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Dr. James R. Wright, Jr.

Dr. James R. Wright, Jr.
Professor & Head,
Department of Pathology & Laboratory Medicine
jim.wright@cls.ab.ca
Tel: (403) 770-3569
Fax: (403) 770-3788
Lab: (403) 210-3952

Area of Research - Our laboratory’s major thrust is pancreatic islet transplantation as a treatment for type I diabetes mellitus. Our current specific research interests include:

1) Methods of prolonging islet allograft and xenograft survival: Our primary approaches are methods of islet encapsulation in which the islets are protected from the immune system by a semi-perrmeable barrier with pore sizes small enough to prevent leukocytes and antibodies from engaging the graft yet large enough for insulin, glucose, oxygen, and waste products to pass through. We also study the effects of pharmacological immunosuppression, monoclonal antibody treatments, graft immunomodulation, and transplantation into immuno-privileged sites.

2) Comparative pancreatic islet physiology: Our main animal model utilizes tilapia Brockmann bodies (large anatomically discrete islet organs present in certain teleost fish) as a source of xenogeneic islets for transplantation studies. Relative to mammalian islets, tilapia islets are simple to harvest and tolerate more hypoxic conditions, such as present within encapsulation devices. When transplanted into diabetic nude mice (which cannot reject the xenografts), these islets provide long-term normoglycemia and mammalian-like glucose tolerance profiles. However, sequence differences between tilapia and human insulins might preclude using tilapia islets for clinical islet xenotransplantation. Therefore, we have produced transgenic tilapia expressing a humanized tilapia insulin gene, which we are attempting to characterize. Because we are considering the possibility of transplanting fish islets clinically, it is important to understand how they work. We are examining differences between fish and mammalian islets in vitro, in vivo, and after xenotransplantation.

3) Mechanism of graft primary non-function after intraportal islet transplantation: The standard method for clinical islet allotransplantation is to embolize the islets into the portal vein resulting in the islets distributing throughout the liver. This route of islet delivery is not possible for islet xenotransplantation as dogma states that, even in athymic nude mice that cannot reject islet xenografts, intraportally transplanted discordant islet xenografts are immediately and uniformly destroyed via Immediate Blood-Mediated Inflammatory Reaction (IBMIR), a innate inflammatory process involving the coagulation and complement cascades. We have found that islets xenografts transplanted via the portal vein are immediately destroyed in diabetic nude mice but are protected when transplanted into non-diabetic nude mice; furthermore, these intraportal islet grafts will provide long-term function if diabetes is induced as little as 3 days post-transplantation. We are currently dissecting the mechanism by which “glucose toxicity” at the time of engraftment adversely affects intraportal islet xenografts. This effect appears to be oxygen radical mediated.We are also studying alternative sites for transplanting islets.


Selected Publications

Hrytsenko O, Pohajdak B, Wright JR Jr.Production of transgenic tilapia homozygous for a humanized insulin gene. Transgenic Res. 19(2): 305-306, 2010. (Technical Update)

Hrytsenko O, Pohajdak B, Xu B-Y, Morrison CM, van Tol B, Wright JR Jr. Cloning and molecular characterization of the Glucose Transporter 1 in tilapia (Oreochromis niloticus). Gen. Comp. Endocrinol. 165(2): 293-303, 2010.

Wright JR Jr, Snowden J, Hrytsenko O, Morrison CM, and Pohajdak B. Immunohistochemical staining for tilapia and human insulin demonstrates that a tilapia transgenic for humanized insulin is a mosaic. Transgenic Res. 17(5): 991-992, 2008. (Technical Update)

Salazar-Banuelos A, Wright JR Jr, Sigalet D, and Benitez-Bribiesca L. Pancreatic islet transplantation into the bone marrow of the rat. Am. J. Surg. 195(5): 674-678, 2008.

Xu BY, Yu Y, Al Abdullah I, Kandeel F, Hering B, and Wright JR Jr. Long-term survival and function of intraportal porcine and human islets xenografts in non-diabetic nude mice. Transplant. Proc. 40(2): 584-586, 2008.

Amin H, Holst JJ, Hartman B, Wallace L, Wright JR Jr, Sigalet DL. Functional ontogeny of the proglucagon derived peptide axis in the human neonate. Pediatrics 121: e180-186, 2008.

Hrytsenko O, Wright JR Jr, Pohajdak B. Regulation of insulin gene expression and insulin production in Nile tilapia (Oreochromis niloticus). Gen. Comp. Endocrinol. 155(2): 328-340, 2008.

Hrytsenko O, Wright JR Jr, Morrison CM, Pohajdak B. Insulin expression in the brain and pituitary cells of tilapia (Oreochromis niloticus). Brain Res. 1135(1): 31-40, 2007.

Salazar A, Wright JR Jr. Islet xenotransplantation clinical trial: does histology show islet cells? Eur. J. Endocrinol. (letter). 154: 917-918, 2006.

Alexander E, Dooley KC, Pohajdak B, Wright JR Jr. Things we’ve learned from tilapia islet xenotransplantation. Gen. Com. Endocrinol. 148(2): 125-131, 2006 (Invited review). 

Al-Jazaeri A, Xu B-Y, Yang H, MacNeil D, Leventhal JR, Wright JR Jr. Effect of glucose toxicity on intraportal tilapia islet xenotransplantation in nude mice. Xenotransplantation. 12: 189-96, 2005.

Xu B-Y, Yang H, Serreze DV, MacIntosh R, Yu W,  Wright JR Jr. Rapid destruction of encapsulated islet xenografts by NOD mice is CD4 dependent & facilitated by B-cells. Transplantation. 80: 402-409, 2005.

 

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Personnel

Carol Burrows
Medical and Academic Affairs Coordinator
Carol Morrison, PhD
Research Associate
Sherry Mount
Administrative Assistant
Sze Seck
Research Technician