Research in Dr. Li’s laboratory focuses on the effects of pre-ischemic hyperglycemia and of acidosis on the outcome of an ischemic injury. The objective is to explore whether elevated glucose level and enhanced acidosis exacerbate ischemic brain damage by triggering mitochondrial dysfunction, activating cell death pathways, or suppressing cell survival pathways and if pharmacological intervention aiming at preserving mitochondrial function can ameliorate such enhanced ischemic brain damage.

Another research focus in Dr. Li’s laboratory is on the role of lysyl oxidase, an extracellular matrix enzyme, in angiogenesis. Angiogenesis, the formation of new vessels caused by the sprouting of endothelial cells from pre-existing vessels, occures in a wide range of pathologic processes. Pathological angiogenesis has been recognized as a hallmark of cancer progression. It also occurs in other disease conditions such as ischemic stroke and diabetic retinopathy. Manipulation of new vessel formation can be an innovative means of therapy for cancer, ischemia, and retinopathy. The objective of this project is to determine whether lysyl oxidase plays a role in mediating angiogenic processes induced by cancer and cerebral ischemia and what the underlying molecular mechanisms are for the action.

Illustration: Hyperglycemia activates caspase 3-associated cell death pathway and suppresses cAMP-responsive element-binding protein (CREB)-mediated cell survival pathways in the nuclei of the neurons subjected to transient stroke and reperfusion. NG: normoglycemia, HG: hyperglycemia, DM: diabetes, 3h and 6h: 3 and 6 hours of reperfusion.

Numbers of blood vessels and branching points are increased after transient ischemia in rats treated with lysyl oxidase inhibitor (B) compared with non-treated rat (A).