This application supports the career development of Brian Poligone, MD, PhD. who has an interest in the molecular signaling of NF-KB and its effect on the skin. The transcription factor NF-KB provides a regulatory on/off switch for gene expression that is important for inflammation and carcinogenesis. By understanding the role of NF-KB in the biology of keratinocytes and cutaneous lymphoid cells, inflammatory skin diseases and cancers may be better understood. We have constructed a novel mouse model to examine the NF-KB pathway in skin. The homozygous p65 S276D (PD) knock-in mouse contains a mutant form of NF-KB that increases the basal transcriptional activation of NF-KB dependent genes. Because studies on NF-KB activity in the skin have been underrepresented, detailed examination of the PD mouse should help clarify this central mediator of inflammation and tumorigenesis. Transcription factors are proteins that are the main on/off switch in regulating gene expression. NF-KB is a transcription factor that is known to be a central regulator of both inflammatory and oncogenic processes. Studying NF-KB in genetically engineered mouse models helps to clarify the role of NF-KB and allows a better understanding of its activity in inflammatory disease and cancer and ultimately may lead to improved patient care.

Public Health Relevance

By understanding the basic mechanisms that lead to both skin inflammation and tumorigenesis, better treatments for skin disease are possible. It is through this basic understanding of skin disease that better treatments of can be identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR055986-05
Application #
8514524
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Cibotti, Ricardo
Project Start
2009-09-25
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$120,922
Indirect Cost
$8,957
Name
University of Rochester
Department
Dermatology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Poligone, Brian; Gilmore, Elaine S; Alexander, Carolina V et al. (2015) PKK suppresses tumor growth and is decreased in squamous cell carcinoma of the skin. J Invest Dermatol 135:869-76
Wahrendorf, Morten; Reinhardt, Jan D; Siegrist, Johannes (2013) Relationships of disability with age among adults aged 50 to 85: evidence from the United States, England and continental europe. PLoS One 8:e71893
Poligone, Brian; Heald, Peter (2012) Menus for managing patients with cutaneous T-cell lymphoma. Semin Cutan Med Surg 31:25-32
Poligone, Brian; Heald, Peter (2010) Innovative therapy of cutaneous T-cell lymphoma: beyond psoralen and ultraviolet light and nitrogen mustard. Dermatol Clin 28:501-10