Michael E. Duffey PhD

Michael Duffey

Michael E. Duffey
PhD

Professor of Physiology and Biophysics; Professor of Medicine

Department of Physiology and Biophysics

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

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

Contact Information
4154 JSMBS
955 Main Street
Buffalo, NY 14203
Phone: (716) 829-3111
duffey@buffalo.edu



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:

  • February 2018–January 2023
    Investigating the Action and Physiological Role of Slc4a11 in the Cornea
    National Institutes of Health
    Role: Co-Investigator
    $1,972,804
  • July 2012–June 2014
    Enhancing Host Defenses against Enteropathogenic and Shiga toxigenic E. coli
    NIH
    Role: Co-Investigator
    $415,318

Journal Articles:

  • Caitlin Dudley A. Morell M. Duffey S. Patel. Effects of amantadine on corneal endothelium. Exp. Eye Res.. 2019.
  • Gururaj S, Palmer EE, Sheehan GD, Kandula T, Macintosh R, Ying K, Morris P, Tao J, Dias KR, Zhu Y, Dinger ME, Cowley MJ, Kirk EP, Roscioli T, Sachdev R, Duffey ME, Bye A, Bhattacharjee A. A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters Ion Selectivity and Causes Epileptic Encephalopathy. Cell Rep. 2017; 21(4).
  • 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 Eng Part A. 2013.
  • 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.
  • Duffey ME, Devor DC. Intracellular pH and membrane potassium conductance in rabbit distal colon.. Am J Physiol. 1990; 258(2 Pt).
  • 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).
  • 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).
  • Ferriola PC, Acara MA, Duffey ME. Thiazide diuretics inhibit chloride absorption by rabbit distal colon.. J Pharmacol Exp Ther. 1986; 238(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).
  • 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).
  • 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

4154 JSMBS
955 Main Street
Buffalo, NY 14203
Phone: (716) 829-3111
duffey@buffalo.edu