Kenneth Byron, PhD

  • Professor
  • Molecular Pharmacology and Therapeutics
  • Cell and Molecular Physiology

Research in the Byron lab is broadly related to the cellular and biochemical mechanisms that operate to regulate smooth muscle contraction. Smooth muscle is found in many tissues, including the walls of arteries (vascular smooth muscle) and the airways of the lung (airway smooth muscle). In arteries, the ability of smooth muscle cells to contract or relax allows for moment-to-moment control of artery diameter, and hence determines blood flow and blood pressure. A main objective of the research is to elucidate the molecular mechanisms by which vasoactive substances exert their effects, with a long-term goal of identifying improved therapeutic strategies for treatment of cardiovascular diseases. Research from this laboratory over the past 20 years has revealed novel cellular mechanisms that are activated by vasoconstrictor hormones, such as the pituitary hormone arginine vasopressin (AVP). The vasoconstrictor effects of AVP were found to involve inhibition of a specific class of potassium channels that were recognized as drug target in the nervous system. This research has helped explain off-target cardiovascular effects of the drugs when used to treat neurological conditions, and also suggested potential new uses of these drugs to treat cardiovascular conditions. One example of the latter is cerebral vasospasm, a devastating form of stroke that occurs following rupture of a cerebral aneurysm. Dr. Byron’s laboratory is collaborating with Loyola neurosurgeons and neurologists to design a clinical trial to test novel therapies for cerebral vasospasm based on their research on AVP vasoconstrictor mechanisms. In the airways of the lung, smooth muscle contraction can lead to narrowing of the airways, which can become excessive in conditions like asthma, resulting in obstruction of airflow. The Byron lab has found that the same proteins that are targeted by AVP in the vasculature are mediators of bronchoconstrictor actions that increase airway smooth muscle contraction in the lung. Ongoing research is investigating the molecular mechanisms by which airway smooth muscle ion channels contribute to bronchoconstrictor signal transduction, and determining how drugs that target potassium channels in airway smooth muscle might be more effective than currently used drugs in the relief of airflow obstruction in asthma and other airway diseases. In collaboration with clinical pulmonologists at Loyola, Dr. Byron and colleagues are designing a clinical trial to test the efficacy of drugs that target these mechanisms for relief of excessive airway smooth muscle contraction in patients with asthma.

