Contact Information
UBC Life Sciences Centre
#4464 – 2350 Health Sciences Mall
Vancouver, British Columbia
Canada V6T 1Z3
Tel: 1-604-822-4976
Email: mdscott@mail.ubc.ca
Current Positions
- Clinical Professor, Pathology and Laboratory Medicine.
- Senior Scientist, Centre for Innovation, Canadian Blood Services.
- Associate Director for Intellectual Property and Business Development, Canadian Blood Services.
Research Interests
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.
Publications
- Kang, N., Guo, Q., Islamzada, E., Ma, H., and Scott, M.D., Microfluidic determination of lymphocyte vascular deformability: Effects of intracellular complexity and early immune activation. Integrative Biology, 10:207-217 (2018).
- Matthews, K., Duffy, S.P., Myrand-Lapierre, M.-E., Ang, R.R., Li, L., Scott, M.D., and Ma, H. Microfluidic analysis of red blood cell deformability as a means to assess hemin-induced oxidative stress resulting from Plasmodium falciparum intraerythrocytic parasitism. Integrative Biology, 9(6):519-528 (2017).
- Kang, N., Toyofuku, W.M., Yang, X. andScott, M.D.Inhibition of Allogeneic Cytotoxic T Cell (CD8+) Proliferation Via Polymer-Induced Treg (CD4+) Cells. Acta Biomaterialia, 57:146–155 (2017).
- Scott, M.D., Toyofuku, W.M., Yang, X., Raj, M. and Kang, N. Chapter X: Immunocamouflaged Red Blood Cells: Polymer-Based Bioengineering of Allogeneic Erythrocytes for Use in Alloimmunized Patients. In: Transfusion Medicine and Scientific Developments (Editor: Koopman-van Gemert, A.), INTECH Book, in press. ISBN 978-953-51-3320-9 (2017).
- Le, Y., Toyofuku, W.M. and Scott, M.D. Immunogenicity of Murine mPEG-Red Blood Cells and the Risk of Anti-PEG Antibodies in Human Blood Donors. Experimental Hematology 47(3):36-47 (2017).
- Kyluik-Price D.L., Li, L. and Scott, M.D. Effects of Methoxypoly (Ethylene Glycol) Mediated Immunocamouflage on Leukocyte Surface Marker Detection, Cell Conjugation, Activation and Alloproliferation. Biomaterials 74(1):167-177 (2016).
- Wang, D., Shanina , I., Toyofuku, W.M., Horwitz, M.S. and Scott, M.D. Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy. PLoS ONE 10(12): e0145179. doi:10.1371/journal. pone.0145179 (2015).
- Li, L., Noumsi, G.T., Kwok, Y.Y.E., Moulds, J.M. and Scott, M.D. Inhibition of Phagocytic Recognition of Anti-D Opsonized Rh D+ RBC By Polymer-Mediated Immunocamouflage. American Journal of Hematology, 90(12):1165-1170 (2015).
- Matthews, K., Myrand-Lapierre, M.-E., Ang, R.R., Duffy, S.P., Scott, M.D., and Ma, H.Microfluidic Deformability Analysis of the Red Cell Storage Lesion. Journal of Biomechanics, 48(15):4065-4072 (2015).
- Guo, Q., Duffy, S.P., Matthews, K., Santoso, A.T., Scott, M.D. and Ma, H. Microfluidic Analysis of Red Blood Cell Deformability. Journal of Biomechanics, 47:1767–1776 (2014).
- Kyluik-Price D.L., Li, L. and Scott, M.D. Comparative Efficacy of Blood Cell Immunocamouflage by Membrane Grafting of Methoxypoly(Ethylene Glycol) and Polyethyloxazoline. Biomaterials 35(1):412-422 (2014).
- Chapanian, R., Constantinescu, I., Medvedev, N., Scott, M.D., Brooks, D.E., Kizhakkedathu, J. Therapeutic Cells via Functional Modification: Influence of molecular properties of polymer grafts on in vivo circulation, clearance, immunogenicity and antigen protection. Biomacromolecules, 14(6):2052-62 (2013).
- Kwan, J.M., Guo, Q., Kyluik-Price D.L., Ma, H. and Scott, M.D. Microfluidic Analysis of Cellular Deformability of Normal and Oxidatively-Damaged Red Blood Cells. American Journal of Hematology, 88:682–689 (2013).
- Chapanian, R., Constantinescu, I., Brooks, D.E., Scott, M.D., Kizhakkedathu, J. Antigens Protected Functional Red Blood Cells By The Membrane Grafting Of Compact Hyperbranched Polyglycerols. Journal of Visual Experiments, 71:e50075, DOI: 10.3791/50075 (Jan 2, 2013). http://www.jove.com/video/50075/.
Education
- Ph.D., Pathology and Laboratory Medicine, University of Minnesota, USA, 1988.
- Master of Arts in Science, Western State Colorado University, Gunnison, Colorado, USA.
- Bachelor of Arts in Biology and Psychology, Western State Colorado University, Gunnison, Colorado, USA.