Liver disease is not one disease but many with both genetic and environmental causes. Since 1974, Montefiore Einstein’s Marion Bessin Liver Research Center has been bringing basic and translational scientists together with clinical hepatologists to advance scientific and clinical knowledge about liver disease causes, prevention, diagnosis, and treatment. The center is part of the department of medicine’s division of hepatology under the leadership of Allan Wolkoff, M.D.
Meet three DOM scientists who just received R01 grants from the National Institutes of Health whose work has the potential to transform the field of liver disease research.
Dr. Billerbeck has always been interested in viral immunology and the question of how a specific tissue environment shapes the host immune response and the outcome of a virus infection. She found the liver particularly fascinating because under healthy conditions, it is in a state of immune tolerance – limiting immune responses to dietary and antimicrobial antigens derived from the gut. A compromised liver immune system contributes to the development of liver disease, including viral hepatitis, non-alcoholic steatohepatitis (NASH), and liver cancer, so gaining new knowledge about the mechanisms underlying liver immune regulation has enormous public health ramifications. This became a natural research focus for her.
Dr. Billerbeck’s R01 grant will support research on the role of functional distinct T cell and natural killer T (NKT) cell subsets during a viral infection in the liver. T cells are essential for protection from hepatic viruses, but they can also contribute to liver disease progression.
Using a new mouse model of a hepatitis C-related rodent virus infection, Dr. Billerbeck and her team will investigate the impact and interplay of functionally distinct T and NKT cell subsets in the liver, it’s role in viral clearance and protective immunity, and its effects on tissue damage during viral hepatitis infection.
Her work has the potential to aid in the development of preventative vaccines for hepatitis C – which affects some 58 million people worldwide – and immunotherapeutic options for progressive liver disease.
Dr. Eliscovich’s work was inspired by her love of seeing how things function on a molecular level and how high-resolution microscopy reveals the unseen within individual cells.
She became interested in liver biology because the liver has a unique architecture that is not well-understood and found inspiration in how hepatocytes that look identical can express different genes dependent on the microenvironment. She has adapted RNA imaging tools to contribute to the understanding of liver biology and failures during liver disease from the single-cell and single-molecule perspective.
R01 Grant Focus
Failures in glucose and lipid metabolism are hallmarks of insulin resistance and type 2 diabetes. In the liver, this manifests as an inability of insulin to suppress glucose output but still to produce fat.
Dr. Eliscovich’s R01 grant, which she shares with Drs. Jeffrey Pessin and Fajun Yang, will support research on the basic mechanisms that control gluconeogenesis and lipogenesis during the feeding and fasting cycle in mouse liver.
Very little is known about how individual liver cells function in the native context of the liver tissue. As part of her grant, Dr. Eliscovich developed a single-molecule Fluorescence in situ Hybridization (smFISH) method that preserves the in vivo metabolic characteristics of the liver and have found novel aspects of the spatial organization of the hepatocytes. This research will be highly significant because this imaging technology will demonstrate what an individual hepatocyte is doing in a format that maintains the morphology of the tissue and could provide the basis for determining which liver cells are dysregulated in diabetes and other metabolic-related diseases.
As a young scientist, Dr. Arias-Perez dreamed about being awarded an R01 grant and her dream not only came true, but it happened the first time she applied. She credits her many mentors and collaborators and the supportive environment at the Liver Research Center under the direction of Dr. Allan Wolkoff.
Dr. Arias-Perez studies a process that regulates proteins within the cell to maintain health; her work focuses on liver related diseases ranging from non-alcoholic steatohepatitis (NASH) to liver cancer. Because of the global obesity epidemic, NASH is the most common liver disease in industrialized countries. It’s a serious liver disease that can progress to advanced fibrosis, cirrhosis, and liver cancer.
Different systems are responsible for the maintenance of quality control and regulation of metabolic pathways in the liver, and its failure has been involved in hepatic pathology. Malfunction of these surveillance protective systems can influence the progression of NASH into a primary liver cancer called hepatocellular carcinoma (HCC).
Dr. Arias-Perez’s R01 grant will support research into the molecular and cellular relationships that drive hepatic pathology, including the role that selective proteolytic systems play in liver damage progression. The R01 grant will also enable Dr. Arias-Perez and her team to test the possible therapeutic value of enhancing the activity of a selective type of autophagy as a novel approach to ameliorate liver disorders and their progression to HCC.
Says Dr. Arias-Perez, “The excitement when you get this type of recognition for your work is the realization that you will be able to start building a successful research program in such a supportive and nurturing environment as the Liver Research Center.”
[Dr. Arias-Perez wishes to thank her mentors and role models at Einstein, including Drs. Allan Wolkoff, Fernando Macian-Juan, Ana Maria Cuervo, Susmita Kaushik, and Rajat Singh.]
Posted on: Friday, June 24, 2022