James Elder, MD/PhD Biography
 

Dr. Elder received his MD and PhD degrees from Yale University, followed by dermatology residency at the University of Washington.  His training there included a research fellowship at the Fred Hutchinson Cancer Research Center, where he studied mechanisms of gene regulation with Dr. Mark Groudine.  In 1986, he pursued a senior fellowship in dermatology at the University of Michigan, joining their faculty in 1988.

Dr. Elder and his colleagues have focused on a genetic approach to understanding the causes of psoriasis and psoriatic arthritis. He reported a genome-wide linkage scan for psoriasis in 1997, identified genome-wide significant linkage to the MHC Class I region in 1998, and mapped the MHC determinant to the vicinity of HLA-C in 2000.  Last year, his group showed  that the only two genes that present alleles unique to the disease chromosomes are HLA-C (HLA-Cw6 allele) and corneodesmosin (CDSN*TTC allele).  By typing these two genes in over 2,500 subjects, they showed that individuals retaining HLA-Cw6 but lacking CDSN*TTC were significantly associated with psoriasis, whereas those retaining CDSN*TTC but lacking HLA-Cw6 were not associated.  With colleagues at the U-M and other institutions, he is conducting a genome-wide association scan of psoriasis as part of the Genetic Association Information Network (GAIN).

Psoriatic lesions display remarkable epidermal hyperplasia, which is dependent upon the presence of activated immunocytes. Dr. Elder and his colleagues are also interested in the mechanisms controlling keratinocyte proliferation in psoriasis. Shortly after joining the U-M faculty, Dr. Elder demonstrated overexpression of the epidermal growth factor receptor (EGFR) ligand TGF-alpha in psoriatic lesions.  In subsequent years, this observation has been extended to multiple members of the EGFR ligand family.  Dr. Elder has identified amphiregulin (AR) as the key ligand, EGFR as the key receptor, and ERK as a key downstream mediator of autocrine proliferation in human keratinocytes.  Mice engineered to constitutively overexpress amphiregulin develop a psoriasis-like rash and arthritis, but eventually die as a result of massive inflammation. To avoid the lethality associated with this transgene, Dr. Elder is generating a transgenic mouse that conditionally overexpresses amphiregulin in the skin.  He also uses cultured keratinocytes, skin organ culture, and a SCID mouse-human skin xenograft system to investigate the role of ErbB ligands in the generation of epidermal hyperplasia and inflammation in psoriasis.