Meet the Researcher: Mark Scott

By Fennie Easton van der Graaf, Undergraduate Student, Jefferies Lab, CBR

Originally posted on the Canadian Blood Services RED blog on March 28, 2018: https://blood.ca/en/blog/2018-03/meet-researcher-dr-mark-scott

For the latest edition of “Meet the researcher”, Fennie Easton van der Graaf, an undergraduate researcher at the University of British Columbia, chatted with Dr. Mark Scott, Canadian Blood Services’ senior scientist and a pioneer in immunocamouflage of cells to prevent their detection by the immune system.

How long have you been with Canadian Blood Services?
I have been with Canadian Blood Services since 2002.

What’s your role? Mark Scott I am a senior scientist in the Centre for Innovation. From 2006-2013, I was also the associate director for intellectual property and business development at Canadian Blood Services. At the University of British Columbia (UBC), I am a clinical professor within the department of pathology and laboratory medicine and the Centre for Blood Research.

Where is your lab? 
My lab is located in the Centre for Blood Research on the 4th floor of the Life Sciences Centre at UBC. Our team is a very friendly, hardworking group, and as a family we share expertise to support individual projects, which connect together to further our overarching lab goals. We frequently collaborate with other UBC lab groups and generate joint publications.

Tell us more about your scientific background?
I have benefitted from a very diverse scientific background that started with a PhD in pathobiology (studying bacteria) from the University of Minnesota, and a postdoctoral position in hematology in California. In the Children’s Hospital Oakland Research Institute, I studied iron-mediated damage to red blood cells (RBC) in sickle cell disease, thalassemia, and malaria.  As an associate professor at Albany Medical College in New York, my research transitioned from how RBCs are damaged in disease to blood transfusion compatibility.

My lab discovered that we could chemically glue biologically safe polymers to the surface of donor RBCs. When we use the polymer PEG, this process is called “PEGylation”. PEGylation of RBCs prevents the recipient (or “host”) immune system from recognizing donor cells. This can prevent unwelcome immune responses that occur when the donor and recipient are not compatible, which lead to rejection of the RBCs and illness in the recipient. We also call these PEGylated RBCs “stealth RBCs”, and we call the process of PEGylated “immunocamouflage”, as it allows RBCs to avoid detection by the immune system. The development of stealth RBCs caught the attention of Canadian Blood Services. Throughout my journey in Canadian Blood Services, I have had the opportunity to evolve my research on stealth RBCs to further design a unique, broadly applicable, bioengineering approach that directly addresses the issues of tissue transplant rejection and autoimmune disease.

Mark Scott

Dr. Scott early in his career in a lab in Paris

What are your main areas of research and how have they developed?
The major focus of our research is the use of polymer-based bioengineering to modulate the immune system. As described above, one long standing interest is to modify RBCs to prevent or treat transfusion rejection. We are also using this polymer-based approach to redirect the immune system into a more tolerant state in patients who receive tissue transplants or have chronic autoimmune diseases.

This focus was really kick-started by our research on stealth RBCs. Our studies showed that the PEGylated RBCs were not recognized by host antibodies, and so the donor blood was not rejected. The polymer acts as a physical barrier: PEG resembles cooked strands of spaghetti and so the polymer creates spaces, which cause the loss of interaction and communication between host immune cells and donor cells. The polymer also masks the surface charge on the RBC. As a result, instead of attacking the donor cells, the immune system ignores them.

In pursuing this PEGylation technology in white blood cells, we ultimately discovered that we didn’t actually need to use these modified cells to have an effect. We found that if we purified certain components from outside the cells – small molecules called microRNA (miRNA) – we could induce the same effect. We can produce a cocktail of miRNAs that modulate the immune response of animals to induce either tolerance (a low immune response) or inflammation (a high immune response).

We brought these observations from the petri dish into diabetic mouse models, and found that our miRNA therapeutic significantly decreased the risk of type 1 diabetes – an autoimmune disease. This miRNA-based product (called TA1) had redirected the immune system, making it more tolerant. Conversely, we have generated another miRNA-based product (called IA1) that can induce an enhanced pro-inflammatory response. This could help boost the immune response in individuals that are immunocompromised, are battling cancer, or are experiencing pathogenic infections as a consequence of immunosuppression after transplantation.

