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Michael                        Duffey

Michael E. Duffey PhD

Department of Physiology and Biophysics

Professor of Physiology and Biophysics; Professor of Medicine

Specialty/Research Focus

Gastroenterology; Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular and Cellular Biology

 
Professional Summary:

Research in my laboratory concerns neurotransmitter and hormone-mediated anion secretion by gastrointestinal secretory tissues like intestinal crypts and liver ducts. I am determining the mechanisms that regulate the basolateral membrane K+ channel, KCNQ1, in anion secretion because these channels play a critical role in secretion by maintaining membrane potential as a driving force for anion exit across the apical cell membrane. Characterization of KCNQ1 K+ channels will help us to understand and remedy defects in anion secretion, especially in diseases like cystic fibrosis. I use electrophysiological techniques, including Ussing chamber, patch-clamp, and Fura-2 fluorescence techniques. I am also studying the mechanisms by which K+ channel antagonists (e.g., Zn2+) block KCNQ1 channels so that anti-secretory, anti-diarrheal drugs can be developed. I have past experience determining the mechanisms by which neurotransmitters regulate K+ channels via inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release transduction pathways. I am also collaborating with Dr. John Crane to define the mechanisms by which Zn2+ inhibits the effects of Enteropathogenic E. coli (EPEC) on epithelial cell death and EPEC-stimulated phosphorylation and activation of the CFTR Cl- channel.

There is considerable controversy concerning the role and basis of GI disorders associated with autism. In collaboration with Drs. Randall Rasmusson and Glenna Bett, I am investigating the mechanistic link between autism susceptibility and abnormal GI function. I propose that disorders of cellular Ca2+ homeostasis play a key role in the GI disorders of autism. Using mouse models derived from Cav1.2 Ca2+ channel defect that produces the human disorder, Timothy Syndrome, I am characterizing muscle tension and electrophysiological properties of the Ca2+ channel in intestinal smooth muscle. This information will lead to new approaches to identify therapeutic targets and treatments for autistic spectrum GI disorders and symptoms.

Education and Training:
  • PhD, Bioengineering, Carnegie-Mellon University (1977)
  • MS, Bioengineering, Carnegie-Mellon University (1969)
  • BS, Mechanical Engineering, University of Iowa (1968)
Employment:
  • Professor, Medicine, University at Buffalo (2001-present)
  • Director of Graduate Studies for Physiology, Physiology and Biophysics, University of Buffalo (2001-present)
  • Professor, Physiology and Biophysics, University at Buffalo (1993-present)

Grants and Sponsored Research:
  • July 2012–June 2014
    Enhancing Host Defenses against Enteropathogenic and Shiga toxigenic E. coli
    NIH
    Role: Co-Investigator
    $415,318

