Haoxing Xu received his undergraduate degree from Peking University, Ph.D from Georgia State University, and postdoctoral training with David Clapham at Children's Hospital Boston.  He then joined the University of Michigan in 2007 where he is a professor at the Department of Molecular, Cellular and Developmental Biology.  He is currently a Chair Professor at Liangzhu Laboratory & Zhejiang University Medical Center, and Dean of School of Basic Medical Sciences, Zhejiang University.   Dr. Xu has received multiple faculty awards including the Sloan Fellowship (Alfred P. Sloan Foundation), the Presidential Early Career Award for Sciences and Engineers (White House), and Henry Russel Award and Faculty Recognition Award (University of Michigan).  Dr. Xu co-founded Gordon Research Conference (GRC) on “Organellar Channels and Transporters” (inaugural meeting in Boston, 2015), and China Lysosome Conference (inaugural meeting in Hangzhou, 2023).

More than 50 human diseases collectively called lysosome storage diseases (LSDs) are the result of problems in trafficking to, degradation within, or export from lysosomes. Emerging evidence suggests that common neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are also lysosomal (dysfunction) disorders.  In response to cellular cues in the endocytic and autophagic pathways, lysosomes use H+ flux to establish the working environment for hydrolases, H+, Na+, K+, and Cl- fluxes to establish the lysosomal membrane potential essential for driving catabolite export, and Ca2+ and H+ channels to carry the signals needed for precise delivery of cargo and hydrolases, as well as timely removal of catabolites. 

Dr. Xu has developed a unique research program for understanding the cell biology of lysosomes, and its relationship to lysosomal storage disorders and common neurodegenerative diseases such as AD and PD. This program combines electrophysiological and imaging approaches typically used to study plasma membrane ion channels with molecular and biochemical approaches typically used to understand organelle function. The combined approach has allowed his lab to find eight lysosomal ion channels (Ca2+, Na+, K+, Fe2+/Zn2+, Cl-, and H+) and identify the activating cellular cue for each of them. With his unique and combined expertise in both organellar electrophysiology and chemical cell biology, Dr. Xu’s work may not only reveal at the molecular level how information exchange occurs rapidly between the lysosomal lumen and cytosol, but also lead to new therapeutic approaches to treating lysosomal diseases.

Dr. Xu’s major achievements concern the discovery of key cell biological roles for several of these lysosomal ion channels.

• New patch-clamp methods were developed to directly study channels in endolysosomes. His group demonstrated that TRPMLs are the principle Ca2+ release channels of lysosomes.

• New imaging methods to detect lysosomal Ca2+ release, lysosomal H+ release, phosphoinositide dynamics, and lysosomal membrane potential changes were developed. Dr. Xu identified key roles of TRPMLs in regulating lysosomal exocytosis, phagocytosis, membrane repair, gastric acid secretion, and lysosome transport and biogenesis.

• Dr. Xu’s group identified TPCs as Na+-selective channels and LysoKVCa as K+-selective channels that regulate lysosomal membrane potential, revealing a new dimension in the regulation of endosomes and lysosomes.

• Xu discovered Parkinson's Disease risk protein TMEM175 as the long-sought proton “leak” channel of lysosomes and endosomes that regulates lysosome pH set-point, optimum, and homeostasis.

• Xu discovered ER-lysosome membrane contact as the primary mechanism that regulates lysosome Ca2+ store refilling.

• Dr. Xu discovered LRRC8A as the key player that regulate osmo- homeostasis in the lysosome.

• Dr. Xu’s group has collectively found that TRPML1 inhibition may be a primary pathogenic mechanism causing many different LSDs.

• Xu demonstrated that small-molecule TRPML agonists can speed lysosomal trafficking, reduce lysosome storage and increase membrane repair, providing novel approaches for the treatment of LSDs and Muscular Dystrophies.