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Alexander M. van der Bliek, Ph.D.

Email Address:
avan@mednet.ucla.edu Office Address:
351C BSRB
CAMPUS - 173717
CA
UNITED STATES

Work Address:
Office
Biological Sciences Research Building
Los Angeles, CA 90095
UNITED STATES

Laboratory
Biological Sciences Research Building
Los Angeles, CA 90095
UNITED STATES


Lab Number:
310-206-1755
Office Phone Number:
310-825-9779

Web Address:
Lab Website
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Alexander M. van der Bliek, Ph.D.

Department / Division Affiliations
Professor, Biological Chemistry
Member, Basic/Translational Research, Jonsson Comprehensive Cancer Center, Cell & Developmental Biology GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area, themes

Research Interest:

Cell Biological Studies of Mitochondria in Health and Disease

Mitochondria are often depicted as sausages floating in a sea of cytoplasm. This popular image was overturned by studies of mitochondria in live cells. Time-lapse photography shows many instances of mitochondria dividing or fusing with other mitochondria. Frequent fission and fusion events cause dramatic variations in lengths from small mitochondrial fragments to large connected webs. This dynamic view of mitochondria raises many interesting cell biological questions, which have become the focus of our research.

We discovered that a member of the dynamin family of large GTP binding proteins is required for mitochondrial fission. This dynamin-related protein, named Drp1, is important for normal development, but it also contributes to apoptosis. A major goal of research in our lab is an in-depth understanding of the molecular mechanisms of mitochondrial fission. We focus on the interplay between Drp1 and accessory proteins and on a novel Drp1-independent pathway for mitochondrial fission. In a second line of research, we focus on the functions and regulation of OPA1, which is another dynamin family member, but this one mediates fusion between mitochondria and it helps regulate cytochrome c release from mitochondria during apoptosis. Mutations in OPA1 cause dominant optic atrophy, which is a form of hereditary blindness that occurs through progressive loss of retinal ganglion cells. OPA1 also helps determine whether defective mitochondrial fragments fuse with other mitochondria, which is important for maintaining a healthy mitochondrial network and for diseases such as Parkinson?s. We are focusing on proteolytic regulation of OPA1 and on the mechanisms of OPA1 pathogenesis.

Different members of our lab use C. elegans or cultured mammalian cells to study the fission and fusion processes. C. elegans is used for its wonderful genetic tools and mammalian cells are used for their wealth of biochemical tools. We are currently funded by the NIH and are actively seeking to expand the lab with new students and postdocs. For more information, see our website at vanderblieklab.com.



Biography:

Dr. van der Bliek studied Biology as an undergraduate at the University of Amsterdam. In 1988 he obtained a Ph.D. for studies of multidrug resistance and gene amplification in mammalian cells. These studies were conducted at the Netherlands Cancer Institute under supervision of Dr. Piet Borst. Dr. van der Bliek then worked as a postdoctoral fellow in the lab of Dr. Elliot Meyerowitz at Cal Tech. While there, Dr. van der Bliek discovered the role of dynamin in endocytosis, first in Drosophila and then in mammalian cells (collaboration with Dr. Sandra Schmid at Scripps). In early 1993, Dr. van der Bliek joined the Department of Biological Chemistry at UCLA where his laboratory has maintained an interest in membrane biology with a focus on the cell biological functions of dynamin family members. The lab initially studied the roles of classic dynamins in C. elegans and mammalian cells. In 1999, the van der Bliek lab (and others) discovered the role of dynamin-related proteins in mitochondrial fission. In the following years, the lab has continued to look for novel proteins that are part of the fission machinery. This search recently led to the discovery of a novel mitochondrial fission factor called MFF. In parallel, the lab has investigated the roles of dynamin-related proteins in fusion between mitochondria. This second line of research led to the discovery of enhanced sensitivity to reactive oxygen species in cells lacking fusion proteins and the discovery of a proteolytic cascade controlling mitochondrial fusion in mammalian cells. These findings have relevance for a range of human diseases, including cancer (through apoptosis), eye disease, and Parkinson’s disease.

Publications:

Head Brian P, Zulaika Miren, Ryazantsev Sergey, van der Bliek Alexander M A novel mitochondrial outer membrane protein, MOMA-1, that affects cristae morphology in Caenorhabditis elegans. Molecular biology of the cell. 2011; 22(6): 831-41.
van der Bliek Alexander M, Payne Gregory S Dynamin subunit interactions revealed. Developmental cell. 2010; 18(5): 687-8.
Van der Bliek, A. M. Fussy mitochondria fuse in response to stress. EMBO J 2009; 28: 1533-4.
Head, B., Griparic, L. Amiri, M. Gandre-Babbe, S. & van der Bliek, A. M. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J. Cell Biol 2009; 187: 959-66.
Kanazawa, T., Zappaterra M.D., Hasegawa, A., Wright A.P., Newman-Smith, E.D., Buttle, K., McDonald K.L., Mannella, C.A. & van der Bliek A.M. The C. elegans Opa1 Homologue EAT-3 is Essential for Resistance to Free Radicals. PLoS Genetics 2008; 4: 4, e1000022.
Gandre-Babbe, S. & van der Bliek, A. M. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell 2008; 19: 2402-2412.
Hasegawa, A. & van der Bliek, A.M. Functions of C. elegans and mammalian Mdm38/LetM1 homologues. Hum. Molec. Genet 2007; 16: 2061-2071.
Gandre, S. & van der Bliek, A.M. Mitochondrial division in C. elegans. Methods in Molecular Biology 2007; 372: 485-501.
Griparic, L. Kanzawa , T. & van der Bliek, A.M. Regulation of the mitochondrial dynamin like protein Opa1 by proteolytic cleavage. J. Cell Biol 2007; 178: 757-764.
Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. The Journal of biological chemistry. . 2004; 279(18): 18792-8.
Griparic L, Head B & van der Bliek AM Mitochondrial division and fusion. Topics in Curr. Genet 2004; 8: 227-249.
Smirnova E, Griparic L, Shurland DL, van der Bliek AM Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Molecular biology of the cell. . 2001; 12(8): 2245-56.
Smirnova E, D -L Shurland & AM van der Bliek Mapping Dynamin Interdomain Interactions with Yeast Two-Hybrid and GST-Pulldown Experiments. Methods in Enzymology 2001; 329: 468-477.
Griparic L, van der Bliek AM The many shapes of mitochondrial membranes. Traffic (Copenhagen, Denmark) . 2001; 2(4): 235-44.
Smirnova E, Shurland DL, Newman-Smith ED, Pishvaee B, van der Bliek AM A model for dynamin self-assembly based on binding between three different protein domains. The Journal of biological chemistry. . 1999; 274(21): 14942-7.
van der Bliek AM Functional diversity in the dynamin family. Trends in cell biology. . 1999; 9(3): 96-102.