Laura Crisa MD, PhD
Title:
Associate Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition
Email Address:
Background:
Laura Crisa received her MD from the University of Rome in Italy in 1986, Board Certification in Endocrinology and Metabolism in 1989, and PhD in Immunology in 1992. Soon after her medical training, she left Italy to join the laboratory of Dr Aldo Rossini, at the University of Massachussets, Boston, to train as a post-doctoral fellow in the field of Immunology and animal models of Type 1 Diabetes. In 1994 she moved to the Scripps Research Institute, in La Jolla, California, as Senior Research Associate to train further in hemopoiesis and vascular biology, as applied to the biology of pancreatic islet transplantation. At the Scripps Research Institute she was appointed to the faculty in 2002. In 2009 she was recruited as Associate Professor to the Diabetes and Obesity Center of Excellence and the Institute of Stem cell and Regenerative Medicine, both at the University of Washington.
Dr. Crisa serves on study sections in immunology and vascular biology at the American Heart Association, Juvenile Diabetes Research Foundation, and NIH.
Focus:
Immune recognition of major hystocompatibility (MHC) antigens on tissue transplants is the primary barrier to allografts acceptance. There are, however, certain Class I MHC antigens that can trigger regulatory immune responses. This is the case of human HLA-G. There is extremely low polymorphism of HLA-G in the human population and high expression levels of this molecule on the trophoblast, the fetal tissue at the maternal-fetal interface, has been shown to be involved in the down-regulation of cytotoxic NK and T cell immune responses. Work in Dr. Crisa’s laboratory has shown that this unique HLA molecule is also expressed in a subset of human thymic epithelial cells and in pancreatic islets suggesting that thymic education and peripheral presentation of this HLA determinant may also sustain immunoregulatory mechanisms in post-natal life. To address this possibility, SCID mouse models reconstituted with a human immune system and transgenic models are used to determine whether engineering high levels of HLA-G expression in thymic and islet tissues can be used as a strategy to modify human alloreactive T cell repertoires and prevent transplant rejection.
Angiogenesis and self-containment of local inflammatory responses are also critical to transplant engraftment. A second major focus of Dr. Crisa’s research program is to define the developmental requirements and functional characteristics of endothelial cell progenitors of bone-marrow origin, a cell type selectively recruited at sites of tissue repair. Specifically, cellular and molecular pathways activated by bone marrow-derived vascular cells capable of delivering islet tissue survival/proliferative/differentiative signals and/or modifying innate immune responses, are the focus of this line of research. Knowledge gained from this research may help to define the transplant microenvironment and specific signaling pathways supporting engraftment of islet tissues and/or their progenitors.
Dr. Crisa’s research has been and/or is currently supported by the National Institute of Health, Juvenile Diabetes Foundation, and American Heart Association.
Representative Publications:
Crisa L, McMaster M, Ishii JK, Fisher SJ, and Salomon DR: “Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts.” J. Exp. Med. (1997) 186:289-298.
Crisa L, Cirulli V, Smith KA, Ellisman MH, Torbett BE, and Salomon DR: “Human Cord blood progenitors sustain thymic T cell development and a novel form of angiogenesis.“ Blood (1999) 94:3928-3940.
Hildbrand P, Cirulli V, Prinsen RC, Smith KA, Torbett BE, Salomon DR, Crisa L:
“The role of angiopoietins in the development of endothelial cells from cord blood CD34+ progenitors.” Blood (2004) 104 (7): 2010-2019.
Cirulli V, Zalatan J, McMaster M, Prinsen R, Salomon DR, Ricordi C, Torbett BE, Meda P and Crisa L: “The class I HLA repertoire of pancreatic islets comprises the non-classical class Ib antigen HLA-G”. Diabetes (2006) 55:1214-1222.
Miller R, Cirulli V, Diaferia GR, Ninniri S, Hardiman G Torbett BE, Benezra R, & Crisa L:
“Switching-on survival and repair response programs by bone marrow-derived vasculogenic cells”. Diabetes (2008) 57(9):2402-2412.
Current Collaborations:
Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Vincenzo Cirulli, MD, PhD
Alan Chait, MD
Mike Schwartz, MD
Ian Sweet, PhD
Outside of the Diabetes and Obesity Center of Excellence
Anthony Blau, MD, Institute for Stem Cell and Regenerative Medicine (ISCRM), University of Washington, Seattle, WA
Marshall Horwitz, PhD, ISCRM, University of Washington, Seattle, WA
Randall Moon, PhD, ISCRM, University of Washington, Seattle, WA
Jerry Nepom, MD, PhD, Benaroya Research Institute, Seattle, WA
Bruce Torbett, The Scripps Research Institute, La Jolla, CA
Lab Members:
Linsey McLennan, BS