Joseph LaManna

Professor

Ph.D. Duke University, 1975
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Protein Structures and Interaction Dynamics in Neuronal Cell Signaling

RESEARCH DESCRIPTION

The laboratory continues to pursue the physiological mechanisms that link neuronal activity to brain blood flow and metabolism. These mechanism involve the interaction of neurons, glia and capillary endothelium as a neurovascular unit. Neurovascular units display plasticity in response to environmental challenges such as adaptation to the chronic hypoxia of altitude, and are damaged by pathological insults such as cerebral ischemia. Transporters of substrates through the blood brain barrier include both GLUT-1 (glucose) and MCT-1 (ketones).

Adaptation to chronic hypoxia involves HIF-1 and COX-2 mediated angiogenesis. The HIF-1 pathway involves upregulation of over 40 genes, including those of glycolysis, EPO, GLUT-1, and VEGF. The COX-2 pathway includes PGE2 dependent upregulation of angiopoietin-2.

Significant post recovery morbidity and mortality from cardiac arrest is due to central nervous system failure. The deleterious effect are increased with increasing age. Neuroprotection mechanisms including pre-conditioning can help by activating oxidative stress response mechanisms controlled by transcription factors such as HIF-1. IGF-1 and inhibitors of prolyl hroxylase can be used to increase HIF-1 accumulation and improve recovery from global and focal cerebral ischemia.

RELATED RESEARCH AREAS

View Joseph LaManna's Publications on PubMed