Dr. Andrea Clark

Assistant Professor
Email: 
alclark@uoguelph.ca
Phone number: 
ext. 52134 (Office)
Office: 
ANNU 350
Lab: 
ANNU 307

My interest in cartilage and osteoarthritis began during my Ph.D. with Dr. Walter Herzog at the University of Calgary. From the first time I looked down a microscope and saw the cartilage cells (chondrocytes) and the way they were shaped and positioned within the cartilage matrix I was hooked. I thought the complex structure/function relationship between the various cartilage components and the health and viability of the tissue was brilliant, and was motivated by the opportunity to make a contribution to knowledge of osteoarthritis and thus serve those suffering from this painful and debilitating disease.

My Ph.D. focused on the cartilages of the patellofemoral joint, a compartment of the knee often ignored in studies of osteoarthritis. I found that the juxtaposed cartilages and chondrocytes of the patellofemoral joint were heterogeneous mechanically, histologically, biologically and in their response to anterior cruciate ligament deficiency and an applied load.

For my post-doctoral, training I moved south of the border to Duke University, NC. Under the supervision of Dr. Farshid Guilak I was trained in confocal microscopy - a combination of lasers and microscopy that enable the visualization of live chondrocytes in their native tissue environment in real time - and studied the role of the ion channel transient receptor potential vanilloid 4 (TRPV4) in chondrocyte transduction of osmotic stress, and in the development of osteoarthritis. I found that the genetic absence of TRPV4 leads to premature and severe osteoarthritis which is exacerbated in males compared to females, and developed and applied a novel confocal microscopy technique to show that TRPV4 is critical for chondrocyte calcium transient response to hypotonicty ex vivo.

As an independent investigator at the University of Calgary and now at the University of Guelph, I continue to utilize genetic and surgical models of osteoarthritis and confocal microscopy techniques to study chondrocytes, cartilage and osteoarthritis.

B.Sc. - Sports Science and Physics, Loughborough University, UK
Ph.D. - Medical Science, University of Calgary, AB
Post-Doctorate - Biomedical Science, Duke University, NC, USA
 

More than 4 million Canadians have arthritis and the number of people living with arthritis continues to increase year after year. Arthritis is responsible for 6% of hospital admissions in Canada and costs Canadians over $6 billion/year in health care expenses and lost work days. Osteoarthritis can involve multiple tissues in a joint and often results in cartilage and meniscal damage, bone sclerosis and synovial inflammation. Current treatments, such as anti-inflammatory drugs, intraarticular steroid injections and joint replacement surgery, alleviate the symptoms (pain, compromised joint function) of osteoarthritis, but do not diminish its signs. A pressing need remains for joint localized therapies and interventions that could slow or ideally stop this debilitating disease.

The long-term objectives of my research program are to:

  1. identify and characterize signal transduction mechanisms through which chondrocytes detect and respond to mechanical and chemical changes in cartilage.
  2. advance our understanding of the molecular underpinnings of osteoarthritis.

In our research, we use genetic and surgical models of spontaneous osteoarthritis (with old age) and post-traumatic osteoarthritis (following injury). We harness confocal microscopy, histology, immunohistochemistry, reverse transcription polymerase chain reaction and micro-computed tomography technologies to follow the progression of osteoarthritis in a joint and to bring to light the mechanisms by which proteins such as TRPV4, integrin α1β1 and cilia can influence chondrocyte signal transduction and thus the development of osteoarthritis. Through our studies of chondrocyte signal transduction and osteoarthritis we hope to identify novel approaches for improved treatments of this disease that will relieve the suffering of Canadians living with osteoarthritis.

*Shin SY, Pozzi A, Boyd SK and Clark AL: (2016) Integrin α1β1 protects against signs of post-traumatic osteoarthritis in the female murine knee partially via regulation of epidermal growth factor receptor signaling. Osteoarthritis and Cartilage 24:10:1795-1806.

Mickiewicz B, *Shin SY, Pozzi A, Vogel HJ and Clark AL: (2016) Serum metabolite profiles are altered by erlotinib treatment and the integrin α1-null genotype, but not by post traumatic osteoarthritis. Journal of Proteome Research 15:3:815-825.

*Jablonski CL, *Ferguson S, Pozzi A and Clark AL: (2014) Integrin α1β1 participates in chondrocyte transduction of osmotic stress. Biochemical and Biophysical Research Communications 445:1:184-190.

*Parekh R, *Lorenzo M, *Shin SY, Pozzi A and Clark AL: (2014) Integrin α1β1 differentially regulates cytokine-mediated responses in chondrocytes. Osteoarthritis and Cartilage 22:3:449-508.

*Rich DR and Clark AL: (2012) Chondrocyte primary cilia shorten in response to osmotic challenge and are sites for endocytosis. Osteoarthritis and Cartilage 20:8:923-930.

HHNS*6800 - Research Frontiers in Integrative Biomechanics and Neurophysiology

KIN*1040 - Human Anatomy II


I am always looking for hard working, self-motivated and enthusiastic students who share my interest in chondrocyte signal transduction and osteoarthritis. If you would like to join my team as an undergraduate student (research project class, summer research project, work study student, volunteer), graduate student (MSc (thesis or coursework) or PhD) or postdoctoral fellow, please email me with your CV and transcripts.

 

Current Lab Members:

Jana Michaud (RLAT/RVT) Technician
Valerie Wai MSc
Alicia Black MSc
Sabrina Lee BSc
Lauren Stam BSc
Anastassia Borisenko BSc
Lauren Roberts BSc
Alexandra Stroyev BSc
Adam Hoffman BSc
Syed Hussain BSc
Sienna Cole BSc