Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.

Postdoctoral Fellow, Harvard University, 2016-2019

Ph.D., Shanghai institute of Organic Chemistry, Chinese Academy of Sciences, 2011-2016

B.S., Zhejiang University, 2007-2011

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.

Significant Works

1. Xu D#, Jin T#, Zhu H, Chen H, Ofengeim D, Zou C, Mifflin L, Pan L, Amin P, Li W, Shan B, Naito MG, Meng H, Li Y, Pan H, Aron L, Adiconis X, Levin JZ, Yankner BA, Yuan J*. TBK1 Suppresses RIPK1- Driven Apoptosis and Inflammation during Development and in Aging. Cell. 2018. 174(6):1477-1491. PMID: 30146158.

2. Xu D#, Zhao H#, Jin M, Zhu H, Shan B, Geng J, Dziedzic SA, Amin P, Mifflin L, Naito MG, Najafov A, Xing J, Yan L, Liu J, Qin Y, Hu X, Wang H, Zhang M, Manuel VJ, Tan L, He Z, Sun ZJ, Lee VMY, Wagner G, Yuan J*. Modulating TRADD to restore cellular homeostasis and inhibit apoptosis. Nature. 2020. 587(7832):133-138. PMID: 32968279.

3. Xu D#, Liu J#, Fu T, Shan B, Qian L, Pan L*, Yuan J*. USP25 regulates Wnt signaling by controlling the stability of tankyrases. Genes & Development 2017, 31 (10), 1024-1035. PMID: 28619731.

4. Xu D, Shan B, Sun H, Xiao J, Zhu K, Xie X, Li X, Liang W, Lu X, Qian L, Yuan J*. USP14 regulates autophagy by suppressing K63 ubiquitination of Beclin 1. Genes & Development 2016, 30(15), 1718-1730. PMID: 27542828.

5. Xu D, Shan B, Lee BH, Zhu K, Zhang T, Sun H, Liu M, Shi L, Liang W, Qian L, Xiao J, Wang L, Pan L, Finley D, Yuan J*. Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system. eLife 2015,4, e10510. PMID: 26523394.

6. Xu D, Zhang T, Xiao J, Zhu K, Wei R, Wu Z, Meng H, Li Y, Yuan J*. Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon. Autophagy 2015, 11 (4),617-628. PMID: 25906440.