What are you working on right now?
We are continuing to pursue the use of stealth RBC in transfusion medicine as well as our cellular and miRNA-based immunomodulation therapies. In addition, in collaboration with Dr. Hongshen Ma at UBC, we are investigating microfluidic technologies to measure the effects of RBC storage (up to 42 days) on RBC deformability; a critical feature necessary for RBC survival in the blood stream. From this, the biological quality of stored RBCs could be assessed, reducing risks associated with blood transfusions.

We have also been investigating the challenges related to our polymer bioengineering technique; we hope to produce clinically effective TA1 and IA1 products that have the potential to be brought to the pharmaceutical market.

What other areas of research are you interested in?
I am also interested in the use of polymers on or against viruses. Our initial research in this area began with the idea that we could use PEGylation of adenoviruses to improve gene therapy.  A problem with viruses as gene carriers was that the immune system would kill the ‘helpful’ virus preventing expression of the useful gene. We were unable to simultaneously immunocamouflage the virus as well as permit the virus to infect the cell, but naturally there was a flip side to this dilemma – we could prevent viral infections. This finding reoriented our approach to ask the more interesting scientific question: could we make a polymer-based antiviral gel?

This question is my current pet project. The polymer gel can be applied intra-nasally to almost immediately prevent respiratory infections. I like to refer to this as “Dr. Mark’s Nose Juice” or as ‘Scott’s Snot Preventer”, and we have shown that a single application (apply, massage, blow your nose) is effective for at least 48 hours. This technique also utilizes polymer bioengineering technology such that the virus is unable to recognize and bind to host nasal cells. This is ideal for refugees in post-natural disaster containment areas, or patients in overcrowded hospitals, as respiratory diseases are frequently their first visitor.

What work are you most proud of? 
I am most proud of the polymer bioengineering research because of its broad applicability and potentially practical utility in a broad range of clinical situations ranging from transfusion and transplantation medicine, to autoimmune diseases, cancer and even the prevention of the common cold.  We truly believe that this bioengineering technique can be effectively administered to save lives. Our findings could generate the opportunity for Canadian Blood Services to better use donor blood collections, especially white blood cells that are generally thrown away during blood donation.

With the support of Canadian Blood Services, the main philosophy of my lab has been to generate usable products which can either evade (e.g., stealth RBC) or retrain the immune system of the recipient. As a result of this approach, we have more than 20 pending and issued patents. We hope that these approaches will provide a more cost-effective alternative to commonly administered immunosuppressant drugs.

Mark Scott

Dr. Scott with the Peace Corps in Niger, 1980

What inspired you to pursue science?
My experience with the United States Peace Corps in Niger was very influential in driving me towards studying disease pathology. As a rodent control biologist, I became acutely aware of the local healthcare practices and this instilled my motivation towards pursuing medical research. With limited resources and limited medical expertise, there were many villagers suffering from polio, leprosy, and other diseases. But life could be fun too. In the village I lived in (Dakoro), I had one of the very few kerosene powered refrigerators and every summer, when the heat was impenetrable, that children would line up outside my house to receive ice cubes from my refrigerator (nothing is better than an ice cube when it is 45°C). Although I really appreciated the villagers’ way of life, I came back from my trip inspired to pursue healthcare-related research.

What do you find most exciting about your work? 
My research is highly interdisciplinary encompassing hematology, immunology, virology, and redox biology, and I have connected these disciplines through polymer bioengineering. Our research demonstrates how widely applicable the PEGylation technology can be with applications in transfusion and transplantation medicine, treatment of autoimmune diseases, cancer and even the prevention of the common cold.

When you’re not in the lab where could we find you?
You’ll find me outdoors with my wife, walking and scent training our German Shepherd, Link.  In addition, I enjoy gardening, reading mystery novels or a newly discover love, 3D printing!

Where can I find more information about your research?
To learn more, check out my Canadian Blood Services profile or my lab website.

 

To learn more about Dr. Scott’s immunocamouflage research, check out this R.E.D. blog post. Learn how Dr. Scott’s research could provide hard-to-match patients with safe blood products for transfusions and has the potential to make tissue transplantation safer and more accessible.

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