EDUCATION
Ph.D. in molecular genetics. Department of Biology, University of Wollongong, Wollongong, Australia
M.Sc. in bacterial genetics. Department of Microbiology, University of the Witwatersrand, Johannesburg, South Africa
B.Sc. (Hons.), University of The Basque Country, Bilbao, Spain
POSITIONS
• Full Professor, Biology, School of Science and Technology, Nazarbayev University, 2016-
• Acting Chair, Department of Biology, School of Science and Technology, Nazarbayev University, 2015-2017
• Associate Professor, Biology, School of Science and Technology, Nazarbayev University, 2012-2016
• 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.
RESEARCH INTERESTS
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.
REPRESENTATIVE PUBLICATIONS
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.
Fibronectin-Alginate microcapsules improve cell viability and protein secretion of encapsulated Factor IX-engineered human mesenchymal stromal cellsSayyar, B., Dodd, M., Marquez-Curtis, L., Janowska-Wieczorek, A., Hortelano, G.,
2015 In : Artificial Cells, Nanomedicine and Biotechnology. 43, 5, p. 318-327
Sustained expression of coagulation factor IX by modified cord blood-derived mesenchymal stromal cellsDodd, M., Marquez-Curtis, L., Janowska-Wieczorek, A., Hortelano, G.,
2014 In : Journal of Gene Medicine. 16, 5-6, p. 131-142
Cell-matrix Interactions of Factor IX (FIX)-engineered human mesenchymal stromal cells encapsulated in RGD-alginate vs. Fibrinogen-alginate microcapsulesSayyar, B., Dodd, M., Marquez-Curtis, L., Janowska-Wieczorek, A., Hortelano, G.,
2014 In : Artificial Cells, Nanomedicine and Biotechnology. 42, 2, p. 102-109
Strategies for ocular siRNA delivery: Potential and limitations of non-viral nanocarriersThakur, A., Fitzpatrick, S., Zaman, A., Kugathasan, K., Muirhead, B., Hortelano, G., Sheardown, H.,
2012 In : Journal of Biological Engineering. 6,
Encapsulated engineered myoblasts can cure Hurler syndrome: Preclinical experiments in the mouse modelPiller Puicher, E., Tomanin, R., Salvalaio, M., Friso, A., Hortelano, G., Marin, O., Scarpa, M.,
2012 In : Gene Therapy. 19, 4, p. 355-364
Single-colour flow cytometric assay to determine NK cell-mediated cytotoxicity and viability against non-adherent human tumor cellsThakur, A., Zaman, A., Hummel, J., Jones, K., Hortelano, G.,
2012 In : Biotechnology Letters. 34, 3, p. 447-453
Encapsulation of factor IX-engineered mesenchymal stem cells in fibrinogen-alginate microcapsules enhances their viability and transgene secretionSayyar, B., Dodd, M., Wen, J., Ma, S., Marquez-Curtis, L., Janowska-Wieczorek, A., Hortelano, G.,
2012 In : Journal of Tissue Engineering. 3, 1, p. 1-12
Repeated oral administration of chitosan/DNA nanoparticles delivers functional FVIII with the absence of antibodies in hemophilia A miceDhadwar, S., Kiernan, J., Wen, J., Hortelano, G.,
2010 In : Journal of Thrombosis and Haemostasis. 8, 12, p. 2743-2750
Monkey business for hemophilia managementHortelano, G.,
2010 In : Thrombosis Research. 126, 5, p. 365-366
Therapeutic applications of cell microencapsulation. Foreword.Hortelano, G.,
2010 In : Advances in Experimental Medicine and Biology. 670,
Characterization of viability and proliferation of alginate-poly-L-lysine- alginate encapsulated myoblasts using flow cytometryThakur, A., Sengupta, R., Matsui, H., Lillicrap, D., Jones, K., Hortelano, G.,
2010 In : Journal of Biomedical Materials Research - Part B Applied Biomaterials. 94, 2, p. 296-304
Advances in Experimental Medicine and Biology: ForewordHortelano, G.,
2010 In : Advances in Experimental Medicine and Biology. 670,
Early intraplatelet signaling enhances the release of human platelet PAR-1 and -4 amino-terminal peptides in response to thrombinOfosu, F., Dewar, L., Song, Y., Cedrone, A., Hortelano, G., Craven, S.,
2009 In : Biochemistry. 48, 7, p. 1562-1572
Factors that contribute to the immmunogenicity of therapeutic recombinant human proteinsMukovozov, I., Sabljic, T., Hortelano, G., Ofosu, F.,
2008 In : Thrombosis and Haemostasis. 99, 5, p. 874-882
Encapsulated human primary myoblasts deliver functional hFIX in hemophilic miceWen, J., Xu, N., Li, A., Bourgeois, J., Ofosu, F., Hortelano, G.,
2007 In : Journal of Gene Medicine. 9, 11, p. 1002-1010
Transplants for HemophiliaGómez-Vargas, A., Hortelano, G.,
2007 Cellular Transplantation. Elsevier, p. 187-203
Sustained and therapeutic levels of human factor IX in hemophilia B mice implanted with microcapsules: Key role of encapsulated cellsWen, J., Vargas, A., Ofosu, F., Hortelano, G.,
2006 In : Journal of Gene Medicine. 8, 3, p. 362-369
An important role for the activation peptide domain in controlling factor IX levels in the blood of haemophilia B miceBegbie, M., Mamdani, A., Gataiance, S., Eltringham-Smith, L., Bhakta, V., Hortelano, G., Sheffield, W.,
