Thomas Clanton, Ph.D.
Professor
Department of Applied Physiology and Kinesiology
University of Florida
B.A. Chemistry, Gustavus Adolphus College, 1971
Ph.D. Physiology & Biophysics, Univ. of Nebraska Medical School, 1980
Postdoctoral Fellowship, The Ohio State University, 1980-1982
Our laboratory is studying how skeletal and cardiac muscles respond to various forms of stress. Interestingly, compared to other tissues, skeletal muscles see a great variety of stress stimuli. For example, under relatively normal conditions of intense exercise, there are elevations in temperature, reductions in PO2, reductions in pH, osmotic gradients causing shrinkage or swelling, distortions of the cytoskeleton and of the sarcolemmal membrane. Many of these stresses induce an interesting wave of reactive oxygen species (ROS) that appears to be important in the cellular stress response but we do not understand where the ROS are coming from or what role they play in normal physiology. Recently we have been pursuing the influence of these low-level ROS signals on the reaction rates of cell signaling systems, on calcium regulation and on their possible role in O2 or temperature sensing. The low level ROS signals appear to prepare cells for later exposure to stress, a kind of preconditioning phenomenon, but we still know little about how this works and how relevant it is to physiology of intact animals or man.
We are also greatly interested in developing new imaging and spectroscopy methods for evaluating the physiology of cells and tissue. Using unique fluorescent spectroscopy methods, we have observed ROS formation and changes in calcium regulation in intact muscle and heart from animals. These real time measurements are telling us a great deal about how cell systems behave in stress. More recently we have developed fluorescent resonance energy transfer (FRET) methods for compartmentalizing physiological signals within the mitochondria, cytosol or extracellular environment. With the move to the University of Florida in September of 2007, and with tremendous support of the Department and College we are building a state-of-art live cell fluorescent confocal imaging system, representing a $350,000 investment. This will allow us, along with our colleagues within the College to image intact animals, tissues and cells using image collection rates of up to 500 frames per second with very low intensity light. We will utilize this system to observe rapid physiological events such as changes in membrane potential, calcium sparks and enzymatic reactions within individual compartments of cells or in the vasculature in real time.
Another new area we are interested in is to understand the origins of heat stroke and heat related illness. Every year tragic and unexpected deaths occur in young athletes and soldiers from overexertion in heat. We are trying to understand what makes a person susceptible to heat illness and what we might do to predict increased susceptibility in a given person. Our most current experiments involve the study of eicosanoid metabolism, the system responsible for production of lipid mediators such as leukotrienes, prostaglandins and HETEs. We have found that these enzyme systems are incredibly active in hyperthermia and appear to be essential for protection from the effects of relatively low levels of heat exposure. With other colleagues on campus our research group is beginning to build “An integrated program in heat stress biology” at the University of Florida where we will investigate broad questions regarding the physiology and molecular biology of heat exposure and heat adaptation.
Dr. Clanton was trained as a respiratory and neuro-physiologist and has a strong background, interest and practical experience in pulmonary medicine, pathophysiology of pulmonary disease, cardiovascular disease, and in clinical exercise testing and rehabilitation. It is hoped that the basic science problems and biophysical approaches being developed in his lab today will address the systemic disorders caused by cardiopulmonary diseases tomorrow.
For more information: tclanton@hhp.ufl.edu
Clanton, TL, VP Wright, PJ Reiser, PT Klawitter, N Prabhakar. Physiologic and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia. J. Appl. Physiol. 90: 2508-2513, 2001.
Clanton, TL, PF Klawitter. Physiologic and Genomic Consequences of Intermittent Hypoxia: Invited Review: Adaptive responses of skeletal muscle to intermittent hypoxia, the known and the unknown. J. Appl. Physiol. 90: 2476-2487, 2001.
Khramtsov, VK, VA Reznikov, LJ Berliner, AK Litkin, IA Grigor’ev, TL Clanton. NMR spin trapping: detection of free radical reactions with a new fluorinated DMPO analog, in Supramolecular Structure and Function 7, (G. Pifat-Mrzljak, ed, Kluwer Academic/Plenum Publishers, New York) pp. 107-117, 2001.
