The Man Group - Innate Immunity and Inflammasomes

Our lab investigates the role of inflammation in infectious diseases and cancer. Pattern-recognition receptors are innate immune sensors which detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). These receptors activate signalling pathways and mediate the production of inflammatory cytokines, type I interferons and other anti-microbial molecules. We study the mechanisms by which host sensors recognise bacteria, viruses and parasites, and explore how these sensors shape the overall immune response to infection.

We investigate the role of disease-fighting immune proteins in destroying multidrug resistant pathogens. We also study how uncontrolled inflammation can be targeted by immunotherapies to prevent the development of cancer, autoimmunity and infectious diseases.

We welcome applications from undergraduate, Honours and PhD students, and research assistants and Postdoctoral fellows. E-mail the Group Leader Professor Si Ming Man (siming.man@anu.edu.au) for further information regarding project details and position availability.

Leader

Researchers

Technicians

Students

Visitors

External members

  • Kyra Ramchandani (ANU Medical School)

SELECTED PUBLICATIONS

Man, S.M*., Karki, R*., Sasai, M., Place,D.E., Kesavardhana, S., Temirov, J., Frase, S., Zhu, Q., Malireddi, R.K.S., Kuriakose, T., Peters, J.L., Neale, G., Brown, S.A., Yamamoto, M., Kanneganti, T.D. (2016) IRGB10 liberates bacterial ligands for sensing by the AIM2 and caspase-11–NLRP3 inflammasomes. Cell. 167:382–396.*Co-first author.

  • Featured in Developmental Cell: Previews: Hoss, F. Budden, C. and Latz, E. (2016) IRGB10 exposes bacteria’s intimate secrets. Developmental Cell. 39:7–8.
  • Recommended by Faculty of 1000 (F1000).

Man, S.M*., Zhu, Q*., Zhu, L*., Liu, Z*., Karki, R., Malik, A., Sharma, D., Li, L., Malireddi, R.K.S., Gurung, P., Neale, G., Olsen, S.R., Carter, R.A., McGoldrick, D.J., Wu, G., Finkelstein, D., Vogel, P., Gilbertson, R.J., Kanneganti, T.D. (2015) Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell. 162:45-58. *Co-first author.

  • Featured in Cell: Previews: Rommereim, L.M., Subramanian, N. (2015) AIMing 2 curtail cancer. Cell. 162:18-20.
  • Featured in Science Signaling: Editor’s Choice – Our AIM is 2 prevent cancer (2015) Science Signaling. 8:EC234.
  • Featured in Cancer Discovery: Research Watch: AIM2 inhibits intestinal stem cell proliferation in colorectal cancer (2015) Cancer Discovery. 5(8)

Karki, R*., Man, S.M*., Malireddi, R.K.S., Kesavardhana, S., Zhu, Q., Burton, A.R., Sharma, B.R., Pelletier, S., Vogel, P., Rosenstiel, P., Kanneganti, T.D. (2016) NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer. Nature. 540:583–587. *Co-first author.

  • Featured in Nature Reviews Immunology: Research Highlights: Leavy, O. (2017) Tumour immunology: NLRC3 inhibits mTOR in colorectal cancer. Nature Reviews Immunology. doi: 10.1038/nri.2016.152.
  • Featured in Nature Reviews Gastroenterology & Hepatology: News & Views: Gao, T., Evers, B.M. (2017) A new innate immune sensor – functions from inside the colonic epithelium. Nature Reviews Gastroenterology & Hepatology. doi:10.1038/nrgastro.2017.10
  • Featured in Science Signaling: Papers of note in Nature: Gough, N.R. (2017) NLRC3 blocks PI3K signaling. Science Signaling. 10(460).
  • Featured in Cancer Discovery: Research Watch: The Cytoplasmic Sensor NLRC3 Inhibits mTOR Signaling in Tumors. (2017) Cancer Discovery DOI: 10.1158/2159-8290.CD-RW2017-001.

Man, S.M., Karki, R., Malireddi, R.K.S., Neale, G., Vogel, P., Yamamoto, M., Lamkanfi, M., Kanneganti, T.D. (2015) The transcription factor IRF1 and guanylate-binding proteins target AIM2 inflammasome activation by Francisella infection. Nature Immunology. 16:467–475.

