Dr. Joan Krepinsky

Dr. Joan Krepinsky

Dr. Joan Krepinsky

I am a clinician-scientist with the Division of Nephrology, McMaster University. My practice involves general nephrology and care of patients with chronic kidney disease and kidney failure receiving hemodialysis.


My lab studies the molecular mechanisms involved in the development and progression of chronic kidney disease secondary to hypertension and diabetes, the most common causes of kidney failure in North America. We primarily study kidney (mesangial) cell signaling in in vitro models of intraglomerular hypertension (mechanical stretch) and diabetes (high glucose), specifically related to pathways important in extracellular matrix production and hence kidney/glomerular scarring. Results are tested in relevant animal models including the 5/6 nephrectomy model of hypertensive chronic kidney disease and type 1 diabetes models.

We currently have the following projects:

  1. Why caveolin-1/caveolae deficiency protects against diabetic nephropathy, as shown in our recent Diabetologia publication (2013). Caveolin-1 deficient mesangial cells have significantly elevated levels of the antifibrotic protein follistatin. We are identifying the molecular mechanisms by which caveolin-1 controls follistatin regulation, and the potential therapeutic efficacy of follistatin in protecting against the development of diabetic nephropathy.
  2. We have identified the metalloprotease ADAM17 as an important mediator of extracellular matrix production by mesangial cells in response to high glucose. Studies are now focused on identifying how ADAM17 expression is upregulated and how this enzyme is activated by high glucose. In vivo studies will determine whether ADAM17 inhibition protects against diabetic nephropathy.
  3. We showed that the transcription factor SREBP-1, best known for its role in lipid metabolism, is important to profibrotic signaling by high glucose and TGFβ. Current work is dissecting the molecular mechanism whereby SREBP-1 is activated, how SREBP-1 activation leads to matrix upregulation and whether blockade of its signaling can prevent the development of diabetic nephropathy.
  4. In hypertensive rodents with chronic kidney disease, we showed that Pak1 is activated and upregulated in glomeruli. We also showed that Pak1 is important to matrix upregulation by mechanical stretch. Studies are now underway to determine how Pak1 regulates this process, and whether mice with global Pak1 deletion are protected from kidney fibrosis in this model.
  5. In collaboration with Dr. Austin, also at the HCKR, we are studying the role of TDAG51 in medial vascular calcification asssociated with chronic kidney disease. We have shown that TDAG51 deficiency largely protects mice with chronic kidney disease from medial vascular calcification. Current studies are identifying the molecular mechanism by which TDAG51 prevents the osteogenic differentiation of vascular smooth muscle cells. We are also determining how TDAG51 suppresses the expression of the anti-calcification enzyme ENPP1.


I presently receive funding from the Kidney Foundation of Canada and two 5-year CIHR grants.


Via PubMed, http://www.ncbi.nlm.nih.gov/pubmed?term=Krepinsky%20JC