Laura Crisa, PhD
Metabolism, Endocrinology & Nutrition
Associate Professor of Medicine
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.
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.
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 Endocrinol 122: 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 Immunol 11:889-898, 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. Blood 94:3928-3940, 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.