Autophagy is an evolutionarily conserved pathway that involves the lysosomal degradation of long-lived cellular proteins and organelles. Our laboratory identified the first mammalian autophagy protein, Beclin 1, in a screen for novel proteins that interact with the apoptosis inhibitor, Bcl-2. Work by our laboratory and others has established that autophagy participates in a number of fundamental biological processes and diseases. Using genetic approaches in different model organisms, we have shown that beclin 1 and autophagy function in tumor suppression in development and lifespan extension, and in innate antiviral immunity. We have also found that the Bcl-2/Beclin 1 complex provides rheostatic control on autophagy and cell death. Our ongoing research aims to further identify the precise role of autophagy in antimicrobial host defense, in cancer biology, in cell death regulation, and in the prevention of aging and neurodegenerative diseases. To accomplish this goal, we are using a combination of biochemistry, structural biology, molecular biology, and genetic approaches in yeast, C. elegans, and mammalian systems.
RESEARCH INTERESTS
Host-Pathogen Interactions
Autophagy in Innate Immunity against Intracellular Pathogens
Autophagy in Cell Death Regulation and Cancer Biology
RECENT PUBLICATIONS
Pattingre S, Tassa A, Qu X, Liang XH, Packer M, Schneider MD, "Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy." Cell, 122:927-939, September 2005
Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan RN, Gilpin C, Levine B., "Autophagy gene-dependent clearance of apoptotic cells during embryonic development." Cell, 128:931-946, March 2007
Orvedahl A, Alexander D, Talloczy Z, Leib DA, Levine B., "HSV-1 ICP34.5 confers neurovirulence targeting the Beclin 1 autophagy protein." Cell Host & Microbe, 1:23-35, March 2007
Levine B., "Autophagy and cancer." Nature, 446:745-757, April 2007
Levine B and Deretic V., "Autophagy in innate and adaptive immunity." Nature Review Immunology, 7:In Press, 2007
SIGNIFICANT PUBLICATIONS
Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B, "Induction of autophagy and inhibition of tumorigenesis by beclin 1." Nature, 402:672-676, December 1999
Melendez A, Talloczy Z, Seaman M, Eskelinen E-L, Hall DH, Levine B., "Autophagy genes are essential for dauer development and lifespan extension in C. elegans." Science, 301:1387-1391, September 2003
Pattingre S, Tassa A, Qu X, Liang XH, Packer M, Schneider MD, Levine B., "Bcl-2 anti-apoptotic proteins inhibit Beclin 1-dependent autophagy." Cell, 122:927-939, September 2005
Orvedahl A, Alexander D, Talloczy Z, Leib DA, Levine B., "HSV-1 ICP34.5 confres neurovirulence by targeting the Beclin 1 autophagy protein." 2007, 1:23-35, March 2007
Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan RN, Gilpin C, Levine., "Autophagy gene-dependent clearance of apoptotic cells during embryonic development." Cell, 128:931-946, March 2007
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