Clinical ProfessorSenior Scientist, Canadian Blood ServicesAssociate Director for Intellectual Property and Business Development, Canadian Blood Services
Dr. Scott’s laboratory is primarily focused on three primary areas of research: 1) investigation of the potential therapeutic use of “immunocamouflaged” cells/tissues in transfusion and transplantation medicine; 2) prevention of viral invasion via viral inactivation and target cell modification via immunocamouflage; and 3) examining whether the intraerythrocytic chelation and redox-inactivation of the hemoglobin-derived heme and iron present in the sickle and thalassemic RBC can slow/prevent premature red cell destruction.
Immunocamouflage of foreign cells and tissues is accomplished via the covalent modification of the cell membrane with nonimmunogenic materials such as methoxypoly(ethylene glycol). This nonimmunogenic barrier prevents the recognition of antigenic sites on the cell membrane by preexisting antibodies –hence preventing immunological rejection – and significantly diminishes the immunogenicity of the foreign cellular epitopes. Ongoing projects within the laboratory include the modification of red blood cells to prevent alloimmunization in the chronically transfused (e.g., sickle cell, thalassemic, autoimmune hemolytic anemia) patient; the prevention of graft versus host disease via lymphocyte modification; and the modification of pancreatic islets for tissue transplantation in diabetes.
Immunocamouflage also has application in the inactivation of viruses and/or prevention of viral infections. Studies in Dr. Scott’s laboratory have demonstrated the utility of the immunocamouflage technique in inactivation viruses contained in blood products by preventing normal cellular invasion. Similarly, the immunocamouflage of the target cells of viruses has also proven effective in preventing viral invasion and infection. The utility of this technology towards blood borne and respiratory (e.g., Rhinoviruses) viruses are actively under investigation.
Additional research in Dr. Scott’s laboratory is directed towards determining whether the intraerythrocytic chelation and redox-inactivation of the hemoglobin-derived heme and iron present in the sickle and thalassemic RBC may significantly delay its premature destruction. Previous studies by this laboratory have demonstrated that the basic pathophysiology of the sickle and thalassemic RBC is Media Roomted by a self-propagating, self-amplifying redox reaction initiated by the initial autoxidation of the sickle hemoglobin or unpaired a and b hemoglobin chains. Subsequent glutathione-driven, iron-Media Roomted, oxidative events degrade additional hemoglobin (releasing more heme/Fe) as well as other cellular components leading to significant functional and structural changes. It is hypothesized that a modest prolongation of the life span of the thalassemic erythrocyte may improve the “effective” erythropoiesis (i.e., hematocrit, reticulocyte count) such that the need for transfusion therapy may be obviated in a significant segment of the thalassemic population.
Ph.D. 1988 University of Minnesota, Pathobiology (Pathology and Laboratory Medicine)
- Chapanian R, Constantinescu I, Brooks DE, Scott MD, Kizhakkedathu J. Antigens protected functional red blood cells by the membrane grafting of compact hyperbranched polyglycerols. J Vis Exp. 2013 Jan 2;(71).
- Chapanian R, Constantinescu I, Rossi NA, Medvedev N, Brooks DE, Scott MD, Kizhakkedathu JN. Influence of polymer architecture on antigens camouflage, CD47 protection and complement mediated lysis of surface grafted red blood cells. Biomaterials. 2012 Nov;33(31):7871-83.
- Le Y, Li L, Wang D, Scott MD. Immunocamouflage of latex surfaces by grafted methoxypoly(ethylene glycol) (mPEG): proteomic analysis of plasma protein adsorption. Sci China Life Sci. 2012 Mar;55(3):191-201.
- Wang D, Toyofuku WM, Scott MD. The potential utility of methoxypoly(ethylene glycol)-mediated prevention of rhesus blood group antigen RhD recognition in transfusion medicine. Biomaterials. 2012 Apr;33(10):3002-12.
- Chapanian R, Constantinescu I, Brooks DE, Scott MD, Kizhakkedathu JN. In vivo circulation, clearance, and biodistribution of polyglycerol grafted functional red blood cells. Biomaterials. 2012 Apr;33(10):3047-57.
- Wang D, Toyofuku WM, Chen AM, Scott MD. Induction of immunotolerance via mPEG grafting to allogeneic leukocytes. Biomaterials. 2011 Dec;32(35):9494-503.
- Wang D, Kyluik DL, Murad KL, Toyofuku WM, Scott MD. Polymer-mediated immunocamouflage of red blood cells: effects of polymer size on antigenic and immunogenic recognition of allogeneic donor blood cells. Sci China Life Sci. 2011 Jul;54(7):589-98.
- Greco CA, Maurer-Spurej E, Scott MD, Kalab M, Nakane N, Ramírez-Arcos SM. PEGylation prevents bacteria-induced platelet activation and biofilm formation in platelet concentrates. Vox Sang. 2011 Apr;100(3):336-9.
- Le, Y. and Scott, M.D. Immunocamouflage: The Biophysical Basis of Immunoprotection by Grafted Methoxypoly (Ethylene Glycol) [mPEG]. Acta Biomaterialia, 6:2631-2641 (2010).
- Sutton, T.C. and Scott, M.D. The Effect of Methoxypoly(Ethylene Glycol) Chain Length on the Inhibition Of Respiratory Syncytial Virus (RSV) Infection And Proliferation Biomaterials, 31:4223-2230 (2010).
- Rossi, N.A.A., Constantinescu, I., Scott, M.D., Brooks, D.E., Kizhakkedathu, J.N. Enhanced cell surface polymer grafting in concentrated and non-reactive aqueous polymer solutions J. Am. Chem. Soc., 132:3423-3430 (2010).
- Rossi, N.A.A., Constantinescu, I., Kainthan, R.K., Brooks, D.E., Scott, M.D.; Kizhakkedathu, J.N. Red blood cell membrane grafting of multi-functional hyperbranched polyglycerols. Biomaterials, 31:4167-4178 (2010).