Our Research: Faculty/Research Laboratories

Laura Crisa MD, PhD

Associate Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition

Email Address: lcrisa@u.washington.edu

Division of Metabolism, Endocrinology and Nutrition Website:  http://depts.washington.edu/metab/

Laura Crisa

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, Salomon DR. Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts.  J Exp Med 186:289-298, 1997.

Crisa L, Cirulli V, Smith KA, Ellisman MH, Torbett BE, Salomon DR. Human Cord blood progenitors sustain thymic T cell development and a novel form of angiogenesis. Blood 94:3928-3940, 1999.

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 104:2010-2019, 2004.

Cirulli V, Zalatan J, McMaster M, Prinsen R, Salomon DR, Ricordi C, Torbett BE, Meda P, Crisa L. The class I HLA repertoire of pancreatic islets comprises the non-classical class Ib antigen HLA-G. Diabetes 55:1214-1222, 2006.

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 57:2402-2412, 2008.

  • Di Mario U, Dotta F, Crisa L, Anastasi E, Andreani D, Dib S, Eisenbarth GS. Circulating anti-immunoglobulin antibodies in recent onset Type I diabetic patients. Diabetes 37: 462-466, 1986.

    Di Mario U, Crisa L, Anastasi E, Contreas G, Andreani D, Raponi MP, Napoleone E, Candela A, Vela M, Campea L. Anti-goat immunoglobulin antibodies in diabetic children at diagnosis and follow up: comparison with islet cell antibodies and other autoantibodies. Acta Endocrinol 120: 326-330, 1989.

    Di Mario U, Perfetti R, Anastasi E, Contreas G, Crisa L, Tiberti C, Amendolea MA, Masala C. Autoantibodies to insulin do appear in non-diabetic patients with autoimmune disorders: comparison with anti-immunoglobulin antibodies and other phenomena. Acta Endocrinol122: 203-308, 1990.

    Crisa L, Greiner DL, Mordes JP, MacDonald RG, Handler ES, Czech MP, Rossini AA. Biochemical studies of RT6 alloantigens in BB/Wor and normal rats. Evidence for intact unexpressed RT6a structural gene in diabetes prone BB rats. Diabetes 39:1279-1288, 1990.

    Vardi P, Crisa L, Jackson RA. Predictive value of intravenous glucose tolerance test insulin secretion less than or greater than the first percentile in islet antibodies positive relatives of Type 1 (insulin-dependent) diabetic patients.  Diabetologia 34:94-102, 1991.

    Crisa L, Sarkar P, Haag F, Kock-Nolte F, Thiele HG, Handler ES, Mordes JP, Rossini AA, Greiner DL: “An RT6a gene is transcribed and translated in the lymphopenic diabetes prone BB rat.”   Diabetes 42:688-695, 1993.

    Sarkar P, Crisa L, McKeever U, Bortell R, Handler ES, Mordes JP, Waite D, Schoenbaum A, Haag F, Koch-Nolte F, Greiner DL, Rossini AA. Loss of RT6 message and T cells after thymectomy of diabetes prone BB rats.   Autoimmunity 18:15-22, 1994.

    Crisa L, Cirulli V, Ellisman M, Ishii JK, Elices MJ, Salomon DR. Cell adhesion and migration is regulated at distinct stages of thymic T cell development: the role of fibronectin, VLA4 and VLA5.  J Exp Med 184: 215-228, 1996.

    Todd SC, Lipps SG, Crisa L, Salomon DR, Tsoukas CD. CD81 expressed on human thymocytes mediates integrin activation and IL2 proliferation.   J Exp Med 184:2055-2060, 1996.

    Salomon DR, Crisa L, Mojcik CF, Ishii J, Klier G, Shevach EM. Human thymic epithelial cells express vascular cell adhesion molecule-1 (VCAM-1) and bind thymocytes via the integrin a4b.   Blood 89:2461-2471, 1997.

    Crisa L, McMaster M, Ishii JK, Fisher SJ, Salomon DR. Identification of a thymic epithelial cell subset sharing expression of the class Ib HLA-G molecule with fetal trophoblasts.  J Exp Med 186:289-298, 1997.

    Cirulli V, Crisa L, Beattie GM, Mally MI, Lopez AD, Fannon A, Ptasznik A, Inverardi  L,  Ricordi C, Deerinck T, Ellisman M,  Reisfeld RA, Hayek A. KSA antigen (Ep-CAM) mediates cell-cell adhesion of pancreatic epithelial cells: morphoregulatory roles in pancreatic islet development.  J Cell Biol 140:1519-1534, 1998.

    Mallet V, Blaschitz A, Crisa L, Schmitt C, Fournel S, King A, Loke YW, Dohr G, Le Bouteiller P. HLA-G in the human thymus: a subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein.   Int Immunol11:889-898, 1999.

    Crisa L, Cirulli V, Smith KA, Ellisman MH, Torbett BE, Salomon DR. Human Cord blood progenitors sustain thymic T cell development and a novel form of angiogenesis. Blood94:3928-3940, 1999.

    Kikuchi T, Ichimiya S, Kojima T, Crisa L, Koshiba S, Tonooka A, Van Der Saag PT, Yokoyama S, Sato N. Expression profiles and functional implications of p53-like transcription factors in thymic epithelial cell subtypes.  Int Immunol 16:831-841, 2004.

    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 104:2010-2019, 2004.

    Cirulli V, Zalatan J, McMaster M, Prinsen R, Salomon DR, Ricordi C, Torbett BE, Meda P, Crisa L.   The class I HLA repertoire of pancreatic islets comprises the non-classical class Ib antigen HLA-G.   Diabetes 55:1214-1222, 2006.

    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 57:2402-2412, 2008.

    Crisa L. Pancreatic islet transplants and IDO: when starving the enemy does you good.Diabetes 2010. In Press.

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