BSc, McMaster; PhD, University of Toronto.
The main research focus in the Petkovich lab is understanding the role of hormone receptor signalling in health and disease. Our current efforts are focused on vitamin A and vitamin D signalling and metabolism as they relate to bone development (along with pathological calcification of tissues), skin disorders, kidney disease, and tumour metastasis.
Retinoic acid (RA) is the active metabolite of vitamin A and has several important physiological functions including regulation of cell proliferation and apoptosis, cell differentiation, and tissue morphogenesis. These attributes of RA have been exploited in the clinic for the treatment of skin diseases and make it a strong candidate for cancer prevention and differentiation therapy.
RA distribution is finely controlled by the balanced activities of retinaldhyde dehydrogenases (Raldhs) which control its synthesis and cytochrome P450 enzymes from the CYP26 family which control its degradation. Three CYP26 family members (A1, B1, and C1) were discovered in our lab. Their distribution during embryogenesis clearly indicates that they have distinct roles in defining the distribution of RA in tissues undergoing morphogenesis. We have generated a CYP26 gene-knockout (KO) mouse models, and have analysed their embryonic lethal phenotypes.
These genetic models also allow us to specifically delete Cyp26a1 or b1 in selected tissues. We are currently using these models to assess the impact of altered RA signaling on bone cell differentiation and maintenance. We are also interested in determining whether RA effects on osteoblast differentiation are pertinent to ectopic ossification since diseases such as chronic kidney disease (CKD) can result in inappropriate ectopic phosphatemic activation of osteochondrogenic pathways resulting in mineralization of cardiovascular tissues.
The Petkovich lab is also actively involved in drug development for treatment of diseases that respond to modulators of vitamin A and D signalling, such as CKD, acne, wound healing, and metastasis.