Lanbo Shi, Ph.D.
Assistant Professor of Medicine
shila@njms.rutgers.edu |
Office: Room W310P Phone: +(1)973-854-3320
Lab: Room W310Q Phone: +(1)973-854-3322
Immunometabolism and host-directed therapy in tuberculosis
Despite extensive efforts over three decades, tuberculosis (TB) remains a significant infectious disease. In 2022, 7.5 million new TB cases were reported, the highest number since global TB monitoring began in 1995. The challenge is further compounded by drug-resistant strains of Mycobacterium tuberculosis (Mtb), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) variants, necessitating prolonged multidrug treatment for a successful cure. The recent COVID-19 pandemic has exacerbated these issues, leading to disruptions in TB care and an estimated half a million excess TB deaths from 2020 to 2021. These statistics underscore the urgent need for innovative strategies in TB prevention and control.
One promising approach is the development of adjunct host-directed therapies (HDTs) that target host immune cells to enhance the clearance of the tubercle bacilli without causing antimicrobial resistance. Dr. Shi’s laboratory focuses on immunometabolism in TB, an emerging field that explores the relationship between the metabolic pathways of host immune cells and their specific immune functions. Recent advancements have highlighted the pivotal role of metabolic reprogramming in host immune cells for proinflammatory and antimicrobial responses during mycobacterial infection. Key changes include the induction of hypoxia-inducible factor 1 alpha (HIF-1α), increased glucose uptake, and enhanced glycolysis, reminiscent of the Warburg effect observed in cancer cells. Additionally, metabolic remodeling of amino acid metabolism and the emerging role of mitochondria in generating and releasing biosynthetic precursors and signaling molecules underscore the complex metabolic remodeling programs of host immune cells in response to mycobacterial infection. Increasing evidence indicates that the pathogen modulates the metabolic reprogramming of host immune cells as a mechanism of pathogenicity.
Using multiple approaches such as metabolomics (including tracing metabolomics), transcriptomics, single molecule RNA-FISH, FACS, immunofluorescence imaging, pharmacological intervention, nutrient supplementation, and both whole-body and conditional knockout mouse strains, Dr. Shi’s group is dissecting the metabolic determinants of immune cell functions associated with different infection outcomes. Insights into host immunometabolism in TB are anticipated to pave the way for developing HDTs that enhance the antimicrobial functions of immune cells by tailoring their metabolism. Research projects in Dr. Shi’s lab are funded by the National Institutes of Health (NIH).
Kumar R, Kolloli A, Subbian S, Kaushal D, Shi L, Tyagi S (2024) Imaging the Architecture of Granulomas Induced by Mycobacterium tuberculosis Infection with Single-molecule Fluorescence In Situ Hybridization. J Immunol. PMI: 38912840
Jiang Q, Qiu Y, Kurland IJ, Drlica K, Subbian S, Tyagi S, Shi L (2022) Glutamine Is Required for M1-like Polarization of Macrophages in Response to Mycobacterium tuberculosis Infection. mBio 13: e0127422. PMI: 35762591
Jiang Q, Linn T, Drlica K, Shi L (2022) Diabetes as a potential compounding factor in COVID-19-mediated male subfertility. Cell Biosci 12: 35. PMI: 35307018
Ma MT, Badeti S, Chen CH, Kim J, Choudhary A, Honnen B, Reichman C, Calianese D, Pinter A, Jiang Q, Shi L, Zhou R, Xu H, Li Q, Gause W, Liu D (2021) CAR-NK Cells Effectively Target SARS-CoV-2-Spike-Expressing Cell Lines In Vitro. Front Immunol 12: 652223. PMI: 34367128
Jiang Q, Shi L (2021) Coordination of the Uptake and Metabolism of Amino Acids in Mycobacterium tuberculosis-Infected Macrophages. Frontiers in Immunology 12.
