Mauricio Di Fulvio, Ph.D.
Research Assistant, Wright State University Department of Physiology and Biophysics
Post-doctoral Fellow, WSU Department of Neuroscience, Cell Biology and Physiology
Research Associate, WSU Department of Pharmacology and Toxicology
Visiting Scientist, Children’s Cancer Institute Australia, University of New South Wales, Sydney, Australia
Mechanisms of insulin secretion
Our laboratory is interested in the study of the KATP-independent anionic mechanisms of insulin secretion and how widely used diuretics impact the ability of pancreatic islets to produce insulin and regulate carbohydrate metabolism.
Our research is primarily focused on the molecular biology, gene expression and the regulation of ion transporters targeted by diuretics an how they impact insulin secretion in vitro and in vivo. Basically, our interests are centered at the molecular mechanisms involved in the regulation of transporters' gene expression, the intracellular signaling networks leading to transcriptional or post-transcriptional modulation of their expression and function and how these mechanisms interact to modulate insulin secretion in response to nutrients. We use animal or cellular models, which have been genetically modified to lack or over express genes of interest. We routinely use functional methods to assess glucose homeostasis, tissue function and hormone secretion. Molecular techniques such as the polymerase chain reaction (PCR), reverse transcription coupled to PCR, cloning, sub-cloning, site directed mutagenesis, molecular tagging, gene silencing, gene over expression, and other molecular, immunological and imaging techniques aimed at visualizing gene expression and localization are routinely used in our laboratory to address our research hypotheses.
- Chloride Channels and Transporters in b-cell Physiology. Di Fulvio M, Brown P and Aguilar-Bryan L (2014). In: The Islets of Langerhans. 2nd ed. (2 vol set), 800 p. 240 illus. Editor Md. Shahidul Islam M.D., Ph.D. Karolinska Institutet, Stockholm, Sweden. Springer Netherlands. http://isletbook.islets.se/#home
- A molecular analysis of Na+-independent cation-chloride cotransporters. Gagnon KB and Di Fulvio M (2013). Cell Physiol Biochem 32(S1):14-31.
- Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl– co-transporter-1. Alshahrani S and Di Fulvio M (2012). J Endocrinol 215:59-70.
- Expression of the Slc12a1 gene in pancreatic β-cells: molecular characterization and in silico analysis. Alshahrani S, Alvarez-Leefmans FJ and Di Fulvio M (2012). Cell Physiol Biochem 30:95-112.
- Molecular and functional expression of cation-chloride-cotransporters in dorsal root ganglion neurons during postnatal maturation. Mao S, Garzon-Muvdi T, Di Fulvio M, Chen Y, Delpire E, Alvarez FJ and Alvarez-Leefmans FJ. (2012) J Neurophysiol 108:834-52.
- Rapid determination of the thermal nociceptive threshold in diabetic rats. Alshahrani S, Fernandes-Conti F, Araujo A, Di Fulvio M (2012) J Vis Exp 63:e3785.
- KCC2a expression in a primary fetal human lens epithelial cell line, FHL-12. Lauf PK, Di Fulvio M, Srivastava V, Sharma S and Adragna C. (2012) Cell Physiol Biochem 29:303-312.
- mTOR/S6K down-regulation accelerates myeloid cell differentiation by increasing PLD2 expression and Fes kinase activation. Di Fulvio M, Grunwald W, Cool D, Gomez-Cambronero J. (2012) J Biol Chem 287:393-407.
- mTOR and S6K down-regulate PLD2 basal expression and function. Tabatabaian F, Dougherty K, Di Fulvio M, Gomez-Cambronero J. (2010) J Biol Chem 285:18991-9001.
- PLD2 has both enzymatic and cell proliferation-inducing capabilities that are differentially regulated by phosphorylation and dephosphorylation. Henkels KM, Short S, Peng H-J, Di Fulvio M, Gomez-Cambronero J. (2009) Biochem Biophys Res Commun 389:224-228.
- Tyrosine phosphorylation of Grb2: Role in prolactin/epidermal growth factor crosstalk in mammary epithelial cell growth and differentiation. Haines E, Minoo P, Feng Z, Resalatpanah N, Nie XM, Campiglio M, Alvarez L, Cocolakis E, Ridha M, Di Fulvio M, Gomez-Cambronero J, Lebrun JJ, Ali S. (2009) Mol Cell Biol 29:2505-20.
- Di Fulvio M and Alvarez-Leefmans FJ (2009) The NKCC and NCC genes, an in silico analysis. In: Physiology and Pathology of Chloride Transporters and Channels in the Nervous System. From molecules to diseases. pp. 169-208. Eds. Alvarez-Leefmans FJ & Delpire E. Elsevier. Academic Press, San Diego, CA.
