James T. Elder, M.D., Ph.D.
Associate Professor of Dermatology and Radiation Oncology (Cancer Biology)

Phone:
Fax:
E-mail:		 734-763-0355
734-763-4575
jelder@umich.edu

B.S.: Biomedical Engineering, Northwestern University
M.D. : Medical Scientist Training Program,
Yale University School of Medicine
Ph.D. : Molecular Biophysics & Biochemistry,
The Graduate School of Yale University
Post-Doctoral Fellowship: Department of Chemistry, University of California, Berkeley
Internship: Internal Medicine, University of Washington
Residency: Dermatology Fellowship, University of Washington
Fellowship: Senior Research Fellow, Dermatology, University of Michigan

Clinical Activities:

Staff, St. Joseph's Mercy Hospital, Ypsilanti, Michigan
Staff, Chelsea Community Hospital
Staff, University of Michigan Hospitals
Physician, Ann Arbor Veterans Administration Hospital

Research Interests:

Basic: Signal Transduction; Epidermal Growth and Differentiation; Chromatin Structure and Gene Regulation; Genetic Linkage Analysis

Applied: Psoriasis; Wound Healing; Nonmelanoma Skin Cancer

Dr. James T. ("J.T.") Elder is a true multidisciplinary clinician-scientist, trained in cell biology, biochemistry, and genetics as well as dermatology. In addition to running one full-service Dermatology clinic at the Veterans Administration and one at St. Joseph's Mercy Hospital every week, Dr. Elder directs a large and active laboratory, including fellow faculty, postdoctoral fellows, technicians, and students.

Research in Dr. Elder's laboratory can be classified into one of four subject areas, diverse in content and experimental approach but united in their goal of better understanding the molecular mechanisms that control the delicate balance between growth and differentiation of the epidermis. While his laboratory features an emphasis in fundamental mechanisms of gene regulation and the impact of specific genes on keratinocyte growth, differentiation, and survival, he is very interested in translating this new knowledge into improved medical care, particularly in the areas of psoriasis, wound healing, and skin cancer.

In one project, his laboratory is studying the role played by the epidermal growth factor receptor (EGFR) and related receptors as a key signaling mechanism for the early phases of epidermal wound healing, in which keratinocytes must rapidly reorganize to cover the wound, then grow rapidly to restore the normal thickness of the epidermis. Making use of EGFR knockout mice as well as a novel human skin organ culture system, Dr. Elder and colleagues are focusing on the mechanisms by which EGFR activation triggers keratinocyte migration and proliferation. Interestingly, his group has found that EGFR also tells cells where not to grow, by protecting them from programmed cell death (apoptosis).

In a second project, Dr. Elder's lab is identifying novel genes from the "epidermal differentiation complex" (EDC), a cluster of at least 25 genes involved in the control of epidermal (and, more broadly, epithelial) differentiation. They are also attempting to understand the mechanisms through which the clustered genes of the EDC are coordinately regulated during the differentiation process. In this work, Dr. Elder brings expertise gathered from his previous studies of the human hemoglobin gene cluster.

A third project in Dr. Elder's lab focuses on the product of one specific member of the EDC: a calcium-binding protein called CaN19 or S100A2. He is exploring the possible ways that this calmodulin-related protein may influence calcium-dependent epidermal differentiation by binding to and influencing the activity of specific target proteins, including nuclear transcription factors.

Finally, Dr. Elder's lab is using genetic linkage techniques to learn more about how the epidermal differentiation mechanism is perturbed in psoriasis. Their recent localization of a susceptibility determinant to a 0.4 megabase interval in the Class I region of the major histocompatibility complex (MHC) is providing an exciting new way to address this problem through positional cloning. Also, outside of the MHC, the lab has confirmed one additional psoriasis susceptibility locus on chromosome 17, as well as two promising two regions on chromosomes 16 and 20.

 

Representative Publications

  1. Deshpande R, Woods TL, Fu J, Zhang T, Elder JT
    Biochemical characterization of S100A2 in human keratinocytes: Subcellular localization, dimerization, and oxidative crosslinking. J Invest Dermatol 115: 477-485, 2000.

  2. Nair RP, Stuart P, Henseler T, Jenisch S, Chia NVC, Westphal E, Schork NJ, Kim J, Lim H W, Christophers E, Voorhees JJ, Elder J
    Localization of psoriasis susceptibility locus PSORS1 to a 60 kilobase interval telomeric to HLA-C. Am J Hum Genet 66:1833-1844, 2000.

  3. Tavakkol A, Varani J. Elder JT, Zouboulis CC
    Maintenance of human skin in organ culture: role for insulin-like growth factor-1 receptor and epidermal growth factor receptor. Arch Dermatol Res 291:643-651, 1999.

  4. Stoll SW, Elder JT
    Differential regulation of EGF-like growth factor genes in human keratinocytes. Biochem Biophys Res Commun 265: 214-221, 1999.