Jiang Q, Maresch CC, Petry SF, Paradowska-Dogan A, Bhushan S, Chang Y, Wrenzycki C, Schuppe HC, Houska P, Hartmann MF, Wudy SA, Shi L, Linn T (2020) Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome. JCI Insight 5. PMI: 33148888
Kumar R, Singh P, Kolloli A, Shi L, Bushkin Y, Tyagi S, Subbian S (2019) Immunometabolism of Phagocytes During Mycobacterium tuberculosis Infection. Frontiers in Molecular Biosciences 6
Shi L, Jiang Q, Bushkin Y, Subbian S, Tyagi S (2019) Biphasic Dynamics of Macrophage Immunometabolism during Mycobacterium tuberculosis Infection. MBio 10. PMI: 30914513
Shi L, Eugenin EA, Subbian S (2016) Immunometabolism in Tuberculosis. Front Immunol 7: 150. PMI: 27148269
Giffin MM, Shi L, Gennaro ML, Sohaskey CD (2016) Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence. PLoS One 11: e0155522. PMI: 27203084
Du P, Sohaskey CD, Shi L (2016) Transcriptional and Physiological Changes during Mycobacterium tuberculosis Reactivation from Non-replicating Persistence. Front Microbiol 7: 1346. PMI: 27630619
Shi L, Salamon H, Eugenin EA, Pine R, Cooper A, Gennaro ML (2015) Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Sci Rep 5: 18176. PMI: 26658723
Salamon H, Bruiners N, Lakehal K, Shi L, Ravi J, Yamaguchi KD, Pine R, Gennaro ML (2014) Cutting edge: Vitamin D regulates lipid metabolism in Mycobacterium tuberculosis infection. J Immunol 193: 30-34. PMI: 24899504
Datta P, Shi L, Bibi N, Balazsi G, Gennaro ML (2011) Regulation of central metabolism genes of i by parallel feed-forward loops controlled by sigma factor E (sigma(E)). J Bacteriol 193: 1154-1160. PMI: 21193605
Shi L, Sohaskey CD, Pfeiffer C, Datta P, Parks M, McFadden J, North RJ, Gennaro ML (2010) Carbon flux rerouting during Mycobacterium tuberculosis growth arrest. Mol Microbiol 78: 1199-1215. PMI: 21091505
Hussain S, Malik M, Shi L, Gennaro ML, Drlica K (2009) In vitro model of mycobacterial growth arrest using nitric oxide with limited air. Antimicrob Agents Chemother 53: 157-161. PMI: 18955516
Shi L, Sohaskey CD, North RJ, Gennaro ML (2008) Transcriptional characterization of the antioxidant response of Mycobacterium tuberculosis in vivo and during adaptation to hypoxia in vitro. Tuberculosis (Edinb) 88: 1-6. PMI: 17928268
Balazsi G, Heath AP, Shi L, Gennaro ML (2008) The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol Syst Biol 4: 225. PMI: 18985025
Shi L, Sohaskey CD, Kana BD, Dawes S, North RJ, Mizrahi V, Gennaro ML (2005) Changes in energy metabolism of Mycobacterium tuberculosis in mouse lung and under in vitro conditions affecting aerobic respiration. Proc Natl Acad Sci U S A 102: 15629-15634. PMI: 16227431
Davidow A, Kanaujia GV, Shi L, Kaviar J, Guo X, Sung N, Kaplan G, Menzies D, Gennaro ML (2005) Antibody profiles characteristic of Mycobacterium tuberculosis infection state. Infect Immun 73: 6846-6851. PMI: 16177363
Shi L, North R, Gennaro ML (2004) Effect of growth state on transcription levels of genes encoding major secreted antigens of Mycobacterium tuberculosis in the mouse lung. Infect Immun 72: 2420-2424. PMI: 15039373
Shi L, Jung YJ, Tyagi S, Gennaro ML, North RJ (2003) Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence. Proc Natl Acad Sci U S A 100: 241-246. PMI: 12506197