Speaker

LALE ÖZCAN

Assistant Professor, Department of Medicine
Columbia University Medical Center

Lale Ozcan received her M.D. degree in 2004 from Istanbul University Cerrahpasa School of Medicine. She then worked in Harvard University from 2004-2008 as a research fellow and the focus of research was to explore the role of Unfolded Protein Response in the regulation of insulin signaling. She joined the laboratory of Dr. Tabas in June 2008 with a great interest in identifying the molecular mechanisms linking Unfolded Protein Response and development of atherosclerosis. She will be mainly focusing on the role of calcium in ER stress-induced apoptosis in macrophages.

Abstract


Individuals with type 2 diabetes (T2D) have a 2–4-fold increase in their lifetime risk of developing cardiovascular diseases, which mostly stems from lipid abnormalities. Therefore identification of druggable molecular targets that contribute to this defect has a tremendous potential to lead to novel treatment modalities. Over the past few years, we have revealed activation of a pathway initiated by calcium-induced activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in hepatocytes which disrupts insulin receptor signaling. Our new data revealed that activation of CaMKII pathway in obesity in turn induces a corepressor called Dachshund homolog 1 (Dach1) which has never before been implicated in metabolism. Dach1 levels are dramatically increased in the livers of obese mice and humans and inhibition of Dach1 in hepatocytes protects against hyperinsulinemia and hyperglycemia. Interestingly, when Dach1 is deleted solely in hepatocytes, there is a significant decrease in plasma cholesterol levels in obese mice independently of its effects on glucose metabolism, which has important implications for obesity/T2D-associated cardiovascular diseases. Thus Dach1-mediated co-repression in hepatocytes might be a critical link between insulin resistance and abnormal lipid metabolism associated with obesity.

Symposium Faculty

ALAN D. ATTIE

Professor, Biochemistry
University of Wisconsin

LAURIE H. GLIMCHER

Professor, Dean of Cornell Medical School

ROBERT FARESE

Professor, Genetics and Complex Diseases
Harvard T.H. Chan School of Public Health

GÖKHAN HOTAMIŞLIGİL

Professor, Genetics and Metabolism and Nutrition
Harvard University

BRIAN KOBILKA

Professor, Department of Molecular and Cellular Physiology
Stanford University

SUSANNE MANDRUP

Professor, Biochemistry and Molecular Biology
University of Southern Denmark

EMILIE MARCUS

CEO of Cell Press and Editor of Cell

RUSLAN MEDZHITOV

David W. Wallace Professor of Immunobiology; Investigator, Howard Hughes Medical Institute, Yale University, HHMI

IRA TABAS

Professor, Anatomy Cell Biology
Columbia University

PETER TONTONOZ

Professor, Pathology and Laboratory Medicine
University of California Los Angeles

DENİZ ATASOY

Assistant Professor, Physiology, School of Medicine
İstanbul Medipol University

EBRU ERBAY

Assistant Professor, Molecular Biology and Genetics
Bilkent University

KIVANÇ BİRSOY

Assistant Professor, Molecular Biology and Genetics
Rockefeller University

LALE OZCAN

Assistant Professor, Department of Medicine
Columbia University Medical Center