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Bradley J Stith

TitleProfessor
InstitutionUniversity of Colorado Denver - Denver Campus
DepartmentCLAS-Biology
Phone303/315-7669

    Collapse Biography 
    Collapse awards and honors
    2009Excellence in Research Award, College of Liberal Arts and Sciences, University of Colorado Denver
    2008Faculty Award for Outstanding Student Mentoring; Research and Creative Activities Symposium, University of Colorado Denver
    2007Excellence in Service Award, College of Liberal Arts and Sciences, University of Colorado Denver

    Collapse Overview 
    Collapse overview
    We have suggested a new step in fertilization involving Src tyrosine kinase activation by a lipid called phosphatidic acid (PA). Large-scale HPLC/ELSD quantification of lipids at fertilization (Petcoff et al. J Lipid Res 2365-78, 2008) suggests that production of PA through the action of phospholipase D has a role in fertilization. In an action that requires intact membrane rafts, PA activates Src tyrosine kinase, which then activates phospholipase C (PLC?) to produce IP3 and subsequent intracellular calcium release to induce fertilization in Xenopus laevis (Stith, Developmental Biology 401(2):188–205; Bates et al., Developmental Biology 386:165-180, 2014).
    This work suggests a new path to cancer as PA is elevated and Src is hyperactivated in many forms of cancer. Based on our lipid-Src binding work, studies by Stuart McLaughlin (SUNY Stony Brook) and Miguel Pons (Univ of Barcelona), anionic lipids may bind to the SH4 domain, the ULBR and SH3 domains of Src to “loosen” the tight configuration of Src to lead to its activation. Support: NIH (HD065661) and the University of Colorado Denver Undergraduate Research Opportunity Program


    Collapse Research 
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    F32HD006636     (STITH, BRADLEY J)Jul 15, 1985
    NIH/NICHD
    PROTEIN PHOSPHATE/TYR-KINASE REGULATION BY INSULIN
    Role: Principal Investigator

    R15HD052546     (STITH, BRADLEY J)May 1, 2006 - May 12, 2008
    NIH/NICHD
    Role of Phosphatidic Acid in the Sperm Acrosome Reaction
    Role: Principal Investigator

    R15HD065661     (STITH, BRADLEY J)May 1, 2010 - Sep 30, 2013
    NIH/NICHD
    Lipid Signaling During Fertilization
    Role: Principal Investigator

