Jennifer Yunyan Zhang
Professor in Dermatology
Overview
Epidermis of the skin constitutes the largest organ and the outer most barrier of the body. It is one of the few organs that undergo lifelong self-renewal through a tight balance of cell growth, differentiation, and programmed cell death. Deregulation of this balance is manifested in many diseases, including various immune diseases and cancer.
Our lab is focused on 3 interrelated topics:
1. Gene regulation of epithelial cell proliferation and differentiation
Using regenerated human skin tissues and murine genetic models, we have demonstrated important functions NF-kB and AP-1 gene regulators in epidermal cell growth and differentiation. Currently, our efforts are focused on understating how loss-of-function of CYLD, a deubiquitinase and tumor suppressor, leads to the development of hair follicle defects, skin inflammation, and cancer. Specifically, we want to determine how CYLD integrates NF-kB, AP1, Myc, and other transcription factors to control epidermal cell growth and lineage differentiation.
De novo skin regeneration is life-saving procedure for severely burned patients and lethal genetic skin diseases such as epidermal bullosa. An additional aspect of our study is to improve new skin regeneration techniques and to create experimental skin disease models with gene transduced keratinocytes, as illustrated below.
2. Keratinocytes as instigators of inflammatory responses
Keratinocytes are constantly challenged by external insults, as well as immune cells. Disarray of the crosstalk between keratinocytes and immune cells underlies various immune diseases, including dermatitis, psoriasis, and cutaneous graft-versus-host disease (GVHD). GVHD is a common complication and the leading cause of non-relapse mortality among patients after receiving allogenic hematopoietic stem cell transplantation. The skin is the most commonly affected organ in both the acute and chronic forms of this disease. Treatment options for GVHD are limited and the current standard therapy is high dose systemic corticosteroid which is itself associated with significant morbidity. Our goal is to understand how keratinocytes contribute to the progression of GVHD, and may therefore be targeted to mitigate the disease.
3. Ubiquitination enzymes in melanoma
Melanoma most lethal and difficult to treat skin cancer. In the recent years, BRAF/MEK-targeted therapies have produced exciting results, but they suffer from short duration. Our goal is to uncover novel mechanisms crucial for melanoma malignancy. Specifically, we want to understand how ubiquitination enzymes contribute to melanoma growth. Previously, we have demonstrated that CYLD inhibits melanoma growth through suppression of JNK/AP1 and b1-integrin signaling pathways. In contrast, UBE2N, a K63-Ubiquitin conjusage, promotes melanoma growth in part through activation of the MEK/FRA/SOX10 signaling cascade. Currently, our efforts are focused on understanding how UBE2N and other ubiquitin enzymes regulate the MAPK signaling pathway and whether they can be targeted for melanoma therapy.
Positions
Professor in Dermatology in the School of Medicine
2022 School of Medicine
Professor in Pathology in the School of Medicine
2022 School of Medicine
Member of the Duke Cancer Institute in the School of Medicine
2005 School of Medicine
Affiliate of the Duke Regeneration Center in the School of Medicine
2021 School of Medicine
Education
Ph.D. 1998
1998 University of Florida
Postdoctoral Fellow, Molecular And Cellular Biology, Immunology
2000 University of California San Francisco, School of Medicine
Postdoctoral Associate, Molecular And Cellular Biology, Cancer Biology
2005 Stanford University, School of Medicine
Publications, Grants & Awards
- Grants (20)
- Academics Articles (62)
- Conference Pages (12)
- Book Sections (3)
National Institutes of Health
National Institutes of Health
National Institutes of Health
Department of Defense
National Institutes of Health
National Institutes of Health
National Institutes of Health
University of North Carolina - Chapel Hill
MicroElastic Ultrasound Systems, Inc.
National Institutes of Health
Society for Investigative Dermatology
Massachusetts General Hospital
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
International Journal of Biological Macromolecules
Nature Communications
Bio Protocol
Stem Cell Reports
Frontiers in Oncology
Mrs Communications
Gastroenterology
Scientific Reports
Frontiers in Medicine
Frontiers in Immunology
J Tissue Eng Regen Med
Journal of Investigative Dermatology
J Invest Dermatol
J Invest Dermatol
Int J Bioprint
Jci Insight
The Journal of Biological Chemistry
Journal of Biomedical Optics
J Invest Dermatol
J Invest Dermatol
Clin Exp Dermatol
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Progress in Biomedical Optics and Imaging Proceedings of Spie
Cancer Research
Biomedical Optics, BIOMED 2012
American Journal of Cancer Research
Optics Infobase Conference Papers
Optics Infobase Conference Papers
Optics Infobase Conference Papers
Cancer Prev Res (Phila)
Biomedical Optics Express
J Invest Dermatol
Cell Adh Migr
Cell Research
Genes & Development
Cancer Research
The Journal of Cell Biology
Genes & Development
Genes & Development
The Journal of Immunology
Journal of Investigative Dermatology
Progress in Biomedical Optics and Imaging Proceedings of Spie
Journal of Investigative Dermatology
Optics Infobase Conference Papers
Optics Infobase Conference Papers
Journal of Investigative Dermatology
Cancer Research
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Genetic Mutations and Ubiquitination in Melanoma Growth and Metastasis
Animal Models for the Study of Human Disease: Second Edition
Animal Models for the Study of Human Disease
Offices & Contact
Durham, NC
27710 Rm 4130, MSRB III Bldg, 3 Genome Ct
Durham, NC
27705