S711 Scaife Hall
University of Pittsburgh
School of Medicine
Pittsburgh, PA 15261

Office Telephone: (412) 624-0613
Fax: (412) 628-1916
E-mail: hshiraha@imap.pitt.edu

• Epidermal growth factor receptor signaling and cell motility.
• EGFR-mediated motility signaling in fibroblasts is negatively affected by inhibitory signals during wound repair and by aging.
• Anti-inflammatory chemokine IP-10 inhibits motility but not proliferation, and this occurs downstream of PLC? and MAP kinase signaling. EGFR-mediated activation of calpain and subsequent cell-substratum de-adhesion is inhibited by IP-10 signaling through cAMP-PKA signaling pathway.
• During aging, both motility and mitogenesis are decreased, with the EGF response being lost in near senescent dermal fibroblasts. This is a consequence of reduced levels of EGFR due to markedly reduced transcription, expression of 'young' levels of EGFR restores the EGF responsiveness.

Japan scholarship foundation first category grantee 1992-1996

1. Shiraha H., Koide N., Hada H., Ujike K., Nakamura M., Shinji T., Gotoh S., Tsuji T. Improvement of serum amino acid profile in hepatic failure with the bio-artificial liver using multicellular hepatocyte spheroids. Biotechnologies and Bioengineering 50; 416-421, 1996
2. Shiraha H., Glading A., Gupta K., Wells A. IP-10 inhibits epidermal growth factor-induced motility by decreasing epidermal growth factor receptor-mediated calpain activity. Journal of Cell Biology 146(1); 243-253, 1999
3. Shiraha H., Drabik K., Gupta K., and Wells A. Aging fibroblasts present reduced epidermal growth factor (EGF) responsiveness due to preferential loss of EGF receptors. Journal of Biological Chemistry. 275(25); 19343-19351, 2000