• Associate Professor, Biology, School of Science and Technology, Nazarbayev University, 2012-
• Faculty member, School of Biomedical Engineering, McMaster University, 2006-
• Associate Professor, Department of Pathology & Molecular Medicine, McMaster University, 2002-.
• Scientist, Canadian Blood Services, Research & Development, Health Sciences, McMaster University, 2002-2009.
• Assistant Professor, Department of Pathology & Molecular Medicine, McMaster University, 1997-2002.
• Scholar, Bayer/MRC, Health Sciences, McMaster University, 1997-2002.
• Career Development Fellow, Canadian Red Cross Society, Health Sciences, McMaster University, 1994-1997.
• Postdoctoral Fellow, Pediatrics, McMaster University, 1992-1994.
Novel strategies to deliver genes and cells for therapeutic purposes
1) Cell encapsulation. My laboratory has had a longstanding interest in cell engineering and cell transplantation for the delivery of therapeutics. The immunoisolation of engineered cells enclosed in biocompatible polymeric semipermeable microcapsules allows the transplantation of allogeneic cells while protected from rejection. Further, it results in effective survival of the transplanted cells, and the ability to retrieve the implanted microcapsules if necessary. We have successfully applied this technology to deliver coagulation factors in hemophilic mice.
2) Nanotechnology. My laboratory has developed DNA nanoparticles for oral administration. The formulation protects DNA from degradation in the gastrointestinal tract. The treatment induces the expression of the ingested transgene in cells of the gut for local or systemic therapeutic applications. The long term objective is to make the concept of oral gene therapy a reality.
3) Immune modulation strategies. Immune responses elicited in response to administered genes and cells limit the efficacy of the therapy, increase medical costs and pose significant challenges to the management of patients. My laboratory is interested in developing novel strategies to eliminate or modulate the production of neutralizing antibodies, based on selective depletion of antigen-specific immunoglobulin and co-administration of proteins that induce antigen competition in the recipient.
1. Hortelano, G., A. Al-Hendy, F.A. Ofosu, and P.L. Chang. 1996. Delivery of human factor IX in mice by microencapsulated recombinant myoblasts: A novel approach towards allogeneic gene therapy of hemophilia B. Blood 87(12):5095-5103;
2. Orive G, Hernandez RM, Gascon AR, Calafiore R, Chang TM, Vos PD, Hortelano G, Hunkeler D, Lacik I, Shapiro AM, Pedraz JL. 2003. Cell encapsulation: Promise and progress. Nature Medicine 9(1):104-107;
3. Dhadwar S, Kiernan J, Wen J, Hortelano G. 2010. Repeated oral administration of chitosan/DNA nanoparticles delivers functional FVIII with the absence of antibodies in hemophilia A mice. Journal of Thrombosis & Haemostasis, 8(12):2743-2750.