Research Interests: J.W. Clark Jr.

Research is centered on Computational Engineering in Biology and Medicine. The Clark Laboratory develops detailed mechanistic models of biological processes on several levels of scale: from the nano and micro levels (molecular, cellular and tissue models) to organ and body scale levels (large multiple-organ system models). Examples of cellular models include cardiac and smooth muscle cell models, which contain mechanistic descriptions of ion channels and their modulation via cell signaling systems (e.g., second messengers such as Ca2+, nitric oxide, cAMP and cGMP). Multiple-organ system models include cardiovascular and pulmonary systems for a variety of different species (human, canine, ovine). This work has culminated in the development of a neurally controlled human cardiovascular-respiratory system (H-CVRS) model, which is used to study the interaction between the cardiovascular and pulmonary systems as mediated by the central nervous system (e.g., prediction of cardiopulmonary dynamics during the Valsalva maneuver, orthostasis, cardiac tamponade, pulsus paradoxus and congestive heart failure). This laboratory also develops detailed Hodgkin-Huxley-type models of individual neurons, which are further employed in neural system models, such as those describing the genesis of rhythmic breathing, feedback control of blood pressure and respiration, and quadrupedal gait (the walk, trot and gallop).

Honors:

  • Life Fellow, Institute of Electrical and Electronics Engineers (IEEE), "For Contributions to Modeling in Electrophysiology and Cardiopulmonary Systems", January 2005
  • Founding Fellow of the Biomedical Engineering Society (BMES), Biomedical Engineering Society (BMES), 2005
  • Founding Fellow, American Institute of Medical and Biological Engineering, presented at National Academy of Sciences, Washington, DC, 8 March 1993
  • Fellow, Alexander von Humboldt Foundation, Bonn, Germany. 1975
  • President, IEEE/Engineering in Medicine and Biology Society (EMBS) 2003
  • Past- President, IEEE/Engineering in Medicine and Biology Society (EMBS) 2004
  • IEEE/EMBS Service Award, "For outstanding service and contributions to the EMB Society and a meritorious career in biomedical engineering education."  Presented at 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’09), Minneapolis, MN 2-6 September 2009.
  • Houston Society for Engineering in Medicine and Biology (HSEMB) Special Award, “In recognition of outstanding service to the biomedical engineering community of Houston and for founding the Houston Society for Engineering in Medicine and Biology,” presented at 25th Annual Houston Conference on Biomedical Engineering Research, 7 February 2008.

SELECTED PUBLICATIONS (Molecular and Cellular Modeling):

