Professor Si Ming Man

PhD
Group Leader, Department of Immunology and Infectious Disease
College of Health & Medicine
T: +61 612 56793

Areas of expertise

  • Medical Microbiology 1108
  • Cancer Cell Biology 111201
  • Tumour Immunology 110709
  • Oncology And Carcinogenesis 1112
  • Gastroenterology And Hepatology 110307
  • Infectious Diseases 110309
  • Medical Bacteriology 110801
  • Infectious Agents 060502
  • Medical Infection Agents (Incl. Prions) 110802
  • Medical Biochemistry And Metabolomics 1101
  • Innate Immunity 110707
  • Immunology 1107
  • Microbiology 0605
  • Bacteriology 060501

Research interests

Our lab investigates the role of innate immunity in infectious diseases and cancer. Pattern-recognition receptors are germ-line encoded 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 use cutting-edge technology to study the mechanisms by which host sensors recognise bacteria, viruses and parasites, and 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 the molecular basis by which uncontrolled inflammation can lead to the development of cancer, autoimmunity and inflammatory diseases.

We welcome applications from undergraduate, Honours and PhD students, and research assistants and Postdoctoral fellows. We offer Summer Scholarships and Short Projects (e.g. Advanced Studies Course/ASC, SCNC2101 and SCNC3101, and BIOL3208). E-mail Si Ming (siming.man@anu.edu.au) for further information regarding project details and position availability.

Biography

Si Ming received his BMedSc from UNSW Sydney (Honours Class I and the University Medal) and Ph.D. from the University of Cambridge in 2013 for his work on inflammasomes in the host defence against Salmonella infection. He obtained his postdoctoral training from St. Jude Children’s Research Hospital, USA, where he studied immune signalling pathways in the host response to infection and cancer. Currently, he is a CSL Centenary Fellow at the Australian National University, Australia, where his laboratory focuses on innate immunity in the host defence against infectious diseases and the development of cancer and other chronic diseases.

In 2020, Si Ming was named a Clarivate™ Highly Cited Researcher for producing, in the last decade, multiple highly-cited papers that rank in the top 1% by citations for field and year in the Web of Science™.

Awards and recognition:

  • CSL Centenary Fellowship (2021)
  • The Australian Society for Medical Research Peter Doherty Leading Light Award (2020)
  • The Australian Society for Biochemistry & Molecular Biology Eppendorf Edman Early Career Award (2020)
  • The Commonwealth Health Minister's Medal for Excellence in Health and Medical Research (2019)
  • The Royal