Kevin S. Lee

Education

  • BA, University of Southern California
  • PhD, University of California, Irvine

Primary Appointment

  • Professor, Neuroscience

Contact

Research Interest(s)

Neuronal Vulnerability: A Study of Cellular Mechanism

Research Description

Our laboratory is interested in the cellular mechanisms of neuronal vulnerability associated with stroke. A multidisciplinary approach has been undertaken to elucidate how neurons are destabilized during ischemia and what mechanisms underlie the degenerative process. Knowledge from these basic investigations are then utilized to develop and test specific therapeutic strategies for rescuing damaged neurons. The specific mechanisms currently under investigation in the laboratory are listed below.

1. Post-ischemic hyperexcitability; the role of adenosine. Adenosine is a potent, endogenous anti-convulsant whose neuromodulatory actions are comprised following transient ischemia. The role of attenuated neuronal inhibition in the process neuronal death is being examined in selectively vulnerable hippocampal neurons.

2. The role of calpain in ischemic cell death. The elevation of intracellular calcium concentrations plays a critical role in cellular damage in a variety of disease states. These studies are examining the role of calcium-activated, intracellular proteases in the cell death process.

3. Effects of calpain inhibitors on focal cerebral ischemia. Activation of the protease, calpain has been implicated in the process of ischemic neuronal death. Newly-developed inhibitors of calpain are being tested for their potential neuroprotective influence in a model of reversible, focal ischemica.

4. Cerebrovascular effects of novel peptides in cerebral vasospasm. Protein kinase C and calponin are important regulators of vascular contractility and are preferred substrates for calcium-activated proteolysis are being studies in models of cerebral vasospasm to determine their influence on pathological vascular constriction.

5. Neurovascular communication in the CNS. The manner in which microvascular tone is couple to neuronal activity in the parenchyma of the CNS is under investigation. The roles of excitatory and inhibitory transmitters in signaling microvessels are being clarified.

6. Development of the mammalian neocortex. Neuocortical development is being investigated in a novel mutant rat which exhibits a double cortex. This type of neocortical malformation may underlie certain forms of epilepsy.

This research is funded by the National Institutes of Health, the National Science Foundation, the Upjohn Company, Cortex Pharmaceuticals, Chugai Pharmaceuticals, Ciba Geigy, and Elekta Instruments.

Selected Publications

  • Wang Y, Yoshimura R, Manabe H, Schretter C, Clarke R, Cai Y, Fitzgerald M, Lee K. Trans-sodium crocetinate improves outcomes in rodent models of occlusive and hemorrhagic stroke. Brain research. 2014;1583 245-54. PMID: 25128603 | PMCID: PMC4170841
  • Manabe H, Wang Y, Yoshimura R, Cai Y, Fitzgerald M, Clarke R, Lee K. Metabolic reflow as a therapy for ischemic brain injury. Acta neurochirurgica. Supplement. 2010;110 87-91. PMID: 21125451
  • Manabe H, Okonkwo D, Gainer J, Clarke R, Lee K. Protection against focal ischemic injury to the brain by trans-sodium crocetinate. Laboratory investigation. Journal of neurosurgery. 2009;113(4): 802-9. PMID: 19961314 | PMCID: PMC3380430
  • Lin C, Shih H, Lieu A, Lee K, Dumont A, Kassell N, Howng S, Kwan A. Attenuation of experimental subarachnoid hemorrhage--induced cerebral vasospasm by the adenosine A2A receptor agonist CGS 21680. Journal of neurosurgery. 2007;106(3): 436-41. PMID: 17367066
  • Lin C, Dumont A, Calisaneller T, Kwan A, Hwong S, Lee K. Monoclonal antibody against E selectin attenuates subarachnoid hemorrhage-induced cerebral vasospasm. Surgical neurology. 2005;64(3): 201-5; discussion 205-6. PMID: 16099244
  • Yunoki M, Nishio S, Ukita N, Anzivino M, Lee K. Hypothermic preconditioning induces rapid tolerance to focal ischemic injury in the rat. Experimental neurology. 2003;181(2): 291-300. PMID: 12782001