evidence for the earlier initiation and worse outcomes in skin cancer among males, approximately 80% of autoimmune disease occurs in females. Despite this, the mechanisms that govern these observed sex disparities have been historically understudied. We hypothesize that a key contributor to sex disparities in epithelial disease is sex chromosome complement, which can lead to gene dosage disparities. In particularly, several epigenetic enzymes exist on either the X or the Y chromosome, and have been implicated in disease pathogenesis in a wide variety of contexts. However, as their roles in skin biology and disease are poorly understood, we are actively investigating these open questions.
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4a If you would be interested in joining our team, please contact us!
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16 LAB PERSONNEL:
1d Brian Capell, MD, PhD
17 Ashley Anderson
11 Lydia Bao
12 Chase Chen
12 Eni Harito
19 Eun Kyung Ko, PhD
19 Nina Kuprasertkul
14 Alyssa Moore
11 Rachel Na
15 Cyria Olingou
13 Gina Pacella
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Description of Clinical Expertise
5d Squamous cell carcinoma and actinic keratoses, basal cell carcinoma, melanoma71
Description of Research Expertise
55 EPIGENETICS AT THE INTERSECTIONS OF CANCER, IMMUNITY, AND METABOLISM8
10c The Capell Lab seeks to answer fundamental questions regarding how the epigenome impacts cellular homeostasis (i.e. metabolism, immunity), and in turn, how this contributes to cancer, inflammatory disease, and aging of epithelial surface tissues like the skin.
8
cd By combining innovative in vivo models and human patient samples with the most cutting-edge epigenetic approaches, we aim to identify therapeutic vulnerabilities and novel targets to treat disease.
8
8
12 BACKGROUND
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1d4 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 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 conditions ranging from aging and cancer to inflammatory disease.
8
1d7 For example, there is an exceptionally high incidence of mutations in epigenetic modifiers 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.
8
f8 In the Capell Lab, we combine cutting-edge technologies, human patient samples, primary cells, and mouse models in order to investigate major questions at the intersection of epigenetics, epithelial biology, cancer, immunity and metabolism:
8
9
23 EPITHELIAL-IMMUNE INTERPLAY
8
32d As the primary barrier to the external environment, epithelial surface tissues like the skin are constantly exposed to a variety of external insults ranging from UV radiation to infection. The epigenome serves as a vital mediator and integrator of these environmental signals, allowing cells to not only respond, but to also form memories of these exposures. In responding to environmental exposures, epithelial cells can also communicate and interface with the local immune and tissue microenvironment. In the Capell Lab, we are interested in not only uncovering these underlying mechanisms, but learning how we can harness the inherent reversibility and targetability of the epigenome in order to prevent and treat common conditions like skin cancer, as well as enhance responses to existing therapies.
8
9
2f DIET, LIPID METABOLISM, AND FERROPTOSIS
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26d Emerging evidence has demonstrated that alterations in lipid metabolism, including those affected by diet, can directly influence oncogenic signaling, programmed cell death pathways, and antitumor immunity. Our lab identified that a major epigenetic tumor suppressor regulates key lipid metabolism genes involved in a form of programmed cell death known as “ferroptosis”, and that ferroptosis may be critical for epithelial differentiation and tumor suppression in SCC. Given the potential to modulate ferroptosis via both small molecules and diet, this provides a great opportunity for therapeutic discovery.
8
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45 SEX CHROMOSOME COMPLEMENT AND ITS ROLE IN SEX BIAS IN DISEASE
8
41a One of the biggest questions in medical research today regards what are the mechanisms that explain sex differences in disease incidence and mortality. Across autoimmune, infectious, and neoplastic disease, sex bias drives significant differences in gene expression as well as disease incidence and outcomes between men and women. While there is evidence for the earlier initiation and worse outcomes in skin cancer among males, approximately 80% of autoimmune disease occurs in females. Despite this, the mechanisms that govern these observed sex disparities have been historically understudied. We hypothesize that a key contributor to sex disparities in epithelial disease is sex chromosome complement, which can lead to gene dosage disparities. In particularly, several epigenetic enzymes exist on either the X or the Y chromosome, and have been implicated in disease pathogenesis in a wide variety of contexts. However, as their roles in skin biology and disease are poorly understood, we are actively investigating these open questions.
8
9
4a If you would be interested in joining our team, please contact us!
8
16 LAB PERSONNEL:
1d Brian Capell, MD, PhD
17 Ashley Anderson
11 Lydia Bao
12 Chase Chen
12 Eni Harito
19 Eun Kyung Ko, PhD
19 Nina Kuprasertkul
14 Alyssa Moore
11 Rachel Na
15 Cyria Olingou
13 Gina Pacella
e 29
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153 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, Sep 2021.
102 Pacella G, Capell BC.: Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma. Exp Dermatol 30(8): 1115-1125, Aug 2021 Notes: doi: 10.1111/exd.14354. Epub 2021 Apr 22.
bf Ko EK, Capell BC.: Methyltransferases in the Pathogenesis of Keratinocyte Cancers. Cancers (Basel) 13: 3402, Jul 2021.
f7 Maldonado López A, Capell BC.: The METTL3-m(6)A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer. Genes (Basel) 12: 1019, Jun 2021.
1a5 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, Feb 2021.
d7 Egolf S, Capell BC: LSD1: a viable therapeutic target in cutaneous squamous cell carcinoma? Expert opin ther targets 24(7): 671-678, Jul 2020.
f8 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, Sep 2019.
1a9 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, Aug 2019.
177 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, Jan 2018.
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Selected Publications
143 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, Dec 2021 Notes: Epub 2021 Dec 10 ; doi: 10.1126/sciadv.abj9141.153 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, Sep 2021.
102 Pacella G, Capell BC.: Epigenetic and metabolic interplay in cutaneous squamous cell carcinoma. Exp Dermatol 30(8): 1115-1125, Aug 2021 Notes: doi: 10.1111/exd.14354. Epub 2021 Apr 22.
bf Ko EK, Capell BC.: Methyltransferases in the Pathogenesis of Keratinocyte Cancers. Cancers (Basel) 13: 3402, Jul 2021.
f7 Maldonado López A, Capell BC.: The METTL3-m(6)A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer. Genes (Basel) 12: 1019, Jun 2021.
1a5 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, Feb 2021.
d7 Egolf S, Capell BC: LSD1: a viable therapeutic target in cutaneous squamous cell carcinoma? Expert opin ther targets 24(7): 671-678, Jul 2020.
f8 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, Sep 2019.
1a9 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, Aug 2019.
177 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, Jan 2018.
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