William J. Craigen, M.D., Ph.D.
Professor of Molecular and Human Genetics
B.S., B.A., University of Texas at Austin, 1981
M.D., Ph.D., Baylor College of Medicine, 1988
Fellow, Medical Genetics, Baylor College of Medicine, 1990
Resident, Pediatrics, Baylor College of Medicine, 1992
American Board of Medical Genetics: Clinical Biochemical Genetics and Clinical Genetics
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
Genetic Disorders and Metabolic Disorders
Mitochondrial function: Mitochondria are now recognized to play a variety of important physiologic roles in various processes beyond ATP synthesis, including programmed cell death (apoptosis), retrograde signaling, cellular proliferation, and the regulation of intermediary metabolism. One area of interest in the lab is in understanding the role of the mitochondrial outer membrane permeability in the regulation of cellular energy economy, 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 hexokinase isoforms, and may act to tether other multi-protein complexes to mitochondria. 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 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: Despite advances in identifying human metabolic diseases, pathophysiologic mechanisms are poorly understood and specific treatment strategies lacking. 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, and mitochondrial 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.
- Akman HO, Sheiko T, Tay SK, Finegold MJ, Dimauro S, Craigen WJ (2011). Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV. Hum. Mol. Genet. 20(22): 4430-9. PubMed PMID: 21856731
- Akman HO, Raghavan A, Craigen WJ (2011). Animal models of glycogen storage disorders. Prog. Mol. Biol. Transl. Sci. 100: 369-88. PubMed PMID: 21377631
- Wong LJ, Scaglia F, Graham BH, Craigen WJ (2010). Current molecular diagnostic algorithm for mitochondrial disorders. Mol. Genet. Metab. 100(2): 111-7. PubMed PMID: 20359921
- Roy SS, Ehrlich AM, Craigen WJ, Hajnóczky G (2009). VDAC2 is required for truncated BID-induced mitochondrial apoptosis by recruiting BAK to the mitochondria. EMBO Rep. 10(12): 1341-7. PubMed PMID: 19820692
- 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(5): 550-5. PubMed PMID: 17417626
- Anflous-Pharayra K, Cai ZJ, Craigen WJ (2007). VDAC1 serves as a mitochondrial binding site for hexokinase in oxidative muscles. Biochim. Biophys. Acta. 1767(2): 136-42. PubMed PMID: 17207767
- 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(4): 1897-904. PubMed PMID: 16291750
- Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (2003). VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301(5632): 513-7. PubMed PMID: 12881569
- 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(21): 18891-7. PubMed PMID: 11907043
- 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(3): 1954-60. PubMed PMID: 11044447
William J. Craigen, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.