B cell-depleting therapies using anti-CD20 monoclonal antibodies have been successful for the treatment of relapsing-remitting multiple sclerosis (RRMS); however, B cell-depletion showed incomplete efficacy for the treatment of autoantibody-mediated autoimmune conditions, including Systemic Lupus Erythematosus (SLE) and neuromyelitis optica (NMO), most likely because of the failure to eliminate autoantibody-producing long-lived plasma cells (PCs).

Basic Research

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.