B.S., B.A., The University of Texas, 1981
M.D., Ph.D., Baylor College of Medicine, 1988
Fellow in Medical Genetics, Baylor College of Medicine, 1990
Resident in Pediatrics, Baylor College of Medicine, 1992

RESEARCH INTERESTS:
Mitochondrial function: One area of interest is in understanding the role of the mitochondrial outer membrane permeability in the regulation of cellular energy economy, programmed cell death (apoptosis) and mammalian organ function. Voltage-dependent Anion Channels (VDAC1-3 - also known as mitochondrial porins) are a family of mitochondrial outer membrane proteins that conduct small molecules across the outer membrane. VDACs also bind cytosolic kinases such as hexokinases and glycerol kinase, and may be a component of the permeability transition pore, a multi-protein nonselective pore that opens in response to cellular injury. One isoform (VDAC2) functions in suppressing apoptosis by binding the multi-domain pro-apoptotic protein BAK, while other isoforms play roles in glucose metabolism, learning and memory, and fertility. Using model organisms, including mice and flies, we are interested in determining the specific functions of each isoform in biology and relating VDAC function to disease states. These studies involve biochemical, physiologic, and genetic experimentation.

Human Metabolic disorders: Others projects in the laboratory involve studies of metabolic pathways leading to human inherited disorders. Using mutant mice, our current studies are designed to understand the metabolic disturbances that are associated defects in phospholipid and fatty acid metabolism, purine and creatine synthesis, ureagenesis and respiratory chain activities. We are interested in defining cell type-specific functions for the enzymes of intermediary metabolism using knockout mice in conjunction with tissue-specific transgene expression.

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SELECTED PUBLICATIONS:
1. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007). Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat. Cell Biol. 9: 550-555.

2. Anflous-Pharayra K, Cai ZJ, Craigen WJ (2007). VDAC1 serves as a mitochondrial binding site for hexokinase in oxidative muscles. Biochim. Biophys. Acta. 1767: 136-142.

3. Sabirov RZ, Sheiko T, Liu H, Deng D, Okada Y, Craigen WJ (2006). Genetic demonstration that the plasma membrane maxianion channel and voltage-dependent anion channels are unrelated proteins. J. Biol. Chem. 281: 1897-1904.

4. Graham BH, Craigen WJ (2005). Mitochondrial voltage-dependent anion channel gene family in Drosophila melanogaster: Complex patterns of evolution, genomic organization, and developmental expression. Mol. Genet. Metab. 85: 308-317.

5. Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (2003). VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301: 513-517.

6. Sutton VR, Pan Y, Davis EC, Craigen WJ (2003). A mouse model of argininosuccinic aciduria: Biochemical characterization. Molec. Genet. Metab. 78: 11-16.

7. Weeber EJ, Levy M, Sampson MJ, Anflous K, Armstrong D, Brown SE, Sweatt JD, Craigen WJ (2002). The role of mitochondrial porins and the permeability transition pore in learning and synaptic plasticity. J. Biol. Chem. 277: 18891-18897.

8. Sampson MJ, Decker WK, Beaudet AL, Ruitenbeek W, Armstrong D, Hicks MJ, Craigen WJ (2001). Immotile sperm and infertility in mice lacking mitochondrial voltage-dependent anion channel type 3. J. Biol. Chem. 276: 39206-39212.

9. Anflous K, Armstrong D, Craigen WJ (2001). Altered mitochondrial sensitivity for ADP and maintenance of creatine stimulated respiration in oxidative striated muscles from VDAC1 deficient mice. J. Biol. Chem. 276: 1954-1960.

For more publications, see listing on Pub Med.

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CLINICAL INFORMATION:
Board Certifications:
Pediatrics
Clinical Genetics and Biochemical Genetics

Primary Focus:
Genetic Disorders, Metabolic Disorders

Professional Organizations:
Member, American Society of Human Genetics
Member, Society for the Study of Inborn Errors of Metabolism
Member, American Society for the Advancement of Science
Member, The Biophysical Society Society for Inherited Metabolic Disorders

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CONTACT INFORMATION:
William J. Craigen, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, T526
Houston, Texas 77030, U.S.A.

Telephone: 713-798-8305
Fax: 713-798-7773
E-mail:

Last modified: 6/2007