1. Peripheral Nervous System
    Our 10-point Agenda/Questions in PAIN Science

  2. BulletMolecular transducers (receptors and/or ion channels) on mammalian sensory neurons that detect pain-producing stimuli, leading to their excitation and electrical signal transmission.

  3. BulletSpecific functions of these transducers that detect pain-producing stimuli in sensory neurons.

  4. BulletChanges in the molecular and cellular properties of these transducers that enable them to become functional at innocuous and minimally pain-producing stimuli, thereby transmitting peripheral electrical signals under painful pathologies.

  5. BulletPathological signaling mediators that induce such functional changes in these transducers, as well as stimulate anatomical changes in sensory nerves.

  6. BulletDistinct and common pathological signaling mediators in multiple pain pathologies, such as metastatic bone cancers, inflammation, arthritis and obesity.

  7. BulletHow these molecular, cellular and anatomical changes that culminate in inducing the overall functional changes in sensory neuron excitation, result in peripheral processing of pain associated with multiple pain pathologies using mouse models.

  8. BulletBone-metastasized breast, prostate  and melanoma cancers

  9. BulletTissue injury, inflammation and arthritis

  10. BulletObesity

  11. BulletIdentification and pre-clinical validation of target pain-transducers for specific pain pathologies.

  12. BulletIn vivo pharmacology in mouse models of chronic pain, and genetic validation by using genetically-modified mice. 

  13. BulletDevelopment/testing of antagonists to target specific modulatory function of these pain-transducers.

  14. BulletFunctional studies on pain transducers and nociceptor excitability in human sensory neurons in culture to seek in vitro translational validation of our mechanistic pain studies from rodents. 

  15.  

  16.  

  17. Central Nervous System
    Survival-Death Dynamics in Mammalian Brain Neurons

  18. The intrinsic excitability of neurons in our body reflects the complex but fine interplay between the inward and outward membrane conductance, which underlies the unique electrical activity pattern in each of these cell types.  These processes are governed by the expression, localization and activity of voltage-gated ion channels, mainly the voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels.  In mammalian brain these processes are homeostatically regulated during development and aging, and in response to short- and long-term changes in neuronal activity in the face of sustained alterations in synaptic stimulations, which otherwise could drive the neuronal activity towards extreme excitation or quiescence.  Altered expression and/or modifications in the specific sub-cellular localization and functions of Kv channels mainly mediate such homeostatic processes in response to altered neuronal activity, seizures, ischemic stroke, neuromodulatory stimuli, brain tumor growth, and HIV-1 infection in the brain.  We are investigating distinct modifications in Kv channel function, localization and expression in mammalian brain neurons by factors/mediators released during cerebral ischemic stroke-reperfusion injury and upon exposure to HIV-1 regulatory/surface proteins, acting through specific GPCRs and growth factor receptors.  Such short-term modifications in Kv channel localization and function brings-in cellular plasticity by altering the intrinsic membrane excitability, thereby providing the neurons with a mechanism for neuroprotection.  Our study also focusses on distinct long-term modifications in Kv channel expression/localization/function that regulate neuronal survival-death dynamics in response to such pathological insults on mammalian brain.




  19. Research projects in our laboratory are/were funded by:

 
  1. National Institutes of Health (current)      Washington University Pain Center & Department of Anesthesiology (current)

  2.            

  1. American Pain Society (past)     International Association      Epilepsy Foundation (past)       US Department of Defense

  2.                                                       for the Study of Pain (past)                                                        CDMRP-PCRP (past)

  1. The University of Iowa (past)