  • Haick,J. M.; Byron,K. L. Novel treatment strategies for smooth muscle disorders: Targeting Kv7 potassium channels Pharmacology & therapeutics 2016 ; :
  • Evans,A. E.; Tripathi,A.; LaPorte,H. M.; Brueggemann,L. I.; Singh,A. K.; Albee,L. J.; Byron,K. L.; Tarasova,N. I.; Volkman,B. F.; Cho,T. Y.; Gaponenko,V.; Majetschak,M.New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle International journal of molecular sciences 2016 ;17(5):10.3390/ijms17060971
  • Mani,B. K.; Robakowski,C.; Brueggemann,L. I.; Cribbs,L. L.; Tripathi,A.; Majetschak,M.; Byron,K. L.Kv7.5 Potassium Channel Subunits Are the Primary Targets for PKA-Dependent Enhancement of Vascular Smooth Muscle Kv7 Currents Molecular pharmacology 2016 ;89(3):323-334
  • Tripathi,A.; Vana,P. G.; Chavan,T. S.; Brueggemann,L. I.; Byron,K. L.; Tarasova,N. I.; Volkman,B. F.; Gaponenko,V.; Majetschak,M.Heteromerization of chemokine (C-X-C motif) receptor 4 with alpha1A/B-adrenergic receptors controls alpha1-adrenergic receptor function Proceedings of the National Academy of Sciences of the United States of America 2015 ;112(13):E1659-E1668
  • Brueggemann,L. I.; Haick,J. M.; Cribbs,L. L.; Byron,K. L.Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5 channels by ML213 and ICA-069673 Molecular pharmacology 2014 ;86(3):330-341
  • Brueggemann,L. I.; Haick,J. M.; Neuburg,S.; Tate,S.; Randhawa,D.; Cribbs,L. L.; Byron,K. L.KCNQ (Kv7) potassium channel activators as bronchodilators: combination with a beta2-adrenergic agonist enhances relaxation of rat airways American journal of physiology.Lung cellular and molecular physiology 2014 ;306(6):L476-86
  • Brueggemann,L. I.; Mackie,A. R.; Cribbs,L. L.; Freda,J.; Tripathi,A.; Majetschak,M.; Byron,K. L.Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels The Journal of biological chemistry 2014 ;289(4):2099-2111
  • Bach,H. H.,4th; Wong,Y. M.; Tripathi,A.; Nevins,A. M.; Gamelli,R. L.; Volkman,B. F.; Byron,K. L.; Majetschak,M.Chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate vascular alpha(1)-adrenergic receptor function Molecular medicine (Cambridge, Mass.) 2014 ;20:435-447
  • Brueggemann,L. I.; Gentile,S.; Byron,K. L.Social networking among voltage-activated potassium channels Progress in molecular biology and translational science 2013 ;117:269-302
  • Mani,B. K.; O'Dowd,J.; Kumar,L.; Brueggemann,L. I.; Ross,M.; Byron,K. L.Vascular KCNQ (Kv7) potassium channels as common signaling intermediates and therapeutic targets in cerebral vasospasm JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 2013 ;61(1):51-62
  • Badri,K. R.; Yue,M.; Carretero,O. A.; Aramgam,S. L.; Cao,J.; Sharkady,S.; Kim,G. H.; Taylor,G. A.; Byron,K. L.; Schuger,L.Blood pressure homeostasis is maintained by a P311-TGF-beta axis The Journal of clinical investigation 2013 ;123(10):4502-4512
  • Brueggemann,L. I.; Mani,B. K.; Haick,J.; Byron,K. L.Exploring arterial smooth muscle Kv7 potassium channel function using patch clamp electrophysiology and pressure myography Journal of visualized experiments : JoVE 2012 ;(67):e4263. doi(67):e4263
  • Brueggemann,L. I.; Kakad,P. P.; Love,R. B.; Solway,J.; Dowell,M. L.; Cribbs,L. L.; Byron,K. L.Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy. American Journal of Physiology - Lung Cellular & Molecular Physiology 2012 ;302(1):120-132
  • Mani,B. K.; Byron,K. L.Vascular KCNQ channels in humans: the sub-threshold brake that regulates vascular tone?. British journal of pharmacology 2011 ;162(1):38-41
  • Brueggemann,L. I.; Mackie,A. R.; Martin,J. L.; Cribbs,L. L.; Byron,K. L.Diclofenac distinguishes among homomeric and heteromeric potassium channels composed of KCNQ4 and KCNQ5 subunits. Molecular pharmacology 2011 ;79(1):10-23
  • Mani,B. K.; Brueggemann,L. I.; Cribbs,L. L.; Byron,K. L.Opposite regulation of KCNQ5 and TRPC6 channels contributes to vasopressin-stimulated calcium spiking responses in A7r5 vascular smooth muscle cells. Cell calcium 2009 ;45(4):400-411
  • Brueggemann,L. I.; Mackie,A. R.; Mani,B. K.; Cribbs,L. L.; Byron,K. L.Differential effects of selective cyclooxygenase-2 inhibitors on vascular smooth muscle ion channels may account for differences in cardiovascular risk profiles. Molecular pharmacology 2009 ;76(5):1053-1061
  • Byron,K. L.; Brueggemann,L. I.Labour pains: giving birth to new mechanisms for the regulation of myometrial contractility Journal of Physiology 2009 ;587(Pt 10):2109-2110
  • Mackie,A. R.; Brueggemann,L. I.; Henderson,K. K.; Shiels,A. J.; Cribbs,L. L.; Scrogin,K. E.; Byron,K. L.Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction by vasopressin, based on studies in single cells, pressurized arteries, and in vivo measurements of mesenteric vascular resistance. Journal of Pharmacology & Experimental Therapeutics 2008 ;325(2):475-483
  • Mackie,A. R.; Byron,K. L.Cardiovascular KCNQ (Kv7) potassium channels: physiological regulators and new targets for therapeutic intervention Molecular pharmacology 2008 ;74(5):1171-1179
  • Henderson,K. K.; Byron,K. L.Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways. Journal of applied physiology 2007 ;102(4):1402-1409
  • Brueggemann,L. I.; Moran,C. J.; Barakat,J. A.; Yeh,J. Z.; Cribbs,L. L.; Byron,K. L.Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells. American Journal of Physiology - Heart & Circulatory Physiology 2007 ;292(3):H1352-63
  • Brueggemann,L. I.; Markun,D. R.; Henderson,K. K.; Cribbs,L. L.; Byron,K. L.Pharmacological and electrophysiological characterization of store-operated currents and capacitative Ca(2+) entry in vascular smooth muscle cells. Journal of Pharmacology & Experimental Therapeutics 2006 ;317(2):488-499
  • Brueggemann,L. I.; Markun,D. R.; Barakat,J. A.; Chen,H.; Byron,K. L.Evidence against reciprocal regulation of Ca2+ entry by vasopressin in A7r5 rat aortic smooth-muscle cells The Biochemical journal 2005 ;388(Pt 1):237-244
  • Brueggemann,L. I.; Martin,B. L.; Barakat,J.; Byron,K. L.; Cribbs,L. L.Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking. American Journal of Physiology - Heart & Circulatory Physiology 2005 ;288(2):H923-35
  • Bayer,A. L.; Heidkamp,M. C.; Howes,A. L.; Heller Brown,J.; Byron,K. L.; Samarel,A. M.Protein kinase C epsilon-dependent activation of proline-rich tyrosine kinase 2 in neonatal rat ventricular myocytes. Journal of Molecular & Cellular Cardiology 2003 ;35(9):1121-1133