  • Schild,J.H., J.W. Clark Jr., C.C. Canavier, D.L. Kunze and M.C. Andresen, ``Afferent Synaptic Drive of Rat Medial Nucleus Tractus Solitarius Neurons: Dynamic Simulation of Graded Vesicular Mobilization, Release and non-NMDA Receptor Kinetics,'' Journal of Neurophysiology, 74: 1529-1548, 1995.
  • Butera,R.J., J.W. Clark, Jr., and J.H. Byrne, ``Dissection and Reduction of a Modeled Bursting Neuron,'' Journal of Computational Neuroscience, 3: 199-223, 1996.
  • Lindblad,D.S., C.R. Murphey, J.W. Clark, and W.R. Giles, ``A model of the action potential and underlying membrane currents in a rabbit atrial cell,'' American Journal of Physiology, 271: H1666-H1696, 1996.
  • Demir,S.S., R.J. Butera, A.A. DeFranceschi, J.W. Clark, and J.H. Byrne, ``Phase Sensitivity and Entrainment in a Modeled Bursting Neuron'', Biophysical Journal, 72: 579-594, 1997.
  • Butera, R.J., Clark, J.W. and Byrne, J.H., ``Transient Responses of a Modeled Bursting Neuron: Analysis with Equilibrium and Averaged Nulclines,'' Biological Cybernetics, 77: 307-322, 1997.
  • Nygren,A., C. Fiset, L. Firek, J.W. Clark Jr., D.S. Lindblad, R.B. Clark, and W.R. Giles, ``A Mathematical Model of An Adult Human Atrial Cell: The Role of K+ Currents in Repolarization,'' Circulation Research, 82: 63-81, 1998.
  • Demir,S.S., J.W. Clark and W.R. Giles, ``Parasympathetic Modulation of Sinoatrial Node Pacemaker Activity in Rabbit Heart: A Unifying Model,'' Amer. J. Physiol., 276: H2221-H2244, 1999.
  • Amini, B., Clark, J.W. Jr. and Canavier, C.C., ``Calcium dynamics underlying pacemaker-like and burst firing oscillations in midbrain dopaminergic neurons: A computational study,'' J. Neurophysiology, 82: 2249-2261, 1999.
  • Baxter, D.A., C.C. Canavier, J.W. Clark Jr. and J.H. Byrne, ``Computational Model of the Serotonergic Modulation of Sensory Neurons in Aplysia,'' J. Neurophysiology, 82: 2914-2935, 1999.
  • Athanasiades, A., J.W. Clark Jr., F. Ghorbel and A. Bidani, ``An Ionic Current Model for Medullary Respiratory Neurons,'' J. Computational Neuroscience, J. Computational Neuroscience 9: 237-257, 2000.
  • Sun,L., J-S. Fan, J.W. Clark and P.T. Palade, ``A model of the L-type Ca2+ channel in rat ventricular myocytes: Ion selectivity and inactivation mechanisms,'' J. Physiology, 529: 139-158, 2000.
  • Yang,J., J.W. Clark Jr., R.M. Bryan, and C.S. Robertson, "The myogenic response in isolated rat cerebrovascular arteries: Smooth muscle cell model," Medical Engineering Physics, 25(8): 691-709, 2003.
  • Yang, J., J.W. Clark Jr., R.M. Bryan, and C.S. Robertson, "The myogenic response in isolated rat cerebrovascular arteries: Vessel model," Medical Engineering Physics, 25(8): 711-717, 2003.
  • Amini, B., A. Bidani, J.B. Zwischenberger, and J.W. Clark, Jr., "A model of the rat phrenic motor neuron," IEEE Trans. on Biomed. Engr., 51: 1103-1114, 2004.
  • Luo, C., J.W. Clark, J., T.A. Heming, and A. Bidani, "A simplified model for V-ATPase H+ extrusion," IEEE Trans. on Nanobioscience, 3(4): 257-264, 2004.
  • Yang, J., J.W. Clark Jr., R.M. Bryan, and C.S. Robertson, "Mathematical Modeling of the Nitric Oxide/cGMP Pathways in the Vascular Smooth Muscle Cell," Amer. J. Physiology, 289: H886-H897, 2005.
  • Amini B., A. Bidani, J.B. Zwischenberger, and J.W. Clark, Jr., "A Model of the Pacemaking Neuron of the Respiratory Central Pattern Generator," IEEE Trans. on Neural Systems and Rehabilitation Engineering, 13(2): 120-124, 2005.
  • Luo, C., J.W. Clark Jr., T.A. Heming, A. Bidani, "A Macrophage Cell Model for pH and Volume Regulation," J. Theoretical Biology, 238: 449-463, 2006.
  • Krishna A., L. Sun, M. Valderrabano, P.T. Palade P, J.W. Clark Jr., “Modeling CICR in Rat Ventricular Myocytes: Voltage Clamp Studies,” J. Theoretical Biology and Medical Modeling 2010 Nov. 10; 7:43. PMID: 21062495
  • Krishna,A., M. Valderrabano, P.T. Palade and J.W. Clark Jr., "Multiphysics Model of a Rat Ventricular Myocyte: A Voltage-Clamp Study," J. Theoretical Biology and Medical Modeling 2012, Nov 21; 9(1):48  PMID: 23171697

 

SELECTED PUBLICATIONS (Organ System Modeling):

