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Peter W. Stacpoole, MD

Peter W. Stacpoole, MD, PhD
Professor of Medicine
Professor of Biochemistry and Molecular Biology

TEL: (352) 273-9023
FAX: (352) 273-9013

 

 

 

Dr. Stacpoole received his Ph.D. in 1972, from the University of California at San Francisco. He received his MD degree in 1976, from Vanderbilt University in Nashville, Tennessee. He also completed his internship and residency (1976-1978) training in Internal Medicine and Endocrinology Fellowship (1978-1980) training at Vanderbilt University. In 1980, Dr. Stacpoole became a member of the Department of Medicine at the University of Florida where he is currently a Professor of Medicine, Biochemistry and Molecular Biology.

Degree/Program

Institution

Field/Specialty

BS

University of South Sewanee, TN

Chemistry

PhD

University of California

Pharmacology

Post-doctoral training

University of California

Metabolic Research

MD

Vanderbilt University

Medicine

Residency

Vanderbilt University

Internal Medicine

Fellowship

Vanderbilt University

Endocrinology Medicine

Academic/Research Interests:

Dr. Stacpoole’s federally-sponsored research is broadly focused in two areas: intermediary metabolism and new drug development. He conducts patient oriented research on the Shands Hospital Clinical Research Center (CRC) and collaborates with investigators across N. America into the causes and treatment of genetic mitochondrial diseases, due to nuclear DNA or mitochondrial DNA mutations in genes that encode enzymes of carbohydrate metabolism or oxidative phosphorylation. These studies also engage collaborators with expertise in neurology, neurobehavior, clinical pharmacology, neuroscience and cell and molecular biology.

Related research includes mechanistically oriented laboratory studies on the molecular and biochemical consequences of loss-of-function mutations in the mitochondrial pyruvate dehydrogenase complex (PDC) and therapeutic interventions for PDC deficiency. He also collaborates with other faculty at the University of Florida to investigate the regulation of homocystine metabolism in humans in response to different genotypes or nutritional perturbations.

With regard to new drug development, Dr. Stacpoole and his colleagues have developed a prototype for a novel class of investigational drugs for the treatment of acquired or inborn errors of mitochondrial energy metabolism and lactic acidosis. The prototype of this class, dichloroacetate (DCA), is undergoing clinical trials on the CRC in healthy subjects and in children and adults with congenital lactic acidosis. Its sites and mechanisms of action are being further explored by in vitro and in vivo laboratory studies employing cell and molecular techniques and mass spectrometry.

Selected publications (from most recent):

  1. Stacpoole PW, Gilbert LR, Neiberger RE, Carney PR, Valenstein E, Theriaque DW, Shuster JJ.  Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate.  Pediatrics, 121:e1223-e1228, 2008.
  2. Han Z, Berendzen K, Zhong L, Surolia I, Chouthai N, Zhao W, Maina N, Srivastava A, Stacpoole PW. A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate.  Mol Genet Metab 93:381-387, 2008.
  3. Han Z, Zhong L, Srivastava A, Stacpoole PW.  Pyruvate dehydrogenase complex deficiency due to uribuitination and proteasome-mediated degradation of the E1β subunit.  J Biol Chem 4283:237-43, 2008.
  4. Lamers Y, Williamson J, Ralat M, Quinlivan EP, Gilbert LR, Keeling C, Stevens RD, Newgard CB, Ueland PM, Meyer K, Fredriksen A, Stacpoole PW, Gregory JF. Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women.  J Nutr, 139: 452-60, 2009.
  5. Langraf RR, Prieto Conaway MC, Garrett TJ, Stacpoole PW, Yost RA. Imaging of Lipids in Spinal Cord Using Intermediate Pressure Matrix-Assisted Laser Desorption-Linear Ion Trap/Orbitrap MS. Anal Chem, 81(20):8488-95, 2009.
  6. Glushakova LG, Lisankie MJ, Eruslanov EB, Ojano-Dirain C, Zolotukhin I, Liu C, Srivastava A, Stacpoole PW. High-efficiency transduction of human hepatoblastoma and hepatocellular carcinoma cells by AAV3 serotype vectors:  metabolic remodeling and apoptosis following gene transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene.  Mol Genet Metab, 98(3):289-99, 2009.
  7. Ojano-Dirain C, Glushakova LG, Zhong L, Zolotukhin S, Muzyczka N, Srivastava A, Stacpoole PW. An animal model of PDH deficiency using AAV8-siRNA vector-mediated knockdown of pyruvate dehydrogenase E1α. Mol Genet Metab, 101(2-3):183-91, 2010.
  8. Li W, James MO, McKenzie SC, Calcutt NA, Liu C, Stacpoole PW. Mitochondrion as a novel site of dichloroacetate biotransformation by glutathione transferase zeta 1. J Pharmacol Exp Ther 336:87-94, 2010.
  9. Shroads AL, Langaee T, Coats BS, Kurtz TL, Bullock JR, Weithorn D, Gong Y, Wagner DA, Ostrov DA, Johnson JA, Stacpoole PW.  Human polymorphisms in the glutathione transferase zeta 1 maleylacetoacetate isomerase gene predict the kinetics and toxicity of dichloroacetate. J Clin Pharmacol, In press, PMID 21642471.
  10. Glushakova LG, Judge SP, Cruz A, Pourang D, Mathews CE, Stacpoole PW. Increased superoxide accumulation in pyruvate dehydrogenase complex deficient fibroblasts. Mol Genet Metab. 104:255-60, 2011.

 

Please click here for a list of Dr. Stacpoole’s industry relationships.