Andy Hudmon
Education
M.S. - 1991 - Interdepartmental Physiology, Auburn University College of Veterinary Medicine
Ph.D. - 1997 - Neurobiology, The University of Texas School of Medicine
Postdoc. 2003 - Neurobiology, Stanford University
Research
See our website for more information: under construction
The long-term goal of the Hudmon laboratory is to elucidate how protein kinases and other effectors function as specialized molecular machines and assemble with their substrates and regulators to form signaling modules in excitable cells like neurons and myocytes. The clinical relevance of these studies hinge upon the role that these signaling complexes play in aberrant calcium signaling; processes that contribute to neurodegeneration following excitotoxicity stimuli like brain trauma and hyperexcitability with chronic pain and lethal arrhythmias in the failing heart. My laboratory focuses on kinases, key signaling molecules downstream of multiple second messengers which represent a significant portion of the druggable effectors being targeted for therapeutic utility. Current research focuses on the Ca2+/calmodulin activated protein kinase (CaMKII); a serine/threonine kinase regulating diverse substrates in response to calcium signaling. While CaMKII is well known for its role as a key mediator of synaptic plasticity and learning/memory, its activity has also been implicated in most organ systems of the body where its substrates are linked to diverse processes. Current research is aimed at understanding how CaMKII contributes to arrhythmogenesis in heart failure through its regulation of voltage-gated sodium and potassium channels as well as understanding how CaMKII signaling contributes to neuronal degeneration and dysfunction during excitotoxicity. Current studies are underway to develop small molecule and highly specific peptides to therapeutically modulate CaMKII in these disease states.
Lab Members
Representative Publications
Ashpole NM, Hudmon A. Excitotoxic neuroprotection and vulnerability with CaMKII inhibition. Molecular and Cellular Neuroscience 2011;46(4):720–730. PMID: 21685929
Ashpole NM, Song W, Brustovetsky T, Engleman EA, Brustovetsky N, Cummins TR, Hudmon A. Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibition induces neurotoxicity via dysregulation of glutamate/calcium signaling and hyperexcitability. Journal of Biological Chemistry 2012; 287(11):8495–8506. PMID: 22253441
Ashpole NM, Herren AW, Ginsburg KS, Johnson DA, Brogan JD, Cummins TR, Bers DM, Hudmon A. CaMKII regulates cardiac sodium channel Nav1.5 by phosphorylation in the loop between domain I and II. J Biol Chem 2012; 287(24):19856–19869.
Tang Q, Bangaru MLY, Wu Hsiang-En, Koopmeiners AS, Kostic S, Pan B, Yu H, Fischer GJ, McCallum JB, Kwok WM, Hudmon A, Hogan QH. Ca2+-dependent regulation of Ca2+ currents in rat primary afferent neurons: Role of CaMKII and the effect of injury. J Neuroscience 2012; 32(34):11737–11749. PMID:22915116
Song W, Yucheng X, Hanying C, Ashpole NM, Piekarz A, Ma P, Hudmon A, Cummins TR, Shou W. Human Nav1.5 F1486 deletion associated with long QT syndrome leads to impaired sodium channel inactivation and reduces lidocaine sensitivity. J Physiol 2012; 590(Pt 20):5123–5139. PMID:22826127.
Ashpole NM, Chawla AR, Martin MP, Brustovetsky T, Brustovetsky N, Hudmon A. Loss of calcium/calmodulin-dependent protein kinase II activity in cortical astrocytes decreases glutamate uptake and induces neurotoxic release of ATP. Journal of Biological Chemistry 2013; May 17;288(20):14599–611. PMID: 23543737
Yu H, Pan B, Weyer A, Wu HE, Meng J, Fischer G, Vilceanu D, Light AR, Stucky C, Rice FL, Hudmon A, Hogan Q. CaMKII controls whether touch is painful. J Neurosci. 2015 Oct 21;35(42):14086–102. PMID: 26490852
Gaji RY, Johnson DE, Treeck M, Wang M, Hudmon A, Arrizabalaga G. Phosphorylation of a myosin motor by TgCDPK3 facilitates rapid initiation of motility during toxoplasma gondii egress. PLoS Pathog. 2015 Nov 6;11(11):e1005268. PMID:26544049
Zhou C, Ramaswamy SS, Johnson DE, Vitturi DA, Schopfer FJ, Freeman BA, Hudmon A, Levitan ES. novel roles for peroxynitrite in angiotensin II and CaMKII signaling. Sci Rep. 2016;6:23416. PMID: 27079272
Pei Z, Xiao Y, Meng J, Hudmon A, Cummins TR. Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation. Nat. Commun. 2016;7:12035. PMID: 27337590
Malty RH, Hudmon A, Fehrenbacher JC, Vasko MR. Long-term exposure to PGE2 causes homologous desensitization of receptor-mediated activation of protein kinase A. J Neuroinflammation. 2016;13(1):181. PMID: 27400965
Chawla AR, Johnson DE, Zybura AS, Leeds BP, Nelson RM, Hudmon A. Constitutive regulation of the glutamate/aspartate transporter EAAT1 by calcium/calmodulin-dependent protein kinase II. J Neurochemistry. 2017;140(3):421–434. PMID: 27889915
Johnson DE, Hudmon A. Activation State-Dependent Substrate Gating in Ca2+/calmodulin-Dependent Protein Kinase II. Neural Plasticity. 2017 In press