Academic Rank:
Clinical Professor
Associate Director, Intellectual Property Senior Scientist
Affiliation(s):
Centre for Blood Research
Location:
Centre for Blood Research, Life Sciences Centre

Short Bio:

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 inactivasion 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.

Academic Backgrounds:
  • PhD, University of Minnesota, Pathobiology (pathology and Laboratory Medicine). 1988
  • MA, Western State College, Gunnison, CO, Science. 1984
  • BA, Western State College, Gunnison, CO, Biology / Psychology. 1979
Selected Publications
  • Chapanian R, Constantinescu I, Medvedev N, Scott MD, Brooks DE, Kizhakkedathu JN. Therapeutic cells via functional modification: influence of molecular properties of polymer grafts on in vivo circulation, clearance, immunogenicity, and antigen protection. Biomacromolecules. 2013 Jun 10;14(6):2052-62.
  • Kwan JM, Guo Q, Kyluik-Price DL, Ma H, Scott MD. Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells. Am J Hematol. 2013 Aug;88(8):682-9.
  • 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.
  • Rossi NA, Constantinescu I, Kainthan RK, Brooks DE, Scott MD, Kizhakkedathu JN. Red blood cell membrane grafting of multi-functional hyperbranched polyglycerols. Biomaterials. 2010 May;31(14):4167-78.
  • Rossi NA, Constantinescu I, Brooks DE, Scott MD, Kizhakkedathu JN. Enhanced cell surface polymer grafting in concentrated and nonreactive aqueous polymer solutions. J Am Chem Soc. 2010 Mar 17;132(10):3423-30.
  • Sutton TC, Scott MD. The effect of grafted methoxypoly(ethylene glycol) chain length on the inhibition of respiratory syncytial virus (RSV) infection and proliferation. Biomaterials. 2010 May;31(14):4223-30.
  • Le Y, Scott MD. Immunocamouflage: the biophysical basis of immunoprotection by grafted methoxypoly(ethylene glycol) (mPEG). Acta Biomater. 2010 Jul;6(7):2631-41.
Research:
  • Hematology and Immunology
  • Immunocamouflage of Blood Cells – Red Blood Cells, Leukocytes, and Platelets
  • Redox-Mediated Erythrocyte Injury
  • Anti-Viral Prophylaxis
  • Iron Chelators

 

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 mediated by a self-propagating, self-amplifying redox reaction initiated by the initial autoxidation of the sickle hemoglobin or unpaired alpha and beta hemoglobin chains. Subsequent glutathione-driven, iron-mediated, 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.