  • Featured in Nature Immunology: News & Views: Fitzgerald, K.A. Rathinam, V.A.K. (2015) GBPs take AIM at Francisella. Nature Immunology. 16:443–444.

Jing, W., Lo Pilato, J., Kay, C., Feng, S., Enosi Tuipulotu, D., Mathur, A., Shen, C., Ngo, C., Zhao, A., Miosge, L.A., Ali, S.A., Gardiner, E.E., Awad, M.M., Lyras, D., Robertson, A.A.B., Kaakoush, N.O., Man, S.M‡. (2022) Clostridium septicum alpha-toxin activates the NLRP3 inflammasome by engaging GPI-anchored proteins. Science Immunology. 7:eabm1803. ‡ Senior author.

  • Altmetric Score: 556.

Mathur, A., Feng, S., Hayward, J.A., Ngo, C., Fox, D., Atmosukarto, I.I.,Price, J.D., Schauer, K., Märtlbauer E., Robertson, A.A.B., Burgio, G., Fox, E.M., Leppla, S.H., Kaakoush, N.O., Man, S.M‡.(2019) A multi-component toxin from Bacillus cereus incites inflammation and shapes host outcome via the NLRP3 inflammasome. Nature Microbiology. 4:362–374. ‡ Senior author.

  • Covered by Channel Nine 6pm News, ABC News, ABC Radio and Online media.
  • Altmetric Score: 135.

Feng, S.,* Enosi Tuipulotu, D.,* Pandey, A., Jing, W., Shen, C., Ngo, C., Tessema, M.B., Li, F-J., Fox, D., Mathur, A.,Zhao, A., Runli Wang1, Pfeffer, K., Degrandi, D., Yamamoto, M., Reading, P.C., Burgio, G., Man, S.M‡.(2022) Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling. Nature Communications. 13:4395. *Co-first author. ‡ Senior author.

Fox, D*., Mathur, A*., Xue, Y., Liu, Y., Tan, W.H., Feng, S., Pandey, A., Ngo, C., Hayward, J.A., Atmosukarto, I.I.,Price, J.D., Johnson, M.D., Jessberger, N., Robertson, A.A.B., Burgio, G., Tscharke, D.C., Fox, E.M., Leyton, D.L., Kaakoush, N.O.,Märtlbauer E., Leppla, S.H., Man, S.M‡. (2020) Bacillus cereus non-Haemolytic enteroxin activates the NLRP3 inflammasome. Nature Communications. 11:760. *Co-first author. ‡ Senior author.

Man, S.M., Hopkins, L.J., Nugent, E., Cox, S., Gluck, I.M., Tourlomousis, P., Wright, J.A., Cicuta, P., Monie, T.P., Bryant, C.E. (2014) Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA. 111: 7403-7408.

Man, S.M*., Ekpenyong, A.E*., Tourlomousis, P., Achouri, S., Cammarota, E., Hughes, K., Rizzo A., Ng, G., Wright, J.A., Cicuta, P., Guck, J., Bryant, C.E. (2014) Actin polymerization as a key innate immune effector mechanism to control Salmonella infection. Proc Natl Acad Sci USA. 111:17588–17593.*Co-first author.

  • Featured in Nature Reviews Immunology: Research Highlights: Leavy, O. (2015) Stiffening up defences against Salmonella. Nature Reviews Immunology. 15:4.
  • Recommended by Faculty of 1000 (F1000).

Zaki, M.H, Man, S.M., Vogel, P., Lamkanfi, M., Kanneganti, T.D. (2014) Salmonella exploits NLRP12–dependent innate immune signaling to suppress host defenses during infection. Proc Natl Acad Sci USA. 111:385-90.

  • Recommended by Faculty of 1000 (F1000).

Kuriakose, T., Man, S.M., Malireddi, R.K.S., Karki, R., Kesavardhana, S., Place,D.E., Neale, G., Vogel, P., Kanneganti, T.D. (2016) ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Science Immunology. 1:aag2045.

  • Featured in Cell Host & Microbe: Previews: Clancy, D.M., Martin S.J. (2016) Getting a gRIP on Flu by Casting the DAI. Cell Host & Microbe. 20:552–554.

Qi, X*., Man, S.M*., Malireddi, R.K.S., Karki, R., Lupfer, C., Gurung, P., Neale, G., Guy, C.S., Lamkanfi, M., Kanneganti, T.D. (2016) Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. Journal of Experimental Medicine. 213:2081-2097. *Co-first author.