  • D.C. Chung, S.C. Niranjan, J.W. Clark, Jr., A.Bidani, W.E. Johnston, J.B. Zwischenberger, and D.L. Traber, ``A Dynamic Model of Ventricular Interaction and Pericardial Influence,'' American Journal of Physiology, 272: H2942-2962, 1997.
  • C.H. Liu, S.C. Niranjan, J.W. Clark, Jr., K.Y. San, J.B. Zwischenberger, and A. Bidani, ``Airway Mechanics, Gas Exchange and Blood Flow in a Nonlinear Model of the Human Lung,'' Journal of Applied Physiology, 84: 1447-1469, 1998.
  • J.W. Clark, ``The Origin of Biopotentials,'' in Medical Instrumentation: Application and Design, 3rd edition, edited by J.G. Webster, John Wiley and Sons, Inc., New York, NY Chap. 4, pp. 121-182, 1998.
  • C.C. Canavier, R.J. Butera, R.O. Dror, D.A. Baxter, J.W. Clark and J.H. Byrne, ``Phase Response Characteristics of Model Neurons Determine Which Patterns Are Expressed in a Ring Circuit Model of Gait Generation,'' Biological Cybernetics, 77: 367-380, 1997.
  • J.B. Olansen, F. Ghorbel, J.W. Clark Jr., D. Deyo, J.B. Zwischenberger, and A. Bidani, ``An Automated LabVIEW-Based Data Acquisition System for Analysis of Pulmonary Function,'' J. Clinical Engineering, 23: 279-287, 1998.
  • R.O. Dror, C.C. Canavier, R.J. Butera, J.W. Clark and J.H. Byrne, ``A Mathematical Criterion Based on Phase Response Curves for Stability in a Ring of Coupled Oscillators,'' Biological Cybernetics, 80: 11-23 , 1999.
  • C.C. Canavier, D.A. Baxter, J.W. Clark and J.H. Byrne, "Control of multistability in ring circuits of oscillators", Biological Cybernetics 80: 87-102, 1999.
  • Niranjan, S.C., Bidani, A., Ghorbel, F., Zwischenberger, J.B. and Clark Jr., J.W., ``Analysis of Inspiratory Waveforms on Pulmonary Blood Flow and Gas Exchange During Mechanical Ventilation,'' Computers in Biomedical Research, 32: 355-390, 1999.
  • D.A. Baxter, H.A. Lechner, C.C. Canavier, R.J. Butera, A.A. DeFranceschi, J.W. Clark, and J.H. Byrne, ``Coexisting Stable Oscillatory States in Single Cell and Multi cellular Neuronal Oscillators,'' in Oscillations in Neural Systems, D.S. Levine V.R. Brown, and V.T. Shirley, eds., L. Erlbaum Associates, Mahwah, NJ, 51-77, 1999.
  • Olansen, J.B., Clark, J.W., Khoury, D., Ghorbel, F. and Bidani, A., ``A closed-loop model of the canine cardiovascular system that includes ventricular interaction,'' Computers and Biomedical Research, 33: 260-295, 2000.
  • Athanasiades, A., F. Ghorbel, J.W. Clark Jr., S.C. Niranjan, J. Olansen, J.B. Zwischenberger, and A. Bidani, `` Energy Analysis of a Nonlinear Model of the Normal Human Lung,'' J. Biological Systems 8: 115-139, 2000.
  • Lu, K., J.W. Clark Jr., F.H. Ghorbel,D.L. Ware, and A. Bidani,"A human cardiopulmonary system model applied to the analysis of the Valsalva maneuver," Amer. J. Physiol., 281: H2661-H2679, 2001.
  • Lu, K., J.W. Clark Jr., F.H. Ghorbel, D.L. Ware, J.B. Zwischenberger, and A. Bidani, "Whole-body gas exchange in human predicted by a cardiopulmonary model,"Cardiovascular Engineering, 3: 1-19, 2003.
  • Lu, K., J.W. Clark Jr., F.H. Ghorbel, C.S. Robertson, D.L. Ware, J.B. Zwischenberger, and A. Bidani,"Cerebral autoregulation and gas exchange studied with a human cardiopulmonary model," Amer. J. Physiol.,286: H584-H601, 2004.
  • C. Luo, J.W. Clark Jr., A.A. DeFranceschi, C.C. Canavier, D.A. Baxter and J.H. Byrne, "Multimodal behavior in a four neuron ring circuit: Mode switching," IEEE Trans. on Biomed. Engr., 51(2): 205-218, 2004.
  • Ha, R.R., J. Qian, D.L. Ware, J.B. Zwischenberger, A. Bidani, and J.W. Clark Jr.,"An integrative cardiovascular model of the standing and reclining sheep,"J. Cardiovascular Engineering, 5(2): 53-76, 2005.
  • Ha, R.R., D. Wang, J.B. Zwischenberger and J.W. Clark Jr.,"Hemodynamic Analysis and Design of a Paracorporeal Artificial Lung Device,"Cardiovascular Engineering, 6(1): 10-29, 2006.
  • Luo, C., D. L. Ware, J. B. Zwischenberger and J. W. Clark Jr.,  “Using a Human Cardiopulmonary Model to Study and Predict Normal and Diseased Ventricular Mechanics, Septal Interaction, and Atrio-Ventricular Blood Flow Patterns,” J. Cardiovascular Engineering. 7:17–31, 2007.
  • Luo, C., D. L. Ware, J. B. Zwischenberger and J. W. Clark Jr., “A Mechanical Model of the Human Heart Relating Septal Function to Myocardial Work and Energy, J. Cardiovascular Engineering 8(3):174-184, 2008.
  • D. Ramachandran, C. Luo, T.S. Ma and J.W. Clark, Jr., Using a Human Cardiovascular-Respiratory System Model to Characterize Cardiac Tamponade and Pulsus Paradoxus, J. Theoretical Biology and Medical Modeling 2009 Aug 6;6:15.
  • C. Luo, D. Ramachandran, T.S. Ma and J.W. Clark, Jr.,” Modeling Left Ventricular Diastolic Dysfunction: Classification and Key Indicators,” J. Theoretical Biology and Medical Modeling. 2011 May 9;8:14. PMID: 21554684
  • Ramachandran, D.P., C. Luo, T.S. Ma, and J.W. Clark, Jr., “Modeling Study of the Failing Heart and its Interaction with an Implantable Rotary Blood Pump,”  Conf. Proc. IEEE Eng. Med. Biol. Soc. Aug; 2011: 2403-2409. PMID: 22254826

