Research Areas

1. How do immune cells sense, respond and adapt to tissue microenvironment, and how does such local response regulate tissue physiology or pathology?

2. How does metabolism (cellular metabolism and microbial metabolites) modulate immune function?

3. How does the peripheral immune system interact with the central nervous system?

Highlights

Dr. Wu’ postdoctoral work has made significant contributions to the study of immunology, metabolism and microenvironment: (1) the development of a novel in vivo naive T cell genetic screening system, greatly accelerating in vivo functional study of T cells; (2) the first identification of a gene that is selectively required by pathogenic but dispensable in nonpathogenic Th17 cells, addressing a critical question in the study of Th17 and autoimmunity; and (3) the insight that cellular metabolism can modulate immune cell function in a tissue microenvironment-specific manner, paving new research directions in immunometabolism (Cell, first author and co-corresponding author). In addition, Dr. Wu’s graduate work characterized molecular mechanisms by which three USH I proteins regulate the development of inner ear hair cells and how their mutations lead to deafness (Science, JBC, PNAS). His work has been recognized by a National Multiple Sclerosis Society Postdoctoral Fellowship Award, the NIH/NCI Institutional Postdoctoral Training Grant Award, the Hong Kong Young Scientist Award, and with an invitation to chair a Keystone symposium session etc.

To build upon his postdoctoral findings going forward, Dr. Wu will further investigate the relationship between microbiota, immune system and neuronal system, with the use of mouse models of autoimmune, neurodegenerative and infectious diseases. The questions being asked are 1) how do immune cells orchestrate metabolic adaptation to microenvironments, 2) how do microbial metabolites impact immune function, and 3) how do peripheral immune activities modulate CNS function? Dr. Wu hopes his work can reveal novel mechanisms of immune regulation, and ultimately improve therapeutics for these immune disorders. 

Honors

• 2021 National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas) （China)

• 2021 Oversea High-Caliber Personnel Award, Level B, ShenZhen

• 2021 NIH/NCI Institutional Training Grant Award: Molecular Oncology and Immunology Training Grant

• 2014-2017 National Multiple Sclerosis Society Postdoctoral Fellowship Award

• 2011 Hong Kong Young Scientist Award (Hong Kong Institution of Science)

• 2010 Postgraduate Achievement Award (Hong Kong University of Science and Technology)

• 2005 Excellent Graduate Student Scholarship of Sun Yat-sen University

• 2004 Kaisi Scholarship of Sun Yat-sen University

Selected Publications

1. Wu L#, Hollinshead KER, Hao Y, Au C, Kroehling L, Ng C, Lin WY, Li D, Silva HM, Shin J, Lafaille JJ, Possemato R, Pacold ME, Papagiannakopoulos TY, Kimmelman AC, Satija R, Littman DR#. Niche-selective inhibition of pathogenic Th17 cells by targeting metabolic redundancy. Cell. 2020. 182: 641-654. (# Corresponding author).

•  - Faculty opinion

•  - Nature Review Drug Discovery highlight

•  - Signal Transduction and Targeted Therapy Article Review

•  - JRNClub Video Interview

•  - BioArt Invited Talk

2. Wu L*, Pan L*, Zhang C, Zhang M. Large protein assemblies formed by multivalent interactions between cadherin23 and harmonin suggest a stable anchorage structure at the tip link of stereocilia. JBC. 2012. 287: 33460-33471 (* equal contribution)

3. Wu L*, Pan L*, Wei Z, Zhang M. Structure of MyTH4-FERM domains in myosin VIIa tail bound to cargo. Science. 2011. 331:757-760 (* equal contribution)

 - Faculty opinion 

4. Lee JY, Hall JA, Kroehling L, Wu L, Najar T, Nguyen HH, Lin WY, Yeung ST, Silver HM, Li D, Hine A, Loke P, Hudesman D, Martin JC, Kenigsberg E, Merad M, Khanna KM, Littman DR. Serum amyloid A proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell, 2020. 180: 79-91.

5. Hang S, Paik D, Devlin AS, Jamma T, Lu J, Ha S, Nelson BN, Kelly SP, Wu L, Zheng Y, Rastinejad F, Krout MR, Fischbach MA, Littman DR, Huh JR. Bile acid metabolites control Th17 and Treg cell differentiation. Nature, 2019. 576, 143–148.