My research area encompasses Metabolic and Tissue Engineering. In the former, we are developing a systems biology framework to characterize and treat the metabolic derangements of disease. Cellular metabolism occurs within a complex network of chemical reactions, is regulated at multiple levels (metabolites, proteins, genes and so on), and therefore therapies require a combination of approaches to simultaneously address multiple targets. To identify these targets, we gather large sets of metabolic data from disease models and combine them with mass balance analysis methods to generate a comprehensive map of the metabolic changes within the major metabolic pathways induced by disease. We also work with collaborators to link these observations to gene expression data to elucidate the underlying mechanisms responsible for the changes. This information provides a rational basis to develop multi-pronged therapies. We apply this framework in the context of two different applications: metabolic abnormalities associated with complex diseases, such as adult-onset diabetes, cancer, trauma, and so on, and metabolic reconditioning of organs that are rejected from the donor pool. In the area of Tissue Engineering, our focus is to develop methods that attract stem cells to a site of injury in order to promote faster wound healing and reduced scarring. It is known that adult stem cells, some of which coming from the bone marrow, naturally have the capacity to home into injured areas of the body where they grow and differentiate to form new tissue. Our goal is to elucidate this mechanism and to develop methods that enhance it using a combination of implantable polymeric scaffolds and stem cell attracting agents. We are specifically interested to use this strategy for improving the healing of skin wounds, in particular deep skin wounds that are susceptible to infection and scarring, as well as non-healing and chronic wounds, such as diabetic ulcers, venous ulcers, and bed sores.
- Faulknor RA, Olekson MA, Nativ NI, Ghodbane M, Gray AJ, Berthiaume F. Mesenchymal stromal cells reverse hypoxia-mediated suppression of alpha-smooth muscle actin expression in human dermal fibroblasts. BiochemBiophys Res Commun 2015; 458(1):8-13.
- Nativ NI, Yarmush G, So A, Barminko J, Maguire TJ, Schloss R, Berthiaume F, Yarmush ML. Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol. Liver Transpl 2014; 20(8):1000-11.
- Nativ NI, Yarmush G, Chen A, Dong D, Henry SD, Guarrera JV, Klein KM, Maguire TJ, Schloss R, Berthiaume F, Yarmush ML. Rat hepatocyte culture model of macrosteatosis: effect of lipid accumulation and defatting on viability and liver-specific function. J Hepatology 2013;59(6):1307-14.
- Orman MA, Ierapetritou MG, Androulakis IP, Berthiaume F. Effect of fasting on the hepatic metabolic response to experimental burn injury. PLoSOne 2013;8(2):e54825.
- Bohr S, Patel SJ, Sarin D, Irimia D, Yarmush ML, Berthiaume F. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model. Wound Repair Regen 2013; 21(1):35-43.
- Nativ NI, Maguire TJ, Yarmush G, Brasaemle DL, Henry SD, Guarrera JV, Berthiaume F, Yarmush ML. Liver defatting: an alternative approach to enable steatotic liver transplantation. Am J Transplant. 2012; 12(12):3176-83.