The research in Dr. Daichao Xu’s lab investigates proteins that can regulate both cell death and inflammation. Dr. Xu’s lab is revealing how these proteins contribute to aging-related disorders, inflammatory and degenerative diseases including: premature aging, Alzheimer’s disease, non-alcohol fatty liver disease, inflammatory bowel disease, as well as pathogen infection. Cell death and inflammatory responses is important for effective host defense and injury repair. However, unwanted cell death along with chronic inflammation can cause tissue damage and is involved in the pathogenesis of a plethora of inflammatory diseases. Cell death and chronic inflammation are also implicated in aging and aging-related pathologies. Therefore, cell death and inflammation need to be tightly regulated to ensure effective host defense and injury repair while preventing excessive tissue pathology and disease. The goal of Dr. Xu’s lab is to translate these discoveries into new treatments for these scourges.

Dr. Xu’s recent studies identified TBK1, a major genetic cause for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comorbidity, as a novel regulator of cell death pathways and inflammation, and described how partial loss of function of TBK1 leads to age-dependent neurodegeneration. A more recent work of Dr. Xu identified TRADD, an adaptor protein in TNFα signaling pathway, as a direct regulator of both cellular homeostasis and cell death, and demonstrated that pharmacological targeting of TRADD may represent a promising strategy for inhibiting cell death and restoring homeostasis to treat human diseases.

Dr. Xu’s lab uses a wide array of approaches including cell biology, biochemistry, genetics and small molecules so that discoveries made at the molecular level can be transposed into physiological findings in vivo. The lab is now focus on three key families of molecules: the TNF super family that regulates inflammation and cell death; RIP kinases, which play an important role in effecting inflammation, apoptotic, necroptotic and pyroptotic cell death; autophagy-related proteins (ATG) that regulate cellular homeostasis.