Ana Konvalinka
Administrative Assistant: Sharon Selvanayagam, sharon.selvanayagam@uhn.ca, 416-340-4800 ext. 6950
Research Synopsis
Dr. Konvalinka’s research program is focused on the following three areas:
1. Native and allograft kidney fibrosis represents the final common process of organ failure. Unfortunately, there are currently no effective treatments for kidney fibrosis. The development of novel therapies has been hampered, at least in part, by the lack of early, non-invasive markers of fibrosis. We have identified a group of proteins regulated by a prototypical fibrogenic stimulus, angiotensin II, in kidney cells in vitro and demonstrated that these proteins were involved in kidney fibrosis in vivo. Using mass spectrometry-based assays, we have demonstrated that urine measurements of these proteins reflect kidney allograft fibrosis. We are now examining the ability of our urine fibrosis signature proteins to identify fibrosis early in kidney transplant recipients. We are also studying the mechanisms of regulation of these fibrosis signature proteins. Agents that inhibit these proteins may represent new potential treatments of kidney disease.
2. Antibody-mediated rejection is the leading cause of premature kidney allograft loss. Pathophysiology of antibody-mediated rejection is incompletely understood and therapeutic options are limited. This type of rejection is linked to antibodies directed against the donor allograft, however, not all antibodies lead to allograft injury. What remains unclear is how early kidney antibody-mediated injury in AMR is initiated and perpetuated by the antibodies. We are utilizing systems biology and proteomics approaches to identify compartment-specific proteome changes in antibody-mediated injury and antibodies more likely to cause graft injury. We will also be utilizing single cell analyses of kidney allograft biopsies to understand the interactions between immune and parenchymal cells in the kidney microenvironment. We aim to identify new therapeutic targets of antibody-mediated rejection.
3. Male sex has been associated with increased risk of progression of kidney disease, but the mechanisms underpinning this phenomenon are poorly understood. We have recently discovered that male sex hormones affect metabolic enzymes in kidney cells and may result in maladaptive changes in the kidney. Interestingly, male kidney cells demonstrate alterations in metabolism, compared to female kidney cells and these alterations are further accentuated by male sex hormones. We are now investigating how sex hormones and sex of the cell affect metabolism and whether we can modify the maladaptive changes in male cells through manipulation of metabolism.