- Mutation of Y179 on phospholipase D2 (PLD2) affects DNA synthesis in a PI3K-dependent manner. Di Fulvio M, Frondorf K, Gomez-Cambronero J. (2008) Cell Signaling 20:176-185.
- Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell chemotaxis and adhesion. Gomez-Cambronero J. (2007) Di Fulvio M, Knapek K. J Leukoc Biol 82:272-281.
- Short-hairpin RNA-mediated stable silencing of Grb2 impairs cell growth and DNA synthesis. Di Fulvio M, Henkels K and Gomez-Cambornero J. (2007) Biochem Biophys Res Commun 357:737-742.
- Phospholipase D (PLD)-derived phosphatidic acid (PA) binds to and activates ribosomal p70S6 kinase (p70S6K). Lehman N, Ledford B, Di Fulvio M, Fordorf K, McPhail L, Gomez-Cambronero J. (2007) FASEB J 21:1075-87.
- The Grb2/PLD2 interaction is essential for lipase activity, intracellular localization and signaling, in response to EGF. Di Fulvio M, Frondorf K, Henkels K, Lehman N, Gomez-Cambronero, J. (2007) J Mol Biol 367:814-24.
- Signal transduction mechanisms of K-Cl cotransport regulation and their relationship to disease. Adragna NC, Ferrell CM, Zhang J, Di Fulvio M, Temprana CF, Sharma A, Fyffe REW, Cool DR, Lauf PK. (2006) Acta Physiologica 187:125-139.
- Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2. Lehman N, Di Fulvio M, McCray N, Campos I, Gomez-Cambronero J. (2006) Blood 108:3564-3572.
- The elucidation of novel SH2 binding sites on PLD2. Di Fulvio M, Lehman N, Lin X, Lopez I, Gómez-Cambronero J. (2006) Oncogene 25:3032-3040.
- Phospholipase D (PLD) gene expression in human neutrophils and HL60 differentiation. Di Fulvio M, Gómez-Cambronero J. (2005) J Leukoc Biol 77:999-1007.
- Regulation of K-Cl cotransport: from function to genes. Adragna NC, Di Fulvio M, Lauf PK. (2004) J Memb Biol 201:109-137.
- Ultrastructural localization of thyroid peroxidase, hydrogen peroxide-generating sites, and monoamine oxidase in benign and malignant thyroid diseases. Masini-Repiso AM, Bonaterra M, Spitale L, Di Fulvio M, Bonino MI, Coleoni AH, Orgnero-Gaisan E. (2004) Hum Pathol 35:436-446.
- The nitric oxide signaling pathway regulates K-Cl cotransporters-3 (KCC3a and KCC3b) expression in vascular smooth muscle cells. Di Fulvio M, Lauf PK, Adragna NC. (2003) Nitric Oxide 9:165-171.
- NONOates regulates potassium-chloride cotransporter-1 and 3 mRNA expression in vascular smooth muscle cells. Di Fulvio M, Lauf PK, Sha S, Adragna NC. (2003) Am J Physiol 284:H1686-1692.
- KCl cotransport regulation and protein kinase G in cultured vascular smooth muscle cells. Adragna, NC, Zhang, J, Di Fulvio, M, Lincoln, TM, Lauf, PK. (2002) J Memb Biol 187:157-165.
- Nitric oxide signaling pathway regulates the potassium-chloride cotransporter-1 mRNA expression in vascular smooth muscle cells. Di Fulvio M, Lauf PK, Adragna NC. (2001) J Biol Chem 276:44534-44540.
- Protein kinase G regulates the potassium-chloride cotransporter (KCC)-4 mRNA expression in primary cultures of rat vascular smooth muscle cells. Di Fulvio M, Lincoln TM, Lauf PK, Adragna NC. (2001) J Biol Chem 276:21046-21052.
- Tri-iodothyronine induces proliferation in cultured bovine thyroid. Evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity. Di Fulvio M, Pellizas CG, Coleoni AH, Masini-Repiso AM. (2000) J Endocrinol 166 173-182.
- Insulin like growth factor-I reduces thyroid hormone receptors in the rat liver. Evidence for a feedback loop regulating the peripheral thyroid hormone action. Pellizas CG, Coleoni AH, Costamagna ME, Di Fulvio M, Masini-Repiso AM. (1998) J Endocrinol 158:87-95, 1998.
- A new point mutation (M313T) in the thyroid hormone receptor b gene in a patient with thyroid hormone resistance. Di Fulvio M, Baranzini S, Chiesa A, Gruñeiro-Papendiek L, Masini-Repiso AM, Targovnik HM. (1997) Thyroid 7:1:43-44.
Clinical Biochemistry, National University of Córdoba, Argentina
Ph.D. Biochemistry, National University of Córdoba, Argentina. Molecular Endocrinology