Chuhan Chung MD

Associate Professor of Medicine (Digestive Diseases)

Research Interests

Fatty Liver Disease; Hepatocellular Carcinoma; Angiogenic inhibitors; Pigment Epithelium-Derived Factor (PEDF); Thrombospondin-1

Current Projects

1) Lipid regulation in PEDF null animals.

2) Measurement of serum PEDF in obese patients with insulin sensitivity.

3) The role of matrix metalloproteinases in PEDF regulation.

4) Delivery of PEDF in an in vivo model of hepatocellular carcinoma.

5) Measurement of serum angiogenic factors in patients with chronic Hepatitis C virus infection.

Research Summary

Obesity is a risk factor for diseases such as diabetes and the development of cancer. We are studying the role of angiogenesis in these processes. Angiogenesis is usually quiescent in the adult human but becomes disturbed in disease conditions. In diseases characterized by fat accumulation, the endogenous levels of angiogenic inhibitors are decreased or lost. We are evaluating the loss of these endogenous inhibitors of angiogenesis in animal models and measuring their levels in the serum of patients with metabolic diseases.

Extensive Research Description

My academic interest focuses on the role of angiogenic factors in metabolic disorders. Clinically, the rise in obesity in the US increases the risk of developing diseases such as the metabolic syndrome and various gastrointestinal malignancies. Several areas of research are being pursued in relation to these findings.

First, the function of endogenous inhibitors of angiogenesis is being evaluated in animal models with genetic deletion of specific angiogenic inhibitors. Loss of several angiogenic inhibitors such as pigment epithelium-derived factor (PEDF) is associated with ectopic lipid accumulation in animals. Our studies suggest that endogenous inhibitors of angiogenesis serve an important homeostatic function in lipid metabolism.

Second, in collaboration with members of the Sections of Endocrinology and Digestive Diseases, we are evaluating serum angiogenic profiles in patients with metabolic dysfunction. This data may determine whether a serum 'angiogenic score' correlates with different features of metabolism including obesity, insulin resistance and others.

Finally, we have collaborated with the Department of Biomedical Engineering to create PEDF-containing microspheres that can release protein over several weeks. These have been used in animal studies to determine whether PEDF delivery can inhibit tumor growth in vivo.

Selected Publications

  • Chung C, Mader CC, Schmitz J, Atladottir J, Fitchev P, Cornwell M, Koleske AJ, Crawford S, Gorelick FS. The vacuolar-ATPase (V-ATPase) modulates matrix metalloproteinase (MMP) isoforms in human pancreatic cancer. Laboratory Investigation, In Press.
  • Chung C, Shugrue C, Nagar A, Doll JA, Cornwell M, Gattu A, Kolodecik T, Pandol SJ, Gorelick FS. Ethanol Exposure Depletes Hepatic Pigment Epithelium-Derived Factor, a Novel Lipid Regulator. Gastroenterology 2009;136:331-340.
  • Chung C, Doll J, Gattu A, Shugrue C, Cornwell M, Fitchev P, Crawford SE. PEDF Regulates Hepatocyte Triglyceride Content Through Adipose Triglyceride Lipase (ATGL). Journal of Hepatology 2008; 48:471-8.
  • Chung C, Doll JA, Stellmach VM, Gonzales J,Surapureddi S, Cornwell M, Reddy JK, Crawford SE. Pigment Epithelium-Derived Factor (PEDF) is an Angiogenesis and Lipid Regulator that Activates Peroxisome Proliferator-Activated Receptora (PPARa). Adv Exp Med Biol 2008;617:591-7.
  • Browne MB, Stellmach V, Cornwell M, Chung C, Lee EJ, Jameson JL, Reynolds M, Superina RA, Abramson LP, Crawford SE. Gene Transfer of Pigment Epithelium-Derived Factor Suppresses Tumor Growth and Angiogenesis in a Hepatoblastoma Xenograft Model. Pediatr Res 2006;60:282-287.
  • Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT. Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure. Gastroenterology 2003; 125: 755-764.
  • Chung C, Gottstein J, Vaquero J, Blei AT. Vasopressin Accelerates the Development of Brain Edema in Rats after Portacaval Anastomosis. J Hepatol 2003; 39:198-204.

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