Paul A. Khavari, MD, PhD
Academic Appointments
- Professor, Dermatology
- Member, Bio-X
- Member, Cancer Center
Contact Information
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Academic Offices
Administrative Contact Pam Bernstein Program Director Email Tel Work 650/498-6295
Education & Community
Postdoctoral Advisees
Xiaomin Bao, Ross Flockhart, Markus Kretz, Vanessa Lopez-Pajares, Todd Ridky, George Sen, Brian Zarnegar
Graduate & Fellowship Program Affiliations
Web Site Links
Scientific Focus
Research Interests
Our experimental focus is on the mammalian setting, including mouse genetics, human genetics and new human tissue platforms. The latter encompass human skin regenerated on immune deficient mice as well as organotypic constructs with epithelial and stromal cells embedded within architecturally faithful mesenchyma in vitro. These new models, which we term Multi-Functional Human Tissue Genetics, allow up to 10 alleles or more to be altered simultaneously, permitting genetic experiments with an unprecedented degree of rapidity and complexity.
Stem cell biology and differentiation
In stratified epithelia proliferative basal cells adherent to the underlying basement membrane undergo cell cycle arrest then outward migration and terminal differentiation. This process is mediated by 2 mutually exclusive programs of gene expression: 1) an undifferentiated program supporting proliferation by stem cells within the basal layer and 2) a differentiation program instructing growth arrest and differentiation-associated programmed cell death in suprabasal layers. The control of this transition from epithelial stem cell to differentiated corneocyte, which is abnormal in epidermal cancers, is not well understood. We are currently pursuing studies of the dominant signaling and gene regulatory networks that control this process, including the Ras/MAPK cascade, which is required for stem cell-mediated self-renewal and the p53 transcription factor family member, p63, which is required for epidermal differentiation.
Epigenetic regulation by histone modifying proteins and noncoding RNA
In addition to classical gene regulatory networks noted above, we have recently identified a central role for additional biologic mechanisms, namely gene regulation by chromatin regulators and by noncoding RNAs. Epigenetic control of gene expression lasts through multiple cell divisions without alterations in primary DNA sequence and can occur via mechanisms that include histone...
Publications
- Mek1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia. "Dev Cell" 2007 ; 4 615-29
- p63 regulates proliferation and differentiation of developmentally mature keratinocytes. "Genes Dev" 2006 ; 22 3185-97
- Type VII collagen is required for Ras-driven human epidermal tumorigenesis. "Science" 2005 ; 5716 1773-6
- Use of human tissue to assess the oncogenic activity of melanoma-associated mutations "Nature Genetics" 2005 : 745-749
- NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. "Nature" 2003 ; 6923 639-43
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