The current proposal represents a continuation of the candidate's research on the regulation of epidermal differentiation, with specific emphasis on the effects of polyunsaturated fatty acids. The proposal sets forth the hypothesis that specific n3 fatty acids found in fish oil can regulate and alter normal epidermal biology. Since other fatty acids of the n6 polyunsaturated family and their eicosanoid derivatives are known regulators of epidermal biology, it is reasonable to propose that the n3 fatty acid family and their unique metabolites may alter the normal progression of keratinocyte differentation by substitution for n6 fatty acids in membrane lipids, metabolic reactions, and structural components of the keratinocyte. This hypothesis will be tested by enriching cultured human neonatal keratinocytes with either eicosapentaenoic (20:5n3) or docosahexaenoic (22:6n3) acids and monitoring their proliferation and differentiation patterns, using known morphologic and biochemical markers of keratinocyte maturation. The pattern of incorporation of these fatty acids into cellular lipids as well as their leukotriene and prostaglandin metabolic products will be examined. Additionally, the preferential sequestration of n3 fatty acids to specific keratinocyte organelles will be determined. These studies should not only clarify what effect fish oil derived n3 fatty acids, now gaining popularity as dietary supplements, have on skin structure and function, but should also help to elucidate the mechanism by which these fatty acids alter epidermal biology. An RCDA would free the candidate from clinical, teaching, and administrative responsibilities within the department, enhancing the candidate's research in two ways. First, more uninterrupted time would become available for reading, writing and long-term experiments. Second, and more important, with large blocks of time available, the candidate will be able to develop new techniques necessary to establish herself as an independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Modified Research Career Development Award (K04)
Project #
5K04AR001803-04
Application #
3071382
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Rosales, J L; Isseroff, R R (1995) Increased expression of a high molecular weight (130 KD) protein kinase C isoform in a differentiation-defective ras-transfected keratinocyte line. J Cell Physiol 164:509-21
Dans, M J; Isseroff, R (1994) Inhibition of collagen lattice contraction by pentoxifylline and interferon-alpha, -beta, and -gamma. J Invest Dermatol 102:118-21
Smith, L H; Foster, C; Hitchcock, M E et al. (1993) In vitro HPV-11 infection of human foreskin. J Invest Dermatol 101:292-5
Mauro, T M; Isseroff, R R; Lasarow, R et al. (1993) Ion channels are linked to differentiation in keratinocytes. J Membr Biol 132:201-9
Winder, B S; Nourooz-Zadeh, J; Isseroff, R R et al. (1993) Properties of enzymes hydrating epoxides in human epidermis and liver. Int J Biochem 25:1291-301
Rood, P A; Haas, A F; Graves, P J et al. (1992) Low-energy helium neon laser irradiation does not alter human keratinocyte differentiation. J Invest Dermatol 99:445-8
Mauro, T M; Pappone, P A; Isseroff, R R (1990) Extracellular calcium affects the membrane currents of cultured human keratinocytes. J Cell Physiol 143:13-20