Welcome to the Viswanathan lab

Background - Dr. Viswanathan is a Scientist at the Schroeder Arthritis Institute and the Krembil Research Institute at University Health Network (UHN) and an Associate Professor at the Institute of Biomedical Engineering (BME) and at the Division of Hematology (Department of Medicine) at the University of Toronto. Dr. Viswanathan has worked in industry, developing regenerative medicine products at Johnson and Johnson before returning to academia to run the Cell Therapy Program at University Health Network as Associate Director with Dr. Armand Keating. She enabled over 10 cell therapy trials, both investigator-initiated and industry-sponsored ones during her time at the cell therapy program and garnered a national and international reputation as a translational scientist with cell manufacturing and regulatory expertise. Dr. Viswanathan set up her own independent lab at UHN in 2015.

As a translational scientist, Dr. Viswanathan serves as a national regulatory and cell manufacturing consultant for projects across Canada. Dr. Viswanathan chaired the Cell Therapy Stakeholder Group, a bilateral group that engages Health Canada on cell therapy related policy issues (2015-2020). Dr. Viswanathan is a past member of the Stem Cell Oversight Committee that advises the Governing Council of CIHR. Dr. Viswanathan is a founding member, and team leader of the Manufacturing Committee of a network of Pan-Canadian cell manufacturing facilities called CellCAN. Dr. Viswanathan is leading international efforts to standardize MSC nomenclature and create reference material(s) for MSC research; she sits on the Standard Council of Canada’s Mirror Committee for International Organization for Standardization (ISO TC276) on Analytical Methods and Bioprocessing, and is on the steering and working committee of an international Standards Coordinating Body (SCB), and has recently been appointed as formal liaison between ISO TC276 and the International Society of Cell and Gene Therapy (ISCT). Dr. Viswanathan is Associate Editor of Cytotherapy, official journal for ISCT and has recently been elected to ISCT’s Board of Directors.

Research Interests - My lab’s research interest is focused on developing and cellular therapies, focused primarily on reducing inflammation and modulating the immune system. My lab uses different types of mesenchymal stromal cells (bone marrow, adipose tissue, umbilical cord tissue). I am co-PI of a recently completed trial using autologous bone marrow-derived mesenchymal stromal cells to treat moderate-to-late-stage knee osteoarthritis patients, a Canadian first (NCT02351011 and Chahal et al, 2019, Stem Cells Translational Medicine, ranked #1 most-read paper of 2019 by SCTM).

My lab has developed several methods to enhance mesenchymal stromal cells and are evaluating these for osteoarthritis, diabetic-ulcers and acute respiratory distress syndrome, and other indications.

Bone repair and regeneration using natural and synthetic scaffolds seeded with bone marrow-derived mesenchymal stromal cells are also being pursued in the lab in collaboration with Prof. Eli Sone and Prof. Jon Irish and Harley Chan.

Immunotherapy, primarily focused on developing monocyte/macrophage-based therapies as adoptive transfers are also being developed as novel cellular therapy. This is primarily being tested in the context of osteoarthritis, but is a platform technology for other indications involving monocytes/macrophage dysfunction (Chan and Viswanthan, 2019, Cytotherapy). We are also interested in using small molecules that toggle metabolic pathways (glycolysis vs. oxidative phosphorylation) to drive monocyte/macrophage polarization as part of an adoptive transfer immunotherapy strategy. Some of these small molecules may be used directly to affect endogenous repair.

Understanding the interplay between tissue-resident synovial macrophages (embryonically-derived) and infiltrating bone marrow-derived monocyte/macrophages, and their role in driving OA pathogeneis is key to developing anti-inflammatory and immunomodulatory therapies. We have developed a joint-in-a-dish model with Dr. Rajiv Gandhi to help evaluate cell therapies (and small molecules) with human cells and intact extracellular matrix. We are looking for further develop and refine this model as a screening and evaluation tool.

An underlying focus of my lab is bioprocess optimization. We are systemically evaluating manufacturing parameters that affect MSC yield and potency through a design of experiment approach with Prof. Julie Audet. Combinations of manufacturing parameters are being tested in scalable, vertical-wheel bioreactors to produce clinical quantities of MSCs with intact potency. In parallel, we are exploring closed-system solutions to polarizing monocytes/macrophages and have an industry collaboration with Miltenyi.