    R15GM122036     (STITH, BRADLEY J)Sep 23, 2016 - Aug 31, 2019
    NIH/NIGMS
    A new model for Src tyrosine kinase activation through lipid phosphatidic acid
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Bates RC, Stith BJ, Stevens KE. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid. J Pharmacol Sci. 2015 Aug; 128(4):193-201. PMID: 26275469.
      View in: PubMed
    2. Stith BJ. Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development. Dev Biol. 2015 May 15; 401(2):188-205. PMID: 25748412; PMCID: PMC4424143.
    3. Bradley J. Stith. Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development. Developmental Biology. 2015; 401:188-205.
    4. Bates RC, Stith BJ, Stevens KE, Adams CE. Reduced CHRNA7 expression in C3H mice is associated with increases in hippocampal parvalbumin and glutamate decarboxylase-67 (GAD67) as well as altered levels of GABA(A) receptor subunits. Neuroscience. 2014 Jul 25; 273:52-64. PMID: 24836856; PMCID: PMC4122271.
    5. Bates RC, Fees CP, Holland WL, Winger CC, Batbayar K, Ancar R, Bergren T, Petcoff D, Stith BJ. Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization. Dev Biol. 2014 Feb 01; 386(1):165-80. PMID: 24269904; PMCID: PMC3922219.
    6. Bates RC, Stith BJ, Stevens KE. Chronic central administration of valproic acid: Increased pro-survival phospho-proteins and growth cone associated proteins with no behavioral pathology. Pharmacol Biochem Behav. 2012 Dec; 103(2):237-44. PMID: 22960225.
      View in: PubMed
    7. Petcoff DW, Holland WL, Stith BJ. Lipid levels in sperm, eggs, and during fertilization in Xenopus laevis. J Lipid Res. 2008 Nov; 49(11):2365-78. PMID: 18577769.
      View in: PubMed
    8. Sato K, Fukami Y, Stith BJ. Signal transduction pathways leading to Ca2+ release in a vertebrate model system: lessons from Xenopus eggs. Semin Cell Dev Biol. 2006 Apr; 17(2):285-92. PMID: 16584903.
      View in: PubMed
    9. Holland W, Morrison T, Chang Y, Wiernsperger N, Stith BJ. Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 01; 67(11):2081-91. PMID: 15135305.
      View in: PubMed
    10. Stith BJ. Use of animation in teaching cell biology. Cell Biol Educ. 2004; 3(3):181-8. PMID: 15526065; PMCID: PMC520841.
    11. Holland WL, Stauter EC, Stith BJ. Quantification of phosphatidic acid and lysophosphatidic acid by HPLC with evaporative light-scattering detection. J Lipid Res. 2003 Apr; 44(4):854-8. PMID: 12562857.
      View in: PubMed
    12. Luria A, Vegelyte-Avery V, Stith B, Tsvetkova NM, Wolkers WF, Crowe JH, Tablin F, Nuccitelli R. Detergent-free domain isolated from Xenopus egg plasma membrane with properties similar to those of detergent-resistant membranes. Biochemistry. 2002 Nov 05; 41(44):13189-97. PMID: 12403620.
      View in: PubMed
    13. Stith BJ, Hall J, Ayres P, Waggoner L, Moore JD, Shaw WA. Quantification of major classes of Xenopus phospholipids by high performance liquid chromatography with evaporative light scattering detection. J Lipid Res. 2000 Sep; 41(9):1448-54. PMID: 10974052.
      View in: PubMed
    14. Morrison T, Waggoner L, Whitworth-Langley L, Stith BJ. Nongenomic action of progesterone: activation of Xenopus oocyte phospholipase C through a plasma membrane-associated tyrosine kinase. Endocrinology. 2000 Jun; 141(6):2145-52. PMID: 10830302.
      View in: PubMed
    15. Morrison T, Waggoner L, Whitworth-Langley L, Stith BJ. Nongenomic Action of Progesterone: Activation of XenopusOocyte Phospholipase C through a Plasma Membrane-Associated Tyrosine Kinase. Endocrinology. 2000 Jun 01; 141(6):2145-2152. PMID: 28201188.
      View in: PubMed
    16. Stith BJ, Woronoff K, Wiernsperger N. Stimulation of the intracellular portion of the human insulin receptor by the antidiabetic drug metformin. Biochem Pharmacol. 1998 Feb 15; 55(4):533-6. PMID: 9514089.
      View in: PubMed
    17. Stith BJ, Woronoff K, Espinoza R, Smart T. sn-1,2-diacylglycerol and choline increase after fertilization in Xenopus laevis. Mol Biol Cell. 1997 Apr; 8(4):755-65. PMID: 9247652; PMCID: PMC276123.
    18. Stith BJ, Goalstone ML, Espinoza R, Mossel C, Roberts D, Wiernsperger N. The antidiabetic drug metformin elevates receptor tyrosine kinase activity and inositol 1,4,5-trisphosphate mass in Xenopus oocytes. Endocrinology. 1996 Jul; 137(7):2990-9. PMID: 8770923.
      View in: PubMed
    19. Stith BJ, Espinoza R, Roberts D, Smart T. Sperm increase inositol 1,4,5-trisphosphate mass in Xenopus laevis eggs preinjected with calcium buffers or heparin. Dev Biol. 1994 Sep; 165(1):206-15. PMID: 8088439.
      View in: PubMed
    20. Stith BJ, Goalstone M, Silva S, Jaynes C. Inositol 1,4,5-trisphosphate mass changes from fertilization through first cleavage in Xenopus laevis. Mol Biol Cell. 1993 Apr; 4(4):435-43. PMID: 8507898; PMCID: PMC300944.
    21. Stith BJ, Goalstone ML, Kirkwood AJ. Protein kinase C initially inhibits the induction of meiotic cell division in Xenopus oocytes. Cell Signal. 1992 Jul; 4(4):393-403. PMID: 1419482.
      View in: PubMed
    22. Stith BJ, Jaynes C, Goalstone M, Silva S. Insulin and progesterone increase 32PO4-labeling of phospholipids and inositol 1,4,5-trisphosphate mass in Xenopus oocytes. Cell Calcium. 1992 May; 13(5):341-52. PMID: 1320459.
      View in: PubMed
    23. Stith BJ, Kirkwood AJ, Wohnlich E. Insulin-like growth factor 1, insulin, and progesterone induce early and late increases in Xenopus oocyte sn-1,2-diacylglycerol levels before meiotic cell division. J Cell Physiol. 1991 Nov; 149(2):252-9. PMID: 1748718.
      View in: PubMed
    24. Stith BJ, Proctor WR. Microinjection of inositol 1,2-(cyclic)-4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, and inositol 1,4,5-trisphosphate into intact Xenopus oocytes can induce membrane currents independent of extracellular calcium. J Cell Biochem. 1989 Jul; 40(3):321-30. PMID: 2550488.
      View in: PubMed
    25. Stith BJ, Maller JL. Induction of meiotic maturation in Xenopus oocytes by 12-O-tetradecanoylphorbol 13-acetate. Exp Cell Res. 1987 Apr; 169(2):514-23. PMID: 3549336.
      View in: PubMed
    26. Maller JL, Pike LJ, Freidenberg GR, Cordera R, Stith BJ, Olefsky JM, Krebs EG. Increased phosphorylation of ribosomal protein S6 following microinjection of insulin receptor-kinase into Xenopus oocytes. Nature. 1986 Apr 3-9; 320(6061):459-61. PMID: 3083266.
      View in: PubMed
    27. Stith BJ, Maller JL. Increased intracellular pH is not necessary for ribosomal protein s6 phosphorylation, increased protein synthesis, or germinal vesicle breakdown in Xenopus oocytes. Dev Biol. 1985 Feb; 107(2):460-9. PMID: 3882483.
      View in: PubMed
    28. Stith BJ, Maller JL. The effect of insulin on intracellular ph and ribosomal protein S6 phosphorylation in oocytes of Xenopus laevis. Dev Biol. 1984 Mar; 102(1):79-89. PMID: 6365656.
      View in: PubMed
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