Public Health Research Institute Center and
at the International Center for Public Health
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103, USA
Phone: (973) 854-3322
Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis, is the second most deadly disease from a single infectious agent. The major cause of morbidity and mortality from TB results predominantly from reactivation of an established latent infection. TB results from complex bacterium-host interactions and its pathologic hallmark is the formation of granulomas. A granulomatous lesion is a compact, dynamic and organized structure of immune cell aggregates, and it comprises a central area of M. tuberculosis-infected cells surrounded by other noninfected phagocytic cells and lymphocytes at the periphery. While granuloma is able to localize and contain M. tuberculosis by concentrating the immune response, recent studies indicate that M. tuberculosis has evolved with the ability not only to adapt to the hostile environment in granulomas but also to cause host pathology that ultimately allows the infection to progress and disseminate. Thus, M. tberculosis-containing granulomas represent a dynamic balance between the host antibacterial effector mechanisms and the bacterial pathogenicity. One aspect of Dr. Shi’s research is focused on the elucidation of mechanisms of bacterial physiological and metabolic transformation during disease progression and during reactivation. Recent study of the physiological changes and molecular events in the lag phase of M. tuberculosis reactivation reveals the upregulation of specific metabolic pathways and regulatory networks that play important roles for M. tuberculosis to prepare for logarithmic growth.
The other aspect of Dr. Shi’s research is focused on study of the interrelationship between the bioenergetic pathways of host immune cells and their specific immune functions. Recent research findings indicate that host immune cells switch to utilize aerobic glycolysis as a carbon and energy source in response to M. tuberculosis infection, and this metabolic switch is associated with the induction of the Hypoxia Inducible Factor 1 (HIF-1), a master transcription regulator of genes involved in energy metabolism. This change of energy strategy in host immune cells is analogous to Warburg effect, the metabolic state of cancer cells. Increasing evidence indicates that occurrence of Warburg effect in immune cells through HIF-1 activation is an important mechanism of host antibacterial and inflammatory response to M. tuberculosis infection, and that the pathogen hijacks Warburg effect as a mechanism of pathogenesis. Studying the links between Warburg effect and antibacterial functions and inflammatory response could thus lead to the development of immunotherapy to enhance antibacterial functions by manipulating the metabolism of immune cells. This host-targeted strategy would help treat/cure the drug-resistant TB.
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
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
Shi L, Eugenin EA, Subbian S (2016) Immunometabolism in Tuberculosis. Front Immunol 7: 150. PMI: 27148269
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 Mycobacterium tuberculosis 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
Singh A, Singh Y, Pine R, Shi L, Chandra R, Drlica K (2006) Protein kinase I of Mycobacterium tuberculosis: cellular localization and expression during infection of macrophage-like cells. Tuberculosis (Edinb) 86: 28-33. PMI: 16256441
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
Shi L, Guttenberger M, Kottke I, Hampp R (2002) The effect of drought on mycorrhizas of beech (Fagus sylvatica L.): changes in community structure, and the content of carbohydrates and nitrogen storage bodies of the fungi. Mycorrhiza 12: 303-311. PMI: 12466918
Lowe A, Einig W, Shi L, Hampp R (2000) Mycorrhiza Formation and Elevated CO2 Both Increase the Capacity for Sucrose Synthesis in Source Leaves of Spruce and Aspen. New Phytologist 145: 565-574. PMI: 0
Wiese C, Shi L, Heber U (1998) Oxygen Reduction in the Mealer Reaction Is Insufficient to Protect Photosystems I and II of Leaves against Photoinactivation. Physiologia Plantarum 102: 437-446. PMI: 0
Ph.D. 2000 (Mycology and Plant Physiology): University of Tuebingen, Tuebingen, Germany.
Visiting Research Scientist, 1996: Institute of Botany, University of Wuerzburg, Wuerzburg Germany;
Postdoctoral Fellow, 2000 – 2002: Public Health Research Institute, New York;
Research Associate, 2002 – 2007: Public Health Research Institute, New Jersey;
Assistant Professor of Medicine, 2007 – Present: Public Health Research Institute, New Jersey Medical School, Rutgers University.