Current Title and Department: Robert  L. and Mary Ellenburg Professor of Surgery, Professor, Department of Orthopaedic Surgery and Bioengineering

Current Employer: Stanford University

Undergraduate Degree, University: University of Toronto

Graduate Degree, University: University of Toronto and Lund University

Post-doctoral Position: Orthopaedic Clinical and Research Fellow, University of Toronto

Mentors: Dr Joseph Schatzker, Dr. Victor Fornasier

What led you to study the effects of the immune system on bone healing? What was your first project on osteoimmunology?

When I was an orthopaedic resident, I performed a clinical-radiological-pathological study on the mechanisms of failure of resurfacing arthroplasty of the hip with Dr Joseph Schatzker and Dr. Victor Fornasier. This study, published in the Journal of Bone and Joint Surgery, highlighted the importance of the foreign body and chronic inflammatory response to byproducts of implants for joint replacement. Many other studies followed, using tissue retrievals and in vitro and in vivo models. Inflammatory processes, the immune system, and tissue engineering and repair are a closely linked phenomenon, so studying the relationship between the immune system and bone healing was a natural development for scientific exploration.

What has been your most unexpected result when studying the immune response in bone healing?

We knew that T lymphocytes (memory T cells) and macrophages (trained immunity) have memory, i.e. they respond to stimuli based on their previous exposure to the same or similar stimuli. In our lab, Dennis Lin showed for the first time that Mesenchymal Stem Cells (MSCs) have not only immunomodulatory properties, but they also have memory (Lin et al.  FASEB J. 2019 Mar;33(3):4203-4211. PMID: 30521384).  This study has important implications for immunomodulation, healing of bone, and other mesenchymal derived tissues exposed to injurious environments.

 What is/are your current interest(s) in the field of osteoimmunology?

Our laboratory is focused on the interactions and crosstalk among cells of the immune system, mesenchymal and vascular lineages to facilitate musculoskeletal tissue healing. Interestingly, these biological relationships have broad applicability to those in other organ systems.

What advantages and challenges are associated with studying osteoimmunology in your research model?

We attempt to look at biological events using numerous methods and techniques using tissue retrievals, and in vitro and in vivo models to cross-validate our concepts and hypotheses. We also combine more standard imaging, histological, cell and molecular biological techniques with the newer single cell techniques including mass cytometry, RNA sequencing, etc. Having great collaborators who perform cutting edge research is a huge asset.  Research fellows and post-doctoral students seem to teach me more than I teach them! Having clinical translational perspective and a good mix of experienced people in the laboratory are important.

The major challenge for all of us is to maintain continuous funding to keep the research momentum. One project leads to another idea very quickly. The ability to respond to new scientific questions and findings expeditiously is the key, or quickly you become “the second man to walk on the moon”!

Is there a specific barrier that once addressed might expand clinical translation of osteoimmunology research?

Cell therapy and newer biological therapies are still in their infancy. These treatments are currently used mostly for cancer and severe debilitating diseases. Once we understand more about the interactions of the immune system and the musculoskeletal system, perhaps we can expand our cutting-edge therapies to other scenarios such as the treatment of nonunions, severe bone loss, osteoporosis, etc. However, interventions must be shown to be safe and effective but potential treatments must also be cost-effective. Translation from bench to beside is a very expensive and tedious task.

What advice would you give investigators who want to include osteoimmunology into their research program? What learning resources or techniques would you recommend?

This area is very wide open. Have sound evidence-based hypotheses and garner the necessary resources and infrastructure to test your hypotheses. Take chances; don’t be afraid to fail….we all have!

Find collaborators who can help you in your research; no one can do it all by themselves today. Stay on top of the latest advancements and techniques in your field; they change quickly. Go to meetings and present your research. Others will begin to recognize your expertise and will want to collaborate.

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