Mauricio Di Fulvio, Ph.D.
Research Assistant Professor
Campus Address: 216 Health Sciences Building
Phone: (937) 775-5250
E-mail: mauricio.difulvio@wright.edu
Education
Biochemist Degree (1992), National University of Córdoba, Argentina
Ph.D. in Biochemistry (1999), National University of Córdoba, Argentina
Research Interests
1) Role of Na+, K+, 2Cl- cotransporters in diabetic sensory neuropathy.
Diabetes neuropathy is the most common and earliest complication of diabetes mellitus. Approximately 70 percent of all diabetic patients develop some form of neuropathy. Pain, sometimes excruciating, is present in 8-26 percent of all diabetic patients. It is therefore one of the most frequent, dreadful and debilitating consequences of diabetic neuropathy that impacts the quality of life of the diabetic patient. The underlying mechanisms of the painful diabetic neuropathy are not clearly understood. Our research is focused on understanding the molecular and functional properties of ion transport proteins that may be the target of new pain relievers. These proteins are present in nociceptive primary sensory neurons, the nerve cells that transmit signals to the central nervous system that are perceived as pain. We use a diverse array of molecular and functional techniques as well as behavioral analysis aimed at understanding the mechanisms involved in painful diabetic neuropathy.
2) Solute transporters: Molecular biology, signal transduction and regulation of gene expression.
Our research is also focused on the molecular biology, gene expression and regulation of ion transporters in normal and pathological conditions such as diabetes and its complications. Our interests are centered at the molecular mechanisms involved in the regulation of transporters' gene expression, such as intracellular signaling networks leading to transcriptional or post-transcriptional modulation of gene expression and function. To accomplish our objectives we use animal or cellular models which have been genetically modified to lack or over express genes of interest. We routinely use 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 fluorescent techniques aimed at visualizing gene expression or at determining protein function.
Publications
Papers
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.
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.
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, Di Fulvio M, 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.
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.
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 feed-back 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.
Invited Reviews
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, 2007.
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.
Regulation of K-Cl cotransport: from function to genes. Adragna NC, Di Fulvio M, Lauf PK. (2004) J Memb Biol 201:109-137.
Abstracts (Selected)
Evidence for KCC2a expression in a primary human lens epithelial cell line. Srivastava V, Di Fulvio M., Sharma N., Adragna NC., and Lauf PK. Ohio Physiological Society, 25th Annual Meeting Hyatt Regency at the Arcade, Cleveland, Ohio, October 14-15, 2010.
Expression of the renin-angiotensin system in the kidney fibroblast cell line COS7. Di Fulvio M., Chodavarapu H., and Elased KM. Hypertension Sup 1 2010.
Endogenous expression of the renin-angiotensin system in COS7 cells. Leite AP, Chodavarapu H, Weir NM, Quan R, Di Fulvio M, Fiorino P and Elased KE. Abstract book XXV Reunião Anual da Federação de Sociedades de Biologia Experimental (FeSBE). Ribeirão Preto, São Paulo, Brazil, Aug 24-28, 2010.
5'-UTR splicing of NKCC2 transcripts and an additional promoter in the NKCC2 gene. Di Fulvio M, Garzon-Muvdi T, Mao S, and F. Javier Alvarez-Leefmans. Abstract book, Central Research Forum, Boonshoft School of Medicine, WSU. 2009.
Cloning of NKCC2A expressed in dorsal root ganglia and its heterologous expression in cell lines. Di Fulvio M, Garzon-Muvdi T, Raval B, and F Alvarez-Leefmans. Abstract book, Central Research Forum, Boonshoft School of Medicine, WSU. 2009.
PLD2 activates AKT: Evidence of an AKT-PLD2 short-loop feedback mechanism autoregulating DNA synthesis. Di Fulvio M, Gomez-Cambronero J, Frondorf K, Henkels K. FASEB J 21:A621-A621, 2007.
The elucidation of novel SH2 binding sites on PLD2. Di Fulvio M, Lehman N, Lin X, Lopez I, Gomez-Cambronero J. FASEB J Suppl. S958 2006.
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 and Lauf PK. Intl. Symposium, Cell Volume Control in Health and Disease, Copenhagen, DK, 1:10, 2005.
Signal transduction mechanisms of K-Cl cotransport regulation. Adragna NC, Ferrell CM, Zhang J, Di Fulvio M, Temprana CF, Sharma A, Fyffe REW, Cool DR and Lauf PK. The Ohio Physiological Society, 20th Anniversary 1985-2005. pp17. October 2005.
Hyperphosphorylation of the phospholipase D2 (PLD2) isozyme in stable COS7 and HL60 cells expressing the neutrophilic phenotype. Di Fulvio M, Lehman N, Miller M, Gomez-Cambronero J. FASEB J 20:C-C Suppl. S342 2005.
Screening of PLD2 expressed exons in human neutrophils by RT-PCR. Campos I, Di Fulvio M, Gomez-Cambronero J. FASEB J 18:A309-A309 Suppl. S111, 2004.
Phospholipase D gene expression in human neutrophils. Di Fulvio M, Gomez-Cambronero J. FASEB J. 18:C88, 2004.
Detection of a putative new phospholipase D2a mRNA variant expressed in human neutrophils. Di Fulvio M, Gomez-Cambronero J. J. Leukoc. Biol. Suppl 1, 2003.
Platelet derived growth factor (PDGF) regulates K-Cl COT activity and KCC1/KCC3 mRNA expression in vascular smooth muscle cells (VSMCs). Zhang J, Di Fulvio M, Lauf PK, Adragna NC. FASEB J ,16 (Part 1), 2002.
Properties of K-Cl cotransport (COT) in C6 glioma cells. Gagnon KBE, Fyffe EW, Di Fulvio M, Adragna NC, Lauf PK. FASEB J ,16 (Part 2), 2002.
Protein kinase G (PKG) signaling pathway regulates the potassium-chloride cotransporter -3 (KCC3a, and KCC3b) mRNA expression in primary cultures of rat vascular smooth muscle cells (VSMCs). Di Fulvio M, Lauf PK, Adragna NC. FASEB J ,16 (Part 1), 2002.
Thyroid hormone (T3) increases mitogen-activated protein kinases (MAPK) ERK-1 and ERK-2 expression in primary cultures of bovine thyrocytes. Di Fulvio M, Zurita A, Daniotti J, Masini-Repiso A. FASEB J 15(Part 1), 2001.
Thyroid stimulating hormone (TSH) inhibits thyroid hormone (T3)-induced DNA synthesis in primary cultures of bovine thyrocytes. Di Fulvio M, Pellizas CG, Coleoni AH, Masini-Repiso A. FASEB J 15(Part 1), 2001.
Protein kinase G regulates the potassium-chloride cotransporter (KCC)-3 mRNA expression in primary cultures of rat vascular smooth muscle cells (VSMCs). Di Fulvio M, Lauf PK, Adragna NC. FASEB J 15(Part 1), 2001.
Lipid-protein interactions and signal transduction. Adragna NC, Di Fulvio M, Ferrel CM, Lauf PK. Abstract book, First Mercosur Workshop on Biomembranes, 2000.
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. Endocr J 47 (Suppl. 2):159, 2000.
An intronic mutation in the thyroid hormone receptor b gene in a patient with resistance to thyroid hormone. Di Fulvio M, Miras M, Bazzara L, Masini-Repiso A, Targovnik H. Abstract Book IV International Workshop on Thyroid Hormone Resistance Syndrome, 1999.
