Mark Scott, PhD

• Immunocamouflage of Blood Cells - Red Blood Cells, Leukocytes, and Platelets
• Redox-Mediated Erythrocyte Injury
• Anti-Viral Prophylaxis
• Iron Chelators

Dr. Scott's laboratory is focused on three primary areas of research: 1) investigation of the potential therapeutic use of "immunocamouflaged" cells/tissues in transfusion medicine; 2) prevention of viral invasion and disease by the immunocamouflage of viruses or the host cell; 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 induction of tolerance by pre-exposure to immunocamouflaged allogeneic cells.

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 focused on the intraerythrocytic chelation and redox-inactivation of the hemoglobin-derived heme and iron present in the sickle and thalassemic RBC. 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 abnormal erythrocytes may improve the "effective" erythropoiesis (i.e., hematocrit) and reduce transfusions in some patients.

Selected Publications:

Scott, M.D., Murad, K.L., Koumpouras, F., Talbot, M., and Eaton, J.W. Chemical camouflage of antigenic determinants: "Stealth" erythrocytes. Proc. Nat. Acad. Sci. USA, 94:7566-7571(1997).

Scott, M.D. Intraerythrocytic iron chelation therapy: An alternative to blood transfusions? Hematology, 6:73-89(2001).

Chen, A.M. and Scott, M.D. Immunocamouflage: Prevention of transfusion-induced graft-versus-host disease via polymer grafting of donor cells. Journal of Biomedical Materials Research, 67A:626-636(2003) .

McCoy, L.L and Scott, M.D. Broad spectrum antiviral prophylaxis: Inhibition of viral infection by polymer grafting with methoxypoly(ethylene glycol). In: Antiviral Drug Discovery for Emerging Diseases and Bioterrorism (Editor Torrence, P.F.) Wiley & Sons, Hoboken, NJ. pp. 379-395.(2005).

Scott, M.D. H2O2 injury in ß thalassemic erythrocytes: Protective role of catalase and the prooxidant effects of GSH. Free Radicals in Biology & Medicine, 40:1264-1272(2006).

Chen, A.M. and Scott, M.D. Immunocamouflage: Comparative analysis of polymer and linker chemistries on the efficacy of immunocamoulfage of murine cells. Artificial Cells, Blood Substitutes. And Biotechnology, 34:305-322(2006).

Bradley, A.J. and Scott, M.D. Immune complex binding by immunocamouflaged [poly(ethylene glycol)] erythrocytes. Am. J. Hematology, 82:970-975(2007).

Rossi, N.A.A., Zou,Y., Scott, M.D. and Kizhakkedathu, J.N. RAFT Synthesis of Acrylic Copolymers Containing Poly(ethylene glycol) and Dioxolane Functional Groups: Toward Well-De?ned Aldehyde Containing Copolymers for Bioconjugation. Macromolecules, 41:5272-5282 (2008).

Rossi NA, Mustafa I, Jackson JK, Burt HM, Horte SA, Scott MD, Kizhakkedathu JN. In vitro chelating, cytotoxicity, and blood compatibility of degradable poly(ethylene glycol)-based macromolecular iron chelators. Biomaterials, 30:638-648 (2009).