Dr. Jim Sun

Biography

Research Interests

The Sun laboratory is focused on understanding host immunity to Mycobacterium tuberculosis (Mtb) and other bacterial infections. Infection with Mtb causes tuberculosis (TB), which remains the leading cause of infectious diseases related deaths worldwide due to a single bacterial pathogen. Multi-drug resistant TB (MDR-TB) is also the single largest disease component of the global antimicrobial resistance crisis, a pandemic lurking in the shadows that is predicted to cause 10 million death per year by 2050.

Our goal is to develop novel host-directed therapies for TB and other bacterial infections. Targeting and harnessing the power of our own immune cells to kill invading pathogens offers unique promise to overcome the development of antibiotic resistance.

My research program has two major objectives:

• knowledge generation:identify physiologically relevant new host and/or bacterial targets suitable for drug development using a multidisciplinary approach
• drug discovery: promising host and/or bacterial targets are then put through a drug discovery pipeline that aims to develop lead compounds

Using this approach, my lab has identified and characterized several promising host targets and discovered lead compounds with in vitro and in vivo efficacy. My long-term vision is that our work will apply not only to TB research but also therapy for intracellular bacterial pathogens.

For more information about specific research projects, please visit the Sun Lab website.

Selected Publications

Full publication list

Google scholar

• Berton S, Chen L, Liang YC, Xu Z, Afriyie-Asante A, Rajabalee N, Yang W, Sun J. A selective PPM1A inhibitor activates autophagy to restrict the survival of Mycobacterium tuberculosis. Cell Chem Biol. 2022;S2451-9456(22)00094-0. doi: 10.1016/j.chembiol.2022.03.006.
• Madden K, Liang YC, Rajabalee N, Alvarez GG, Sun J. Surveying the Epigenetic Landscape of Tuberculosis in Alveolar Macrophages. Infect Immun. 2022;e0052221. doi: 10.1128/iai.00522-21.
• Afriyie-Asante A, Dabla A, Dagenais A, Berton S, Smyth R, Sun J. Mycobacterium tuberculosis Exploits Focal Adhesion Kinase to Induce Necrotic Cell Death and Inhibit Reactive Oxygen Species Production. Front Immunol. 2021;12:742370. doi: 10.3389/fimmu.2021.742370.
• Smyth R, Sun J. Protein Kinase R in Bacterial Infections: Friend or Foe? Front Immunol. 2021;12:702142. doi: 10.3389/fimmu.2021.702142.
• Smyth R, Berton S, Rajabalee N, Chan T, Sun J. Protein Kinase R Restricts the Intracellular Survival of Mycobacterium tuberculosis by Promoting Selective Autophagy. Front Microbiol. 2021;11:613963. doi: 10.3389/fmicb.2020.613963.
• Pajuelo D, Gonzalez-Juarbe N, Tak U, Sun J, Orihuela CJ, Niederweis M. NAD⁺ Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosis. Cell Rep. 2018;24(2):429-440. doi: 10.1016/j.celrep.2018.06.042.
• Smith SR, Schaaf K, Rajabalee N, Wagner F, Duverger A, Kutsch O, Sun J. The phosphatase PPM1A controls monocyte-to-macrophage differentiation. Sci Rep. 2018;8(1):902. doi: 10.1038/s41598-017-18832-7.
• Schaaf K, Smith SR, Duverger A, Wagner F, Wolschendorf F, Westfall AO, Kutsch O, Sun J. Mycobacterium tuberculosis exploits the PPM1A signaling pathway to block host macrophage apoptosis. Sci Rep. 2017;7:42101. doi: 10.1038/srep42101.
• Sun J*, Schaaf K, Duverger A, Wolschendorf F, Speer A, Wagner F, Niederweis M and Kutsch O. (2016) Protein Phosphatase, Mg²⁺/Mn²⁺-dependent 1A controls the innate antiviral and antibacterial response of macrophages during HIV-1 and Mycobacterium tuberculosis infection. Oncotarget, 7(13):15394-15409. *co-corresponding author
• Sun J, Siroy A, Lokareddy RK, Speer A, Doornbos KS, Cingolani G, Niederweis M. (2015) The Tuberculosis Necrotizing Toxin kills macrophages by hydrolyzing NAD⁺. Nat Struct Mol Biol, 22(9):672-8. doi: 10.1038/nsmb.3064.
• Danilchanka O, Sun J, Pavlenok M, Maueröder C, Speer A, Siroy A, Marrero J, Trujillo C, Mayhew DL, Doornbos KS, Muñoz LE, Herrmann M, Ehrt S, Berens C, Niederweis M. (2014) An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity. Proc Natl Acad Sci U S A, 6;111(18):6750-5.
• Sun J, Singh V, Lau A, Stokes RW, Obregón-Henao A, Orme IM, Wong D, Av-Gay Y, Hmama Z. (2013) Mycobacterium tuberculosis nucleoside diphosphate kinase inactivates small GTPases leading to evasion of innate immunity. PLoS Pathog, 9(7):e1003499.
• Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y. (2011) Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A, 108(48):19371-6.