Brigstock Lab
The Brigstock Lab’s primary focus is on fibrosis, a pathological process in which excessively large amounts of collagenous scar material are deposited between cells of major organs and tissues. This process usually develops over a protracted time period (frequently measured in years) and is most often a response to chronic injury. Fibrosis is a common feature of numerous varied organ diseases in which it causes impairment of cell-cell communication, aberrant tissue remodeling, alterations in blood flow, reduced tissue or organ function, and increases the probability that more severe chronic conditions such as end-stage organ disease or cancer will develop.
Fibrosis is the cause of considerable morbidity and mortality and has been estimated to contribute to 45% of all deaths in the United States, yet there are currently no FDA-approved therapeutics for most forms of fibrosis.
Pathways of fibrosis involve multiple cell types which communicate in an orchestrated fashion via intercellular signaling networks that involve numerous cell-associated, matricellular or soluble signaling molecules.
In recent years, a new mode of cell-cell communication has been identified that involves the delivery of molecular information in extracellular vesicles (EV). This is now considered to be a significant signaling mechanism by which many homeostatic and pathological processes are regulated. Emerging evidence shows that specific populations of EVs are stimulatory for fibrosis or may possess intrinsic or engineered anti-fibrotic properties; these are the main aspects of EV biology that we are investigating.
The Brigstock Lab researches fibrosis of the liver, which is a common feature of alcoholic liver disease, non-alcoholic liver disease, viral hepatitis, liver cirrhosis and cancer. Using in vitro systems to study the involvement of EVs in communication between liver parenchymal cells (e.g. hepatocytes) and non-parenchymal cells (e.g. hepatic stellate cells, macrophages, endothelial cells), the lab’s team aims to identify molecules in EVs that can drive or suppress fibrogenic pathways, or that are important for EV release or that mediate binding between EVs and their target cells. It is also using hepatic fibrosis models in mice to determine the pro-fibrotic or anti-fibrotic actions of specific sub-populations of EVs. The elucidation of fibrogenic mechanisms at the molecular level will likely result in the identification of many rational therapeutic targets, and an improved understanding of EV in fibrosis will likely result in additional therapeutic advances.
