Albany Medical College, USA
Paul J. Higgins received his Ph.D. degree in molecular biology from New York University in 1976. He joined the faculty of the Memorial Sloan-Kettering Cancer Center and the Cornell University School of Medicine in 1977, where he was a member in the Cell Biology/Genetics and Molecular Biology/Virology Programs. Dr. Higgins is currently a Professor and Director of the Center for Cell Biology and Cancer Research at the Albany Medical College in Albany, New York. He was the founding Vice President of the Albany Research Institute (ARI) and currently serves on the ARI Board of Directors. He has served as Chairman of National Institutes of Health and Department of Defense Review Panels, is a member of a number of federal and international study sections and received several prestigious awards including the Moyer Award and, most recently, the 2008 Excellence Award in Molecular Medicine. Dr. Higgins is a member of several journal editorial boards, edited books on cancer biology, and published more than 200 peer-reviewed scientific papers.
Molecular genetic studies in Dr. Higgins laboratory identified the mammalian SERPINE1 gene and the SERPIN family as key elements in the regulation of cell shape, motility, growth control and tissue invasion. Expression of the SERPINE1 gene is controlled in both proliferation- and differentiation-dependent fashions by specific growth factors via Src/MAP kinase/rho-mediated signal transduction pathways. Growth factors of the TGF-ß and EGF families independently trans-activate the SERPINE1 gene by means of distinct but cooperating signaling pathways that utilize stimulus-specific transcriptional control mechanisms. The SERPINE1 gene is regulated in a growth state-dependent fashion by the MYC/SMAD/USF/ TFE3 family of transcriptional activators that recognize specific promoter target sequences (E box motifs) to effect gene silencing or inducible expression. SERPINE1 transcription in normal cells is relatively low but rapidly induced in emergency conditions such as tissue injury and wound repair under conditions necessitating cell growth, migration and extracellular matrix remodeling. In human cancers, SERPINE1 functions as a tumor metastasis/pro-invasive gene, a poor prognosis biomarker and is a critical element in disease progression. Studies in PAI-1 null mice indicate that PAI-1 expression is required for normal as well as pathologic angiogenesis, tumor invasion and vascular network stability. Current investigations in the laboratory bridge two major research themes (vascular biology/angiogenesis and tumor growth/ metastasis) with an emphasis on SERPINE1 involvement and development of molecular genetic therapies for vascular and neoplastic diseases. Present work focuses on analysis of the SERPINE1 signal transduction pathway, clarifying molecular mechanisms underlying growth state-associated transcriptional control, definition of gene structure, and elucidating the role of SERPINE1 in cell growth regulation, tissue fibrosis, senescence, angiogenesis and aging-related diseases.