Overview
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.
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.
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.
Current Appointments & Affiliations
Recent Publications
Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics.
Journal Article JID Innov · July 2025 Cutaneous manifestations are the most common presenting sign of chronic graft-versus-host disease (GVHD), and the extent of cutaneous involvement is also highly correlated with prognosis. Very little is understood about the underlying pathogenesis underpin ... Full text Link to item CiteCutaneous dysbiosis characterizes the post-allogeneic hematopoietic stem cell transplantation period.
Journal Article Blood Adv · May 13, 2025 Gut dysbiosis is linked to mortality and the development of graft-versus-host disease after hematopoietic stem cell transplantation (HSCT), but the impact of cutaneous dysbiosis remains unexplored. We performed a pilot observational study, obtained retroau ... Full text Link to item CiteNeuronal Mechanisms of Psoriatic Itch: Role of IL-17R/ERK/TRPV4 Signaling Pathway.
Journal Article J Invest Dermatol · April 17, 2025 Itch represents a major disease burden of psoriasis. Despite recent clinical studies showing the effectiveness of IL-17- and IL-17R-blocking antibodies in alleviating psoriatic itch, significant questions remain unanswered. Specifically, the crucial cellul ... Full text Link to item CiteRecent Grants
The Duke Preparing Research scholars In bioMEdical sciences (PRIME): Cancer Research Program
ResearchPreceptor · Awarded by National Cancer Institute · 2023 - 2028Bidirectional control of keratinocyte differentiation and proliferation by transcription factor FOXQ1
ResearchCo Investigator · Awarded by National Institutes of Health · 2023 - 2028Targeting myeloid cells of the tumor microenvironment
ResearchPrincipal Investigator · Awarded by Melanoma Research Alliance · 2025 - 2028View All Grants