The proposed Program Project participants at the San Francisco VAMC represent workers from several medical disciplines who are focusing their divergent scientific backgrounds on the study of epidermal function in relation to growth and differentiation, utilizing cultured human keratinocytes in a series of collaborative efforts. Keratinocytes serve as a superb model for the vectorial differentiation of epithelial structures. They are metabolically highly active, and exhibit a range of previously-unappreciated functions, and are available in large quantities, as homogeneous, cloned cell populations. Furthermore, their growth and differentiation in vitro can be manipulated in a variety of systems and assessed by distinctive morphological and biochemical markers. Already, several of the investigators have found dramatic changes in metabolism in relation to differentiation. This program project therefore represents a continuation and amalgamation of sevral interdependent research programs into a formalized, co-operative effort. Drs. Bikle and Pillai will study the metabolism of vitamin D and other cytokines in relation to keratinocyte differentiation, utilizing normal keratinocytes as well as aseries of squamous cell carcinoma cell lines that exhibit distinctive phenotypes. Dr. Boyer will study enzyme systems that metabolize exogenous drugs and chemicals in relation to keratinocyte differentiation. Drs. Elias, Monger and Williams will study the relationship of shingolipid metabolism to differentiation. Drs. Goldyne and Williams will study keratinocyte-fibroblast interactions addressing how keratinocyte interleukin I and fibroblast eicosanoids may regulate keratinocyte growth and differentiation. Dr. Grayson will determine how a recently identified family of hydrophobic, membrane proteolipids may regulate keratinocyte differentiation. Each principal investigator will rely on the expertise of the other project participants in order to enhance the productivity, breadth, and depth of his/her project, and the group as a whole will benefit from weekly research meetings, the in-put of an outside research advisory group, and an outside visitor/speaker program. The proposed program project thus represents a logical extension of our on-going research efforts into a more formalized, cohesive interaction that should produce importan new insights into epidermal function in relation to differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR039448-02
Application #
3092421
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1988-07-15
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling et al. (2015) Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer. J Steroid Biochem Mol Biol 148:47-51
Bikle, Daniel D (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319-29
Bikle, Daniel D (2014) Vitamin D and cancer: the promise not yet fulfilled. Endocrine 46:29-38
Bikle, Daniel D (2014) The vitamin D receptor: a tumor suppressor in skin. Adv Exp Med Biol 810:282-302
Tu, Chia-Ling; Bikle, Daniel D (2013) Role of the calcium-sensing receptor in calcium regulation of epidermal differentiation and function. Best Pract Res Clin Endocrinol Metab 27:415-27
Jiang, Yan J; Kim, Peggy; Uchida, Yoshikazu et al. (2013) Ceramides stimulate caspase-14 expression in human keratinocytes. Exp Dermatol 22:113-8
Bikle, Daniel D (2012) Vitamin D and the skin: Physiology and pathophysiology. Rev Endocr Metab Disord 13:3-19
Bourguignon, L Y W; Earle, C; Wong, G et al. (2012) Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene 31:149-60
Tu, Chia-Ling; Crumrine, Debra A; Man, Mao-Qiang et al. (2012) Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol 132:2350-2359

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