Matthew W. Grol
BMSc Honours Specialization in Biochemistry and Cell Biology, University of Western Ontario
Office: Dental Sciences Building, Room 00079
During my undergraduate education, I became interested in the complex mechanisms that regulate cellular signaling and metabolism, which led me to pursue a biochemistry and cell biology specialization. As part of my fourth-year undergraduate thesis, I worked with the late Dr. Suzanne Bernier to identify cell-surface markers of dedifferentiation in cartilage cells (known as chondrocytes) in vitro. My time in the Bernier lab piqued my interest in musculoskeletal biology. This experience ultimately encouraged me to return to Western University to pursue my doctoral degree in the laboratory of Dr. S. Jeffrey Dixon, where I investigated the role of P2 nucleotide receptor signaling in bone biology. Following my Ph.D., I moved to Baylor College of Medicine in Houston, Texas, and joined the laboratory of Dr. Brendan H. Lee as a postdoctoral fellow. During my time at Baylor, my research focused on evaluating gene therapies for Osteoarthritis (OA) and investigating tendon pathologies in preclinical models of connective tissue diseases such as Osteogenesis Imperfecta (OI). After my postdoctoral fellowship, I returned to Western University as an Assistant Professor and joined the Department of Physiology and Pharmacology and the Bone and Joint Institute.
My research has focused on musculoskeletal biology and connective tissue diseases throughout my training, and my lab will continue in this direction. My interest in this area stems from the illnesses I've experienced through my family members, where my grandmother suffered from severe OA and my younger brother had juvenile rheumatoid arthritis. My doctoral training in the Dixon lab provided me with an understanding of musculoskeletal biology and signaling. And my time with Dr. Brendan H. Lee gave me experience developing novel gene therapy strategies to mitigate disease progression in preclinical models of connective tissue disease. The combination of basic and translational biology will continue in my lab as we aim to identify novel strategies to treat OA and other musculoskeletal disorders.
Osteoarthritis (OA) is a degenerative joint disease characterized by loss of articular cartilage, subchondral bone sclerosis, and low-grade inflammation with synovitis. In turn, these changes lead to chronic pain and functional impairments. While often associated with age and joint injury, OA of early onset also occurs with obesity and genetic disorders of connective tissues such as chondrodysplasia. Unfortunately, despite OA's considerable socioeconomic and health impacts in Canada, there are no disease-modifying therapies. Instead, mainstays of treatment are limited to pain reduction, physical therapy, and, in end-stage disease, joint replacement. As such, there is a significant need for therapies that prevent OA progression, provide pain relief, and reverse established disease.
To achieve this goal, my lab focuses on several interrelated projects that employ surgical and genetic mouse models in combination with gene therapy approaches to identify targets and develop strategies to stop and reverse disease progression in OA and other musculoskeletal disorders.
1. Gene therapy strategies post-traumatic and metabolic forms of OA.The lab utilizes surgical approaches to model post-traumatic OA and diet-induced systems to mimic metabolic forms of this disease. In this context, we examine how local gene therapy strategies can modulate pathological processes to slow OA progression and block associated pain and motor impairments.
2. Mechanisms of pain and motor impairment in OA and rare musculoskeletal diseases. Chronic pain and motor impairment are observed in various musculoskeletal diseases, including OI and OA. Work in the lab focuses on understanding how innervation and pain pathways are altered in mouse models of these diseases and whether these pathways can be targeted therapeutically to block pain and motor deficits.
3.Tendon and ligament development and disease. Tendons and ligaments – composed of an extracellular matrix rich in type I collagen – are critical for joint stability and function. Mice with deficiencies in collagen synthesis and processing develop hallmarks of tendinopathy, including hypercellularity, altered collagen fibril size and organization, and reduced biomechanical strength. In this context, the lab examines how disruptions to the tendon and ligament ECM leads to altered matrix-to-cell signaling, and how, in this context, aberrant local inflammation and cellular metabolism leads to premature joint failure.
Most Rewarding Moments:
In terms of scientific landmarks, my Ph.D. research identified a novel dose-to-duration signaling mechanism imparted by the complex networks of P2 nucleotide receptors expressed on bone-forming osteoblasts. This finding may explain how bone senses mechanical signals of differing strength. As for my postdoctoral work, an anti-inflammatory gene therapy I worked on in Dr. Lee’s lab was recently approved for Phase I clinical trials in the U.S.A. for patients with moderate-to-severe OA. This is particularly important for the field as a proof-of-concept for viral gene therapy strategies for OA. In addition to this, we also provided detailed characterization of tendon and ligament phenotypes in a preclinical model of severe, recessive OI.
Advice to Students:
Always follow what the data tells you rather than conform to what you think the result should be. Sometimes the question you pose is interesting, but you end up finding an even more exciting question or even more exciting explanation than what you hypothesized.
Interests Outside of Academia:
I enjoy all forms of music, and can play 6 different instruments including the piano, organ, trumpet, and baritone.
Awards and Recognitions:
2021 – Tier II Canada Research Chair in Musculoskeletal Biology and Health
2019 – Harold M. Frost Young Investigator Award, American Society for Bone and Mineral Research
2018 – Lawrence Award, Rolanette and Berdon Lawrence Bone Disease Program of Texas
See Publications by Matthew W. Grol on PubMed
Grol, M. W., Haelterman, N. A., Lim, J., Munivez, E. M., Archer, M., Hudson, D. M., Tufa, S. F., Keene, D. R., Lei, K., Park, D., Kuzawa, C. D., Ambrose, C. G., Eyre, D., and Lee, B. H. (2021) Tendon and motor phenotypes in the Crtap-/- mouse model of Osteogenesis Imperfecta. Elife. 10, e63488.
Jayaram, P., Liu, C., Dawson, B., Ketkar, S., Patel, S. J., Lee, B. H., and Grol, M. W. (2020) Leukocyte-dependent effects of platelet-rich plasma on cartilage loss and thermal hyperalgesia in a mouse model of post-traumatic osteoarthritis. Osteoarthritis Cartilage. 28(10), 1385-1393.
Stone, A.*, Grol, M. W.*, Ruan, M. Z. C., Dawson, B., Chen, Y., Jiang, M., Song, I., Jayaram, P., Cela, R., Gannon, F., Lee, B. H. (2019) Combinatorial Prg4 and Il-1ra gene therapy protects against hyperalgesia and cartilage degeneration in post-traumatic osteoarthritis. Human Gene Therapy. 30(2), 225-235. (* denotes co-first authorship)