SELECTED PUBLICATIONS (Medical Imaging):

  • Yue,Y. M.M. Croitoru, A. Bidani, J.B. Zwischenberger, and J.W. Clark, Jr., "Nonlinear Multiscale Wavelet Diffusion for Speckle Suppression and Edge Enhancement in Ultrasound Images," IEEE Trans. Medical Imaging 25(3): 297-311, 2006.
  • Qiao,F., T. Pan, J.W Clark Jr. and O.R. Mawlawi, "A Motion-incorporated Reconstruction Method for Gated PET Studies," Phys. Med. Biol. 51: 3769–3783, 2006.
  • Qiao F, T. Pan, J.W. Clark Jr and O.R. Mawlawi, “Joint Model of Motion and Anatomy for PET image Reconstruction,” Med. Physics, 34(12):4626-4639, 2007.
  • Qiao F, T. Pan, J.W. Clark Jr and O.R. Mawlawi, "Region of Interest Motion Compensation for PET Image Reconstruction,” Phys. Med. Biol. 52(10): 2675-89, 2007.
  • Chang , G., T. Pan, J.W. Clark Jr and O.R. Mawlawi, "Optimization of Super-resolution Processing Using Incomplete Image Sets in PET Imaging," Med. Phys. 35(12):5748-5757, 2008
  • Yue, Y., J.W. Clark Jr. and D. Khoury, “Speckle Tracking in Intracardiac Echocardiography for the Assessment of Myocardial Deformation,” IEEE Trans. on Biomed. Engr.  56(2):416-425, 2009.
  • Chang, G., T. Pan, F. Qiao, J.W. Clark Jr. and O.R. Mawlawi, "Comparison Between Two Super-resolution Implementations in PET Imaging,"  Med. Phys. 36(4):1370-1383, 2009.
  • Chang G., T. Chang, T. Pan, J.W. Clark Jr., O.R. Mawlawi, “Implementation of an Automated Respiratory Amplitude Gating Technique for PET/CT: Clinical Evaluation,”     J. Nucl Med. 2010 Jan;51(1):16-24. Epub 2009 Dec 15.
  • Chang G., T. Chang, J.W. Clark Jr, O.R. Mawlawi, “Design and Performance of a Respiratory Amplitude Gating Device for PET/CT Imaging,” Med. Phys. 2010 Apr; 37(4):1408-12.
  • Chang G., T. Chang, T. Pan, J.W. Clark Jr, O.R. Mawlawi, “Joint Correction of Respiratory Motion Artifact and Partial Volume Effect in Lung/Thoracic PET/CT Imaging,”  Med. Phys. 2010 Dec;37(12):6221-32.
  • Chang G., T. Chang, T. Pan, J.W. Clark, O.R. Mawlawi, “Determination of Internal Target Volume from a Single Positron Emission Tomography/Computed Tomography Scan in Lung Cancer,” Int. J. Radiat. Oncol. Biol. Phys.  2011 Dec 22. PMID:  22197228
  • Chang T., G. Chang, S. Kohlmyer, J.W. Clark, E. Rohren, O.R. Mawlawi, “Effects of Injected Dose, BMI and Scanner Type on NECR and Image Noise in PET Imaging.” Phys. Med. Biol. 2011 Aug 21; 56(16):5275-85.  PMID: 21791730
  • Chang,T., G. Chang, J.W. Clark, R.H. Diab, E. Rohren, O,R. Mawlawi, "Reliability of Predicting Image Signal-to-Noise Ratio Using Noise Equivalent Count Rate in PET Imaging," Med Phys. 2012 Oct;39(10):5891-900. PMID: 23039628
  • Chang,T., G. Chang, J.W Clark Jr., E.M. Rohren, O.R.  Mawlawi,  "A Software Tool for Stitching Two PET/CT Body Segments into a Single Whole-body Image Set," J. Appl. Clin. Med. Phys. 2012 May 10;13(3):3599. PMID: 22584164