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Pharm Sci Seminar – Jennifer Zhang, PhD

April 12 @ 12:00 PM - 12:50 PM

Jennifer Zhang, PhD
Associate Professor in Dermatology
Assistant Professor in Pathology
Duke University

Host: Jun Dai

Inflammatory Signaling Pathways in Skin Development,  Inflammation and Carcinogenesis

As superficial as it is, skin is a complex and dynamic organ and it is the most common site of cancer in the US. Epidermis of the skin undergoes lifelong self-renewal through a tightly regulated balance of cell growth and differentiation. Deregulation of this balance results in barrier defects, inflammation, and cancer. A major effort of the lab is focused on understanding the role of the NF-κB and MAPK signaling pathways in epidermal cell growth and differentiation.

Using de novo regenerated transgenic human skin tissues, we have previously demonstrated that Ras oncogene coupled with NF-κB loss or JNK/AP1 activation is sufficient to transform normal human keratinocytes into cancer cells. In our current studies, we used murine genetic animal models to demonstrate that keratinocyte-targeted BRAF activation induces epidermal and sweat gland neoplasia. We found that topical MEK inhibition mitigated BRAF-driven skin lesions, as well as UV-induced skin carcinogenesis and chemically-induced dermatitis. In agreement with NF-κB being a key epidermal growth regulator and promoter of aging, epidermis-targeted inactivation of CYLD, a deubiquitinase inhibitory of NF-κB, leads to the development of hair follicle defects and inflammation, and sensitizes animals to the development of basaloid and sebaceous skin tumors. This was accompanied by increased activation of NF-κB, AP1, and Myc gene regulators, as well as androgen receptor (AR) signaling. We suggest that these inflammatory signaling pathways and dominant gene regulators represent topically applicable therapeutic targets for various skin diseases.

Another aspect of our study is focused on understanding the role of the inflammatory signaling pathways in melanoma. We have demonstrated that CYLD inhibits melanoma growth through suppression of the JNK/AP1 and β1-integrin signaling pathways. In contrast, UBE2N, a K63-ubiquitin conjugase, promotes melanoma growth through activation of the MEK/FRA1/SOX10 signaling cascade. Our findings suggest that UBE2N and other ubiquitin enzymes may targeted for melanoma therapy.

Details

Date:
April 12
Time:
12:00 PM - 12:50 PM
Event Category:
Website:
https://pharmacy.wisc.edu/student-organizations/sccp/

Venue

1116 Rennebohm Hall
777 Highland Ave
Madison, WI 53705 United States
Website:
https://pharmacy.wisc.edu/about/rennebohm-hall/

Organizer

Pharmaceutical Sciences Division
Phone:
608-262-0353
Website:
https://pharmacy.wisc.edu/psd

Other

Speaker
Jennifer Zhang, PhD
Presentation Title
Inflammatory Signaling Pathways in Skin Development, Inflammation and Carcinogenesis