Our Science – Katz Website

Stephen I. Katz, M.D., Ph.D.

Dermatology Branch Senior Investigator Building 10, Room 12N238 NCI-Bethesda Bethesda, MD 20892 Phone:   301-496-2481 Fax:   301-496-5370 E-Mail:   katzs@mail.nih.gov

Biography

Dr. Katz received his M.D. from Tulane University Medical School in 1966. He trained in dermatology at the University of Miami between 1967 and 1970. He then earned a Ph.D. in immunology from the University of London in 1974. He has been a member of many scientific advisory and editorial boards and currently serves as director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Research

Immunopathologic Mechanisms Involved in Inflammatory and Neoplastic Skin Diseases

Our research is focused on the skin immune system - how it functions in the generation and perpetuation of skin and systemic immune responses and how its constituents, keratinocytes and Langerhans cells, function in normal immune surveillance and in inflammatory and infectious diseases. Allergic contact dermatitis is used as the paradigm for immunological, inflammatory, infectious, and neoplastic diseases of the skin. Specific aims include the following:

- Study of the cytokine response profile during both the sensitization and elicitation phases of allergic contact sensitivity. We have studied the very earliest events (during sensitization) that occur in allergic contact dermatitis. Within 24 hrs after exposure of epidermis to haptens, there is 'activation' of Langerhans cells, as demonstrated by their expressing greatly increased amounts of class II MHC on their surfaces and becoming much more potent antigen-presenting cells. There is an almost immediate upregulation of IL-1beta mRNA from Langerhans cells after hapten application and later an upregulation of IL-10 mRNA by keratinocytes. We are also studying the effects of UV radiation on the expression of cytokine mRNA and have found that even small amounts of UVB enhance expression of IL-10 and IL-12 but inhibit IL-15, which is constitutively seen in human skin. These cytokines exert functional effects on the skin, both in vivo and in vitro. We have more recently focused our studies on understanding the relative contributions of various cell types in cellular infiltrates during the elicitation phase of contact sensitivity. Using semiquantitative RT-PCR and functional studies, we found that IL-4 downregulates contact sensitivity reactions. These studies have been validated using anti-IL-4 mAb, and using mice with genetic disruptions in CD28-B7 signaling.


- Study of the role of epidermal components in the maintenance of tolerance to protein and self antigens. We have developed a model system whereby keratinocytes of transgenic mice produce ovalbumin under the control of a K14 promoter. The skin of these mice is used as a target for T cells that are obtained from OT-I and OT-II mice that are transgenic for a TCR recognizing either ovalbumin peptides in association with class I MHC or class II MHC molecules, respectively. We have also crossed the K14-ovalbumin transgenic mice with the OT-I mice and have found that the T cells with a TCR that recognizes ovalbumin peptides is depleted. The focus of our current studies is to identify the mechanisms for this deletion and to try to modulate these immunological responses.

This page was last updated on 6/11/2008.