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Casimiro Gerarduzzi, PhD

Award: KRESCENT New Investigator Award
Institution: Hôpital Maisonneuve-Rosemont
​Year: 2018-2021

Study title: The role of matricellular proteins in kidney repair and development

Lay Summary
The proper functioning and survival of cells require an accommodating environment, similar to a seed surrounded by fertile soil. This soil, which we call the ExtraCellular Matrix (ECM), surrounds cells (seeds) with the optimal conditions required for cells to thrive and function correctly.

Diabetic patients develop significant damage to the kidney’s ECM structure (composition and texture), which then requires continuous repair using new ECM materials. ECM repair can remain continuously activated in patients with diabetic kidney disease, and although it seems counterintuitive this “turned on” repair is harmful to cells due to a continuous buildup in new ECM material that eventually replaces the cells needed for proper kidney function. By attempting to return a chronically injured kidney back to health this process actually leads to serious and life-threatening complications and eventually death.

The ECM is also very important in kidney cancer. ECM “soil” is markedly different between normal cells and cancerous cells, and researchers have recently discovered that the structure of cancerous ECM (bad soil) evolves to be different from that of a normal kidney (good soil), thereby developing into an optimal environment for the continued growth of cancer cells (bad seeds). Cancerous ECM evolves even further in a way that supports cancer metastasis, allowing cancer cells to spread to other parts of the body. In this context, identifying and inhibiting factors that regulate ECM expression and processing represent an attractive therapeutic avenue to inhibit the growth and metastasis of cancer cells in Renal Cell Carcinoma patients (RCC).

Learning more about the ECM is an exciting opportunity to correct its regulation during excessive and uncontrolled ECM remodeling in life-threatening conditions such as diabetic kidney disease and RCC. Our laboratory has taken the approach of screening large amounts of genes and proteins in RCC and diabetic kidney disease to identify those involved in ECM regulation. We have an excellent team of nephrologists and renal biomedical researchers working together to validate our identified genes/proteins in diabetic kidney disease and RCC patients, and we will then be able to better understand their relevance to diabetic kidney disease and RCC in well-established animal models. Finally, we will use our animal models to test for new therapeutic options that will improve the quality of life of patients with kidney disease.