Journal Articles:
  • Malikowski TM, Bosch JB, Min S, Duffey ME, Patel SP. Carbonic anhydrase inhibitors in corneal endothelial transport. Invest Ophthalmol Vis Sci. 2014; 55(4).
  • McCall AD Nelson JW Leigh NJ Duffey ME Lei P Andreadis ST Baker OJ. Growth factors polymerized within fibrin hydrogel promote amylase production in parotid cells. Tissue Engineering. 2013; 19(19-20).
  • Clementi EA, Marks LR, Duffey ME, Hakansson AP, Hakansson A. A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death. J Biol Chem. 2012; 287(32).
  • Bett GC, Lis A, Wersinger SR, Baizer JS, Duffey ME, Rasmusson RL. A Mouse Model of Timothy Syndrome: a Complex Autistic Disorder Resulting from a Point Mutation in Cav1.2. N Am J Med Sci (Boston). 2012; 5(3).
  • Odusanwo O, Chinthamani S, McCall A, Duffey ME, Baker OJ. Resolvin D1 prevents TNF-a-mediated disruption of salivary epithelial formation. Am J Physiol Cell Physiol. 2012; 302(9).
  • Bett GC, Morales MJ, Beahm DL, Duffey ME, Rasmusson R. Ancillary subunits and stimulation frequency determine the potency of chromanol 293B block of the KCNQ1 potassium channel. J Physiol. 2006; 576(Pt 3).
  • Crane JK, Choudhari SS, Naeher TM, Duffey ME. Mutual enhancement of virulence by enterotoxigenic and enteropathogenic Escherichia coli. Infect Immun. 2006; 74(3).
  • Zhu Y, Hua P, Rafiq S, Waffner EJ, Duffey ME, Lance P. Ca2+- and PKC-dependent stimulation of PGE2 synthesis by deoxycholic acid in human colonic fibroblasts.. Am J Physiol Gastrointest Liver Physiol. 2002; 283(3).
  • Crane JK, Olson RA, Jones HM, Duffey ME. Release of ATP during host cell killing by enteropathogenic E. coli and its role as a secretory mediator.. Am J Physiol Gastrointest Liver Physiol. 2002; 283(1).
  • Izu LT, McCulle SL, Ferreri-Jacobia MT, Devor DC, Duffey ME. Vasoactive intestinal peptide-stimulated Cl- secretion: activation of cAMP-dependent K+ channels.. J Membr Biol. 2002; 186(3).
  • Cliff WH, Duffey ME, Packianathan N. Acetylcholine-activated chloride current in the T-84 colonic cell line.. Pflugers Arch-European Journal of Physiology. 1998; 436(1).
  • Li M, Vemulapalli R, Ullah A, Izu L, Duffey ME, Lance P. Downregulation of a human colonic sialyltransferase by a secondary bile acid and a phorbol ester.. Am J Physiol. 1998; 274(3 Pt).
  • Izu L, Li M, DeMuro R, Duffey ME. G proteins activate ionic conductances at multiple sites in T84 cells.. Am J Physiol. 1997; 272(4 Pt).
  • Devor DC, Sekar MC, Frizzell RA, Duffey ME. Taurodeoxycholate activates potassium and chloride conductances via an IP3-mediated release of calcium from intracellular stores in a colonic cell line (T84). J Clin Invest. 1993; 92(5).
  • Devor DC, Duffey ME. Carbachol induces K+, Cl-, and nonselective cation conductances in T84 cells: a perforated patch-clamp study.. Am J Physiol. 1992; 263(4 Pt).
  • Heitlinger LA, Sloan HR, DeVore DR, Lee PC, Lebenthal E, Duffey ME. Transport of glucose polymer-derived glucose by rabbit jejunum.. Gastroenterology. 1992; 102(2).
  • Devor DC, Ahmed Z, Duffey ME. Cholinergic stimulation produces oscillations of cytosolic Ca2+ in a secretory epithelial cell line, T84.. Am J Physiol. 1991; 260(3 Pt).
  • Li M, Hong SK, Goldinger JM, Duffey ME. Interaction of heptanol and pressure on sodium and chloride transport by toad skin.. J Appl Physiol. 1990; 69(5).
  • Duffey ME, Devor DC, Ahmed Z, Simasko SM. Characterization of a membrane potassium ion conductance in intestinal secretory cells using whole cell patch-clamp and calcium ion-sensitive dye techniques.. Methods Enzymol. 1990; 192.
  • Devor DC, Simasko SM, Duffey ME. Carbachol induces oscillations of membrane potassium conductance in a colonic cell line, T84.. Am J Physiol. 1990; 258(2 Pt).
  • Duffey ME, Devor DC. Intracellular pH and membrane potassium conductance in rabbit distal colon.. Am J Physiol. 1990; 258(2 Pt).
  • Park CC, Park JS, Goldinger JM, Duffey ME, Morin R, Hong SK. Hyperbaric oxygen effect on active Na+ transport across isolated toad skin.. Undersea Biomed Res. 1990; 17(1).
  • Matalon S, Beckman JS, Duffey ME, Freeman BA. Oxidant inhibition of epithelial active sodium transport.. Free Radic Biol Med. 1989; 6(6).
  • Goldinger JM, Duffey ME, Morin RA, Hong SK. Ionic basis of short-circuit current in toad skin at high hydrostatic pressure.. Undersea Biomed Res. 1986; 13(3).
  • Duffey ME, Kelepouris E, Peterson-Yantorno K, Civan MM. Microelectrode study of intracellular pH in frog skin: dependence on serosal chloride.. Am J Physiol. 1986; 251(3 Pt).
  • Ferriola PC, Acara MA, Duffey ME. Thiazide diuretics inhibit chloride absorption by rabbit distal colon.. J Pharmacol Exp Ther. 1986; 238(3).
  • Horvath PJ, Ferriola PC, Weiser MM, Duffey ME. Localization of chloride secretion in rabbit colon: inhibition by anthracene-9-carboxylic acid.. Am J Physiol. 1986; 250(2 Pt).
  • Duffey ME. Intracellular pH and bicarbonate activities in rabbit colon.. Am J Physiol. 1984; 246(5 Pt).
  • Hong SK, Duffey ME, Goldinger JM. Effect of high hydrostatic pressure on sodium transport across toad skin.. Undersea Biomed Res. 1984; 11(1).
  • Palant CE, Duffey ME, Mookerjee BK, Ho S, Bentzel CJ. Ca2+ regulation of tight-junction permeability and structure in Necturus gallbladder.. Am J Physiol. 1983; 245(3).
  • Goldinger JM, Duffey ME, Hong SK. Triphenylmethylphosphonium (TPMP+) as a probe for peritubular membrane potential in the kidney slice.. Proc Soc Exp Biol Med. 1983; 173(2).
  • Duffey ME, Hainau B, Ho S, Bentzel CJ. Regulation of epithelial tight junction permeability by cyclic AMP.. Nature. 1981; 294(5840).
  • Frizzell RA, Duffey ME. Chloride activities in epithelia.. Fed Proc. 1980; 39(11).
  • Duffey ME, Thompson SM, Frizzell RA, Schultz SG. Intracellular chloride activities and active chloride absorption in the intestinal epithelium of the winter flounder.. J Membr Biol. 1979; 50(3-4).
  • Duffey ME, Turnheim K, Frizzell RA, Schultz SG. Intracellular chloride activities in rabbit gallbladder: direct evidence for the role of the sodium-gradient in energizing ‘uphill‘ chloride transport.. J Membr Biol. 1978; 42(3).
  • Duffey ME Evans, Fennel D. Cussler, E.L.. Simultaneous diffusion of ions and ion pairs across liquid membranes. Journal of Membrane Science. 1978; 3.
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Contact Information

224 Cary Hall
Buffalo, NY 14214
Phone: (716) 829-3111
Email: duffey@buffalo.edu


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