2005 In : Thrombosis and Haemostasis. 94, 6, p. 1138-1147
Reduction of GAG storage in MPS II mouse model following implantation on encapsulated recombinant myoblastsFriso, A., Tomanin, R., Alba, S., Gasparotto, N., Puicher, E., Fusco, M., Hortelano, G., Muenzer, J., Marin, O., Zacchello, F., Scarpa, M.,
2005 In : Journal of Gene Medicine. 7, 11, p. 1482-1491
Continuous antigenic stimulation system (CASS) as a new immunization strategyGomez-Vargas, A., Rosenthal, K., McDermott, M., Hortelano, G.,
2004 In : Vaccine. 22, 29-30, p. 3902-3910
Effects of genetic fusion of factor IX to albumin on in vivo clearance in mice and rabbitsSheffield, W., Mamdani, A., Hortelano, G., Gataiance, S., Eltringham-Smith, L., Begbie, M., Leyva, R., Liaw, P., Ofosu, F.,
2004 In : British Journal of Haematology. 126, 4, p. 565-573
Nonviral gene therapy approaches to hemophiliaGómez-Vargas, A., Hortelano, G.,
2004 In : Seminars in Thrombosis and Hemostasis. 30, 2, p. 197-204
History, challenges and perspectives of cell microencapsulationOrive, G., Hernández, R., Rodríguez Gascón, A., Calafiore, R., Chang, T., De Vos, P., Hortelano, G., Hunkeler, D., Lacík, I., Pedraz, J.,
2004 In : Trends in Biotechnology. 22, 2, p. 87-92
Cell encapsulation: Promise and progressOrive, G., Hernández, R., Gascón, A., Calafiore, R., Chang, T., De Vos, P., Hortelano, G., Hunkeler, D., Lacík, I., Shapiro, A., Pedraz, J.,
2003 In : Nature Medicine. 9, 1, p. 104-107
Polymer-encapsulated engineered adult mesenchymal stem cells secrete exogenously regulated rhBMP-2, and induce osteogenic and angiogenic tissue formationZilberman, Y., Turgeman, G., Pelled, G., Xu, N., Moutsatsos, I., Hortelano, G., Gazit, D.,
2002 In : Polymers for Advanced Technologies. 13, 10-12, p. 863-870
Therapeutic levels of human Factor VIII in mice implanted with encapsulated cells: Potential for gene therapy of haemophilia AGarcía-Martín, C., Chuah, M., Van Damme, A., Robinson, K., Vanzieleghem, B., Saint-Remy, J., Gallardo, D., Ofosu, F., Vandendriessche, T., Hortelano, G.,
2002 In : Journal of Gene Medicine. 4, 2, p. 215-223
Non-viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome)Tomanin, R., Friso, A., Alba, S., Piller Puicher, E., Mennuni, C., La Monica, N., Hortelano, G., Zacchello, F., Scarpa, M.,
2002 In : Acta Paediatrica, International Journal of Paediatrics, Supplement. 91, 439, p. 100-104
Sustained and therapeutic delivery of factor IX in nude haemophilia B mice by encapsulated C2C12 myoblasts: Concurrent tumourigenesisHortelano, G., Wang, L., Xu, N., Ofosu, F.,
2001 In : Haemophilia. 7, 2, p. 207-214
Gene therapy for hemophiliaHortelano, G., Chang, P.,
2000 In : Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. 28, 1, p. 1-24
Therapeutic approaches for haemophiliaHortelano, G., Ofosu, F.,
2000 In : Expert Opinion on Therapeutic Patents. 10, 6, p. 929-938
Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factorSpringer, M., Hortelano, G., Bouley, D., Wong, J., Kraft, P., Blau, H.,
2000 In : Journal of Gene Medicine. 2, 4, p. 279-288
Persistent delivery of factor IX in mice: Gene therapy for hemophilia using implantable microcapsulesHortelano, G., Xu, N., Vandenberg, A., Solera, J., Chang, P., Ofosu, F.,
1999 In : Human Gene Therapy. 10, 8, p. 1281-1288
The in vivo delivery of heterologous proteins by microencapsulated recombinant cellsChang, P., Van Raamsdonk, J., Hortelano, G., Barsoum, S., MacDonald, N., Stockley, T.,
1999 In : Trends in Biotechnology. 17, 2, p. 78-83
Encapsulation of various recombinant mammalian cell types in different alginate microcapsulesPeirone, M., Ross, C., Hortelano, G., Brash, J., Chang, P.,
1998 In : Journal of Biomedical Materials Research. 42, 4, p. 587-596
Permeability of alginate microcapsules to secretory recombinant gene productsAwrey, D., Tse, M., Hortelano, G., Chang, P.,
1996 In : Biotechnology and Bioengineering. 52, 4, p. 472-484
Delivery of human factor IX in mice by encapsulated recombinant myoblasts: A novel approach towards allogeneic gene therapy of hemophilia BHortelano, G., Al-Hendy, A., Ofosu, F., Chang, P.,
1996 In : Blood. 87, 12, p. 5095-5103
Growth retardation - An unexpected outcome from growth hormone gene therapy in normal mice with microencapsulated myoblastsAl-Hendy, A., Hortelano, G., Tannenbaum, G., Chang, P.,
1996 In : Human Gene Therapy. 7, 1, p. 61-70
Correction of the growth defect in dwarf mice with nonautologous microencapsulated myoblasts - An alternate approach to somatic gene therapyAl-Hendy, A., Hortelano, G., Tannenbaum, G., Chang, P.,
1995 In : Human Gene Therapy. 6, 2, p. 165-175
Growth of recombinant fibroblasts in alginate microcapsulesChang, P., Hortelano, G., Tse, M., Awrey, D.,
1994 In : Biotechnology and Bioengineering. 43, 10, p. 925-933