Cell-to-cell communication is essential for proper organ function. A key component of this crosstalk involves metabolic coupling where cells exchange nutrients. During pathologies such as cancer, infection, and tissue injury, metabolic exchange is disrupted leading to tissue dysfunction. A key goal of our research is to elucidate the mechanisms of metabolic coupling between cells and develop new therapeutics that target these processes to treat cancer and promote tissue regeneration. We use a set of cutting-edge tools, including metabolomics, scRNA-seq, and multiplexed protein imaging to investigate the regulation of metabolism during health and disease.
Identifying Metabolic Drivers of Pathology in Glioblastoma
Glioblastoma is a common and aggressive malignancy of the brain. The prognosis of patients with this tumor type is poor and median survival is approximately 15 months due to its resistance to current treatments. Our research focuses on defining the metabolic heterogeneity within the tumor microenvironment. By uncovering how cells within the brain communicate with the tumor we hope to development new drugs to treat this cancer. We find that brain tumors have enhanced lipid metabolism and that this metabolic program adversely impacts surrounding healthy tissue. We are interested in exploring how these metabolic changes might be harnessed to prevent glioblastoma growth and reoccurrence.
Manipulating Stem Cell Metabolism to Promote Tissue Repair
The repair of tissues after injury requires recruitment and differentiation of stem cell populations. Cell division and differentiation each require activation of a set of unique cell signaling programs. We are examining how metabolism is controlled by these cellular signals, contributing to stem cell function and successful tissue repair. To do this we use in vitro and in vivo models of tissue damage such as the cuprizone model of demyelination. Ultimately identifying biochemical pathways important for stem cell function will allow the development of new regenerative therapies.
Leveraging Systems Biology to Understand Host Pathogen Interactions.
Viruses hijack the metabolism of host cells to support replication of their genomes and the creation of new viral particles. A goal of our research is to define host dependency factors that are critical for viral pathogenesis. We use a combination of genomics, proteomics, and metabolomics to profile alterations in host biochemistry, signaling and inflammatory responses that support viral infection. These host processes are then targeted to develop new antivirals.