Neural stem cell/progenitors cells give rise to mature neurons, astrocytes and oligodendrocytesthroughout life. However, neurogenesis rapidly declines during aging and the mechanism forage-dependent neural stem cell dysfunction is not clear. The ventricular-subventricular zone (V-SVZ), lining the lateral ventricle, is home to the largest pool of neural stem cells in the murinebrain. We have found that microglia, the innate immune cells of the brain, are prominentlypositioned throughout the young and aged V-SVZ niche.

Aging is the strongest known risk factor for Alzheimer's disease (AD), the most common cause ofdementia in older individuals. However, effective AD therapies remain elusive, which underscores the need tobetter understand disease etiology and its co-occurrence with advanced age. Apolipoprotein E (apoE) is amajor lipid carrier in the brain that transports cholesterol and other lipids such as sulfatide (a key component ofmyelin) between brain cells. APOE polymorphic alleles are the main genetic determinants of AD risk (e.g.,APOE4 allele is the strongest genetic risk factor for AD).

Obesity is a major risk factor for type II diabetes and metabolic syndromes. Increased understanding ofbody weight regulation may lead to effective strategies to combat obesity and diabetes. Hypothalamicneurons, including anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic Agouti-relatedpeptide (AgRP) neurons, integrate multiple metabolic cues (e.g. leptin and insulin) to provide a coordinatedcontrol of energy and glucose homeostasis.

Burn injury is a major clinical challenge. The causes of burns are vast and diverse, as are the sites of injury. Yet,the overwhelmingly majority of burn victims experience intense spontaneous pain and persistent allodynia, oftenyears after their injury. Opioids are the standard of care for post-burn pain management, but over half of burnvictims report inadequate relief, thereby increasing the risk for prolonged, and even irreversible, disability. Inaddition, opioids clearly exert dangerous side effects that include cognitive dysfunction, respiratory depression,tolerance, and dependence.