Eng H. Lo, Ph.D.

Professor of Radiology

Massachusetts General Hospital
Room 2401
149 13th Street
Charlestown, MA 02129
Telephone: 617-726-4043
Fax: 617- 726-7830
Email: Lo@helix.mgh.harvard.edu
Predocs: 1 Postdocs: 8 Completed PhD's: 3

The MGH Neuroprotection Research Lab uses a multi-disciplinary approach in in vitro and in vivo models to investigate the molecular mechanisms that underlie cell death after stroke and trauma, and assess novel strategies for neuroprotection. Our overall working hypothesis states that after brain injury, extracellular perturbations are transduced into intracellular dysfunction via highly conserved signaling pathways. Initially, upregulation in plasminogen and matrix metalloproteinase genes mediate the disruption of critical matrix components responsible for neurovascular homeostasis. These extracellular perturbations are then transduced via mitogen activated protein (MAP) kinase signal transduction cascades into the cell. Once the "death signal" is inside, intracellular proteolysis is triggered involving among others, the caspase and calpain family of enzymes. Focussing only on intra-neuronal events is not enough. The key is to dissect the cell-cell and cell-matrix signaling within the entire neurovascular unit (neurons, astrocytes, endothelium) that forms the basis for function and dysfunction.

References:

• Lo EH, Dalkara TD, Moskowitz MA. Emerging mechanisms, challenges, and opportunities in stroke. Nature Rev Neurosci 2003; 4:399-415.
• Wang X, Lee S, Arai K, Tsuji K, Lee SR, Rebeck GW, Lo EH. Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nature Med 2003; 9:1313-1317.
• Lee SR, Tsuji K, Lee S, Lo EH. Role of matrix metalloproteinase in delayed neuronal damage after transient global cerebral ischemia. J Neurosci 2004; 24:671-678.
• Lo EH, Moskowitz MA, Jacobs TP. Exciting, radical, suicidal: how brain cells die after stroke? Stroke 2005; 36:189-192.
• Lee SR, Kim HY, Rogowska J, Zhao BQ, Bhide P, Parent JM, Lo EH. Involvement of matrix metalloproteinase in neuroblast cell migration from subventricular zone after stroke. J Neurosci 2006 (in press).
• Zhao BQ, Wang S, Kim HY, Storrie H, Rosen BR, Mooney DJ, Wang X, Lo EH. ROle of matrix metalloproteinase in delayed cortical responses after stroke. Nature Med 2006 (in press).