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Ariel Feldstein, M.D.Staff
Department of Cell Biology |
Area of general research interest:
- The liver in obesity and type 2 diabetes
- Mechanisms of lipotoxicity
- Mechanisms of inflammation and fibrogenesis during chronic liver injury
- Lipid homeostasis and liver carcinogenesis
Current program:
- Characterizing the lysosomal – mitochondrial crosstalk in in-vitro cell models and in-vivo murine models of steatohepatitis
- Characterizing mechanisms that initiate mitochondrial reactive oxygen production in models of nonalcoholic and alcoholic steatohepatitis
- Defining the mechanisms responsible for disease progression and fibrogenesis in steatohepatitis by using genetically altered mouse
- Characterizing the links between lipid metabolism, tumor survival and resistance to chemotherapy
- Identifying novel biomarkers for noninvasive diagnosis of steatohepatitis and liver fibrosis
Investigators:
- Tamali Bhattacharyya,M.D, Fellow
- Samiksha Bansal, M.D, Fellow
- Michael Berk, Lead Technologist
- ZhengZheng Li, M.D., Senior Technologist
Collaborators:
- Gregory Gores,M.D., Department of Gastroenterology and Physiology, Mayo Clinic College of Medicine
- Stanley L. Hazen, M.D., Ph.D. Department of Cell Biology, Cleveland Clinic
- Thomas McIntyre, Ph.D. Department of Cell Biology, Cleveland Clinic
- Philip Schauer, MD. Department of Surgery, Cleveland Clinic
- Laura Nagy, Ph.D. Department of Pathobiology, Cleveland Clinic
- Lisa Yerian, M.D. Department of Pathology, Cleveland Clinic
- Xiao-Ming Yin, Ph.D. University of Pittsburgh
- Mina Woo, M.D. University of Toronto
Brief description:
Laboratory-based research: My laboratory-based program is focused on dissecting the intracellular pathways that trigger apoptosis by overaccumulation of lipids in nonadipose cells, which may play an important role in disease processes such as obesity-associated liver disease (nonalcoholic fatty liver disease or NAFLD), and type 2 diabetes.
A second objective is to better understand the events that link excessive accumulation of lipids in the liver (steatosis) to liver injury, scarring and carcinogenesis.
Clinical research: I develop and participate in clinical research protocols in pediatric and adult liver diseases. A current focus is on the development of novel biomarkers for non-alcoholic steatohepatitis (NASH) diagnosis.
We also participate in unique single- and multi-institution treatment protocols for this disease (the NIH’s Clinical Research Network in Non-Alcoholic Steatohepatitis).
Key References:
- Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 2007;46:582-9.
- Wieckowska A, et al. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006;44:27-33.
- Feldstein AE, et al. Bax inhibition protects against free fatty acid-induced lysosomal permeabilization. Am J Physiol Gastrointest Liver Physiol 2006;290:G1339-46.