Karki, R., Man. S.M., Malireddi, R.K.S., Gurung, P., Vogel, P., Lamkanfi, M., Kanneganti, T.D. (2015) Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection. Cell Host & Microbe. 17:357-368.

  • Featured in Cell Host & Microbe: Previews: Tomalka, J., Hise, A.G. (2015) Inflammasomes in aspergillosis – It takes two to tango. Cell Host & Microbe. 17:290-292.
  • Recommended by Faculty of 1000 (F1000).

Enosi Tuipulotu, D.,* Feng, S.,* Pandey, A., Zhao, A., Ngo, C., Mathur, A., Lee, J., Shen, C., Fox, D., Xue, Y., Kay, C., Kirkby, M., Lo Pilato, J., Kaakoush, N.O., Webb, D., Rug, M., Robertson, A.A.B., Tessema, M.B.,Pang, S., Degrandi, D., Pfeffer, K., Augustyniak, D., Blumenthal, A., Miosge, L.A.,Brüstle, A., Yamamoto, M., Reading, P.C.,Burgio, G., and Man, S.M. ‡ (2023) Immunity against Moraxella catarrhalis requires guanylate-binding proteins and inflammasomes. The EMBO Journal. 42:e112558. *Co-first author. ‡ Senior author.

Mathur, A.,* Kay, C.,* Xue, Y., Pandey, A., Lee, J., Jing, W., Enosi Tuipulotu, D., Lo Pilato, J., Feng, S., Ngo, C., Zhao, A., Shen, C., Rug, M., Miosge, L.A., Atmosukarto, I.I., Price, J.D., Ali, S.A., Gardiner, E.E., Robertson, A.A.B., Awad, M.M., Lyras, D., Kaakoush, N.O.,and Man, S.M. ‡ (2023) Clostridium perfringens virulence factors are nonredundant activators of the NLRP3 inflammasome. EMBO Reports. e54600. *Co-first author. ‡ Senior author.

 

SELECTED REVIEWS

Man, S.M., Jenkins, B.J. (2022) Context-dependent functions of pattern recognition receptors in cancer. Nature Reviews Cancer. 22:397-413.

Man, S.M., Kanneganti, T.D. (2016) Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nature Reviews Immunology. 16:7-21.

Man, S.M. (2018) Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis. Nature Reviews Gastroenterology & Hepatology. 15:721–737.

Man, S.M. (2011) The clinical importance of emerging Campylobacter species. Nature Reviews Gastroenterology & Hepatology. 8:669-685.

Man, S.M., Kaakoush, N.O., Mitchell, H.M. (2011) The role of bacteria and pattern-recognition receptors in Crohn’s disease. Nature Reviews Gastroenterology & Hepatology. 8:152-168.

Kirkby, M., Enosi Tuipulotu, D., Feng, S., Lo Pilato, J., Man, S.M. (2023) Guanylate-binding proteins: mechanisms of pattern-recognition and antimicrobial functions. Trends in Biochemical Sciences. 48:883-893.

Pandey, A*., Shen, C*., Feng, S*., Man, S.M. (2021) Cell biology of inflammasome activation. Trends in Cell Biology. 31:924-939. *Co-first author.

Enosi Tuipulotu, D., Mathur, A., Ngo, C., Man, S.M. (2021) Bacillus cereus: epidemiology, mechanisms of disease and host-pathogen interactions. Trends in Microbiology. 29:458-471.

Xue, Y*., Enosi Tuipulotu, D*., Tan, W.H., Kay, C., Man, S.M. (2019) Emerging activators and regulators of inflammasomes and pyroptosis. Trends in Immunology. 40:1035-1052. *Co-first author.

Kaakoush, N.O., Castaño Rodriguez, N., Man, S.M., Mitchell, H.M. (2015) Is Campylobacter to esophageal adenocarcinoma as Helicobacter is to gastric adenocarcinoma? Trends in Microbiology. 23:455-462.

Research centre

Stories »

Dr Abhimanu Pandey JCSMR Dr Abhimanu Pandey wins the Dewar-Milne Prize for outstanding thesis in Immunology for 2022 »

Contacts

Professor Si Ming Man
+61 2 612 56793
siming.man@anu.edu.au