  5. Varani J, Kang S, Stoll S, Elder JT
    Human psoriatic skin in organ culture: similarity to normal skin exposed to exogenous growth factors and effects of an antibody to the EGF receptor. Pathobiology 66:253-259, 1998.

  6. Stoll SW, Elder JT
    Retinoid regulation of heparin-binding EGF-like growth factor gene expression in human keratinocytes and skin. Exp Dermatol 7:391-397, 1998.
  7. Stoll SW, Zhao XP, Elder J
    EGF receptor activation stimulates transcription of CaN19 (S100A2) in HaCaT keratinocytes. J Invest Dermatol 111:1092-1097, 1998.

  8. Stoll S, Benedict M, Mitra R, Hiniker A, Elder J, Nunez G
    EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL. Oncogene16(11):1493-1499, 1998.

  9. Zhao X, Elder JT
    Positional cloning of novel skin-specific genes from the human epidermal differentiation complex. Genomics 45: 250-258, 1997.

  10. Stoll S, Garner W, Elder J
    Heparin-binding ligands mediate autocrine EGF receptor activation in skin organ culture. J Clin Invest 100:1271-1281, 1997.

  11. Nair RP, Henseler T, Jenisch S, Stuart P, Bichakjian C, Lenk W, Westphal E, Guo S, Christophers E, Voorhees J, Elder J
    Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum Mol Genet 6:1349-1356, 1997.

  12. Xia L-Q, Stoll SW, Liebert M, Ethier SP, Carey T, Esclamado R, Carroll W, Johnson TM, Elder JT
    CaN19 expression in benign and malignant hyperplasias of the skin and oral mucosa: Evidence for a role in regenerative differentation. Cancer Res 57:3055-3062, 1997.

  13. Elder JT, Kaplan A, Cromie MA, Kang S, Voorhees JJ
    Retinoid induction of CRABP-II mRNA in human dermal fibroblasts: Use as a retinoid bioassay. J Invest Dermatol 106:517-521, 1996.

  14. Hardas BD, Zhao XP, Zhang J, Xia L-Q, Stoll S, Elder JT
    Assignment of psoriasin to human chromosomal band 1q21: Coordinate expression of clustered genes in psoriasis. J Invest Dermatol 106:753-758, 1996.

  15. Elder JT, Henseler T, Christophers E, Voorhees JJ, Nair RP
    The genetics of psoriasis. Arch Dermatol 130:216-224, 1994.

  16. Elder JT, Hammerberg C, Cooper KD, Kojima T, Nair RP, Ellis CN, Voorhees JJ
    Cyclosporin A rapidly inhibits epidermal cytokine expression in psoriasis lesions, but not in cytokine-stimulated cultured keratinocytes. J Invest Dermatol, 101(6):761-766, 1993.

  17. Elder JT, Cromie MA, Griffiths CEM, Chambon P, Voorhees JJ
    Stimulus-selective induction of CRABP-II mRNA: A marker for retinoic acid action in human skin. J Invest Dermatol 100:356-359, 1993.

  18. Elder JT, Sartor CI, Boman DK, Benrazavi S, Fisher GJ, Pittelkow MR
    Interleukin 6 in psoriasis: Expression and mitogenicity studies. Arch Dermatol Res 284:324-332, 1992.

  19. Klein SB, Fisher GJ, Jensen T, Mendelsohn J, Voorhees JJ, Elder JT
    Regulation of TGF-a expression in human keratinocytes: PKC-dependent and -independent pathways. J Cell Physiol 151:326-336, 1992.

  20. Astrom A, Tavakkol A, Pettersson U, Cromie M, Elder JT, Voorhees JJ
    Molecular cloning of two human cellular retinoic acid-binding proteins (CRABP). J Biol Chem 266:17662-17666, 1991.

  21. Elder JT, Fisher GJ, Zhang QY, Eisen D, Krust A, Kastner P, Chambon P, Voorhees JJ
    Retinoic acid receptor gene expression in human skin. J Invest Dermatol 96:425-433, 1991.

  22. Elder JT, Tavakkol A, Klein SB, Zeigler ME, Wicha M, Voorhees JJ
    Protooncogene expression in normal and psoriatic skin. J Invest Dermatol 94:19-25, 1990.

  23. Elder JT, Forrester WC, Thompson C, Mager D, Henthorn P, Peretz M, Papayannopoulou T, Groudine M
    Translocation of an erythroid-specific hyper-sensitive site in deletion-type hereditary persistence of fetal hemoglobin. Mol Cell Biol 10:1382-1389, 1990.

  24. Elder JT, Fisher GJ, Lindquist PB, Bennett GL, Pittelkow MR, Coffey RJ, Ellingsworth L, Derynck R, Voorhees JJ
    Overexpression of transforming growth factor a in psoriatic epidermis. Science 243:811-814, 1989.

  25. Forrester WC, Thompson C, Elder JT, Groudine M
    A developmentally stable chromatin structure in the human b-globin gene cluster. Proc Natl Acad Sci, USA 83:1359-1363, 1986.