Scientific Committee

Biography

Francis J. Castellino, Ph.D., FAHA, FAAAS, is the Kleiderer-Pezold Professor of Biochemistry and Director of the W.M. Keck Center for Transgene Research at the University of Notre Dame. He received his Ph.D. from the University of Iowa and did postdoctoral work at Duke University. Dr. Castellino joined the University of Notre Dame faculty in 1970, where he remains today. He served as Dean of Science for more than 20 years and has performed research in the field of hemostasis under continuous NIH funding. The interests of the laboratory encompass the spectrum of physical biochemistry to disease models involving the crosstalk of hemostasis and inflammation, where he has published >500 peer-reviewed articles. He has served on many internal and external committees, won numerous awards, and trained over 100 graduate and undergraduate students, postdoctorals, and research fellows.

Abstract

The innate immune system plays a critical role in the pathogenicity of Streptococcal pyogenes (GAS) infections. The hemostasis, fibrinolytic, and inflammatory systems play pivotal roles in this regard. This cascade begins with the initiation of the blood coagulation system via the intrinsic (contact) pathway, which has a strong interdependence with inflammation via bradykinin release. The fibrinolytic system also plays an important role in the virulence of many GAS strains due to plasminogen binding to GAS receptors and its activation to the strong protease, plasmin, on the cell surface. This process leads to a proteolytic bacterial surface, which can assist its dissemination into deep tissue sites with concomitant development of maladies such as sepsis and necrotic fasciitis. Thus, the ability of GAS to result in more than self-limiting infections greatly depends on its conscription of host systems.