Molecular and cellular function of vitamin K in health and diseases

Our laboratory is studying the role of vitamin K and vitamin K-dependent proteins in normal physiology and in diseases, including diabetes, osteoporosis and cancer. Two projects are currently available for graduate students or postdoctoral fellow.

Project 1

Vitamin K and bone mass. The first project will focus on understanding how bone mass is regulated by vitamin K, the co-factor of gamma-glutamylcarboxylase, an enzyme modifying specific secreted proteins. The project includes biochemical, cellular and molecular biology approaches, and will take advantage of conditional knockout mouse models to study the function of gamma-carboxylation in vivo in bone and ex vivo in osteoblasts cultures. We are also developing proteomics approaches to identify novel gamma-carboxylated proteins implicated in these biological processes. This project is funded by a 5 years CIHR grant (2018-2023). 

Project 2

Vitamin K and liver cancer. Previous studies suggested that vitamin K deficiency might be implicated in the development of hepatocellular carcinoma (HCC or liver cancer). The current project focus on one enzyme called VKORC1L1 which is implicated in the recycling of vitamin K in the liver. Our preliminary results support an important role for VKORC1L1 in preventing HCC in mouse models. The project will investigate the similarities between human HCC and the disease present in our animal model. We will also determine the role of VKORC1L1 and vitamin K in protecting the liver from oxidative stress, with the ultimate objective to develop more targeted treatments for HCC. This project is funded by a 2 years CRS grant (2019-2021).

The lab

Established in 2013, the Ferron lab is currently composed of 1 research associate and 3 PhD students. The team will expend in the upcoming year since we recently obtained additional funding. This is a great opportunity to join a very dynamic team (>25 publications in past 6 years)!

Suggested recent publications

Lacombe, J., Al Rifai, O., […], Ferron, M.* Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and -cell function. Am J Physiol Endocrinol Metab. 2020. Online.

Lacombe, J., Rishavy, M.A., Berkner, K.L., Ferron, M*. VKOR paralog VKORC1L1 supports vitamin K-dependent protein carboxylation in vivo. JCI Insight. 2018, 3(1): e96501. 

Al Rifai, O., Chow, J., Lacombe, J., Julien, C., Faubert, D., Susan-Resiga, D., Essalmani, R., Creemers, J.W., Seidah, N.G., Ferron, M*. Proprotein convertase furin regulates osteocalcin and bone endocrine function. The Journal of Clinical Investigation. 2017, 127(11), 4104-4117. 


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