Zuo, L, TL Clanton Detection of reactive oxygen and nitrogen species in tissues using redox-sensitive fluorescent probes. Methods in Enzymology 325: 307-325, 2002
Bhatt, N.Y. ,Kelley, T.W., Khramtsov V., Wang Y., Lam G.K., Clanton, T.L. , Marsh, C.B. M-CSF-induced Erk activation involves PI 3-kinase and ROS in human monocytes J. Immunol. 169(11):6427-34, 2002
ATS/ERS Statement on Standardization of Respiratory Muscle Tests. T.L. Clanton, lead author of “Tests of Respiratory Muscle Endurance.” Ed. A.Grassino, J.Moxham, Amer J Resp Crit Care Med 166:559-569, 2002
Potapenko, D.G., T.L. Clanton, E.G. Bagryanskaya, N.P Gritsan, V.A. Reznikov, V.V. Kharmtsov. Nonradical mechanism of (bi)sulfite reactions with DEPMPO: cautionary note for SO3•? radical spin trapping. Free Radical Biology & Med, 32 (2), 196 206, 2003
Zuo L, S. Pasniciuc, V.P. Wright, A.J. Merola, T.L. Clanton. Sources for superoxide release: lessons from blockade of electron transport, NADPH oxidase and anion channels in diaphragm. Antioxidants & Redox Signaling, 5(5):667-675, 2003
Klawitter, P.F., H.N.Murray, T.L. Clanton, M.G. Angelos. Reactive oxygen species generated during myocardial ischemia enable energetic recovery during reperfusion. Am J Physiol Heart Circ Physiol 2002 283: H1656-H1661
Diaz PT, Wewers MD, Pacht E, Drake J, Nagaraja HN, Clanton TL. Respiratory symptoms among HIV seropositive individuals. Chest, 123(6):1977-82.2003.
Klawitter, P.F. T.L. Clanton. Tension-time index, fatigue and energetics in isolated rat diaphragm: a new experimental model. J. Appl. Physiol. 96(1):89-95, 2004
Potapenko, D.I., E.G. Bagryanskaya, V.V. Reznikov, T.L. Clanton and V.V. Khramtsov, 2003, NMR and EPR studies of the reaction of nucleophylic addition of (bi)sulfite to the nitrone spin trap DMPO Magn.Reson.Chem. 41:603-608, 2004
Stoner, J., Angelos, M.G., Clanton, T.L. Myocardial contractile function during post-ischemic low flow reperfusion: critical thresholds of NADH and O2 delivery. Am. J. Physiol, Heart and Circulation 286(1):H375-80, 2004.
Bobko, A.A., Bagryanskaya, E.G., Reznikov, V.A., Kolosova, N.G., Clanton, T.L., Khramtosv, V.V., Redox sensitive mechanism for NO scavenging by nitronyl nitroxides. Free Rad. Biol. Med. 36, 248-258,2004.
Zuo, L, F.L. Christofi, V.P. Wright, S. Bao, T.L. Clanton. Lipoxygenase-dependent extracellular superoxide release in skeletal muscle J. Appl Physiol, 97:661-668, 2004
Potapenko, D.I., E.G.Bagrayanskaya, AY.P. Tcentalovich, V.V.Reznikov, T.L. Clanton, V.V. Khramtsov. Reversible reaction of thiols and thiyl radicals with nitrone spin traps. J.Phys.Chem. B 108:9315-9324, 2004.
Diaz PT, Wewers MD, King M, Wade J, Hart J, Clanton TL. Regional differences in emphysema scores and BAL glutathione levels in HIV-infected individuals. Chest. 2004 Nov;126(5):1439-42.
Wright, V.P., Klawitter, P., Iscru, D.F, Merola, A.J., Clanton, T.L. Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm. J. Appl. Physiol 98(5):1753-60, 2005.
Wewers MD, Lemeshow S, Lehman A, Clanton TL, Diaz PT. Lung CD4 lymphocytes predict survival in asymptomatic HIV infection. Chest. 2005 Oct;128(4):2262-7.
Zuo, L., Clanton, T.L. Reactive oxygen formation in the transition to hypoxia in skeletal muscle. Am J Physiol Cell Physiol. 2005 Jul;289(1):C207-16.
Potapennko, D.I., Bagryanskaya, E.G., Grigoriev, I.A., Masimov, A.M., Reznikov, V.A., Platonov, V.E., Clanton, T.L., Khramtsov, V.V. Quantitative determination of SH-groups using 19F NMR spectroscopy and disulphide of 2,3,5,6-tetrafluoro-4-mercapto-benzoic acid Magn Reson Chem. 43(11):902-9, 2005
Clanton, T.L. Invited Editorial: Yet another Oxygen Paradox. J Appl Physiol 99: 1245-1246, 2005
Stoner JD, Clanton TL, Aune SE, Angelos MG, O2 Delivery and redox state are determinants of compartment-specific reactive oxygen species in myocardial reperfusion. Amer. J. Physiol, Heart and Circ. 292(1):H109-16, 2007
Clanton, T.L. Hypoxia-induced reactive oxygen formation, J Appl. Physiol. 102(6):2379-88, 2007