Important Findings of the Francis Lab
Heather Francis, PhD, and her research team have specifically identified important findings that may lead to early diagnosis and potential therapies for liver disease.
Mast Cell Discoveries
In both rodent and human models, the Francis lab has found that mast cells play a critical role in not only the initial repair of the liver, but also in the progression of liver damage and disease.
Mast cells migrate in close proximity to damaged bile ducts during PSC and CCA and release inflammatory mediators like histamine. Blocking both mast cell migration and the release of mast cell-derived histamine using an FDA approved drug, cromolyn sodium, improves hepatic damage and fibrosis in both human and rodent models of PSC and CCA.
The Francis lab has developed a novel technique to isolate mature hepatic mast cells from rats. Bile acids like ursodeoxycholate (UDCA) can inhibit mast cell release of histamine and improve liver function and ameliorate damage and fibrosis in PSC mice.
Complete loss of mast cells using mast cell deficient mice reveals that, when subjected to injury, the lack of mast cells decreases the degree of damage and fibrosis seen in typical cholangiopathies.
By using over-the-counter drugs that block H1 and H2 histamine receptors, the Francis lab has been able to decrease biliary damage and hepatic fibrosis via the loss of mast cell function in these models.
Histamine Synthesis Discoveries
In mice lacking histidine decarboxylase (HDC, the enzyme that promotes histamine synthesis) fed a high fat, high sugar water diet there is increased weight gain and fatty liver damage, but decreased fibrosis and biliary damage. Further, the histamine-leptin signaling pathway is disrupted in these mice fed high fat, high sugar water diets, which is a potential area that could be targeted in non-alcoholic fatty liver disease.
Loss of histidine decarboxylase (HDC) impairs proper liver regeneration following 70% partial hepatectomy.