Pak H. Chan

Title
Professor

Department
Neurosurgery

Research Interests
Molecular and cellular mechanisms of cell death in CNS injury and in neurodegeneration using transgenic and knockout strategies.

Email
phchan@stanford.edu

Phone
498-4457

Fax
498-4550

Address
1201 Welch Road MSLS #P314
Mail Code: 5487

Faculty Research Description
My primary research interest is to understand the molecular and cellular mechanisms of cell death in the CNS following acute injuries such as ischemia and trauma and chronic neurodegenerative diseases such as Parkinson disease. We will focus on the role of oxidative stress, mitochondrial dysfunction, DNA damage and repair, various gene expressions (gene family of HSP72, Bcl-2, c-fos and COX-2) and various transcription factors (NFkB, AP1, etc.) in the pathogenesis of necrosis and/or apoptosis. Various transgenic and knockout mutant mice of CuZn-superoxide dismutase (SOD1) and mitochondrial manganese SOD (SOD2) have been generated to address the role of superoxide radicals in these cell death processes. In addition, human SOD1 transgenic rats have been established as a model for the study of oxidative mechanisms and acute and chronic CNS injuries. The long-term goal of our research is to derive therapeutic strategies at the cellular and molecular level to ameliorate cell death in CNS injuries.

Chan PH, Kawase M, Murakami K, Chen SF, Li Y, Calagui B, Reola L, Carlson E, Epstein CJ. (1998). Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion. J Neurosci 18:8292-8299.

Fujimura M, Morita-Fujimura Y, Kawase M, Copin, J-C, Calagui B, Epstein CJ, Chan PH. (1999). Managanese superoxide dismutase mediates the early release of mitochondrial cytochrome c and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice. J Neurosci 19:3414-3422.

Gasche Y, Fujimura M, Morita-Fujimura Y, Copin J-C, Kawase M, Massengale J, Chan PH. (1999). Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: A possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 19:1020-1028.

Sugawara T, Fujimura M, Morita-Fujimura Y, Kawase M, Chan, PH. (1999). Mitochondrial release of cytochrome c corresponds to the selective vunerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia. J Neurosci 19:RC39, 1-6.

Manley GT, Fujimura M, Noshita N, Ma T, Filiz F, Bollen A, Chan PH, Verkman AS. (2000). Aquaporin-4 deletion in mice reduces brain edema following acute water intoxication and ischemic stroke. Nature Medicine 6:159-163.

Areas of Study
Cellular Neurobiology
Molecular Neurobiology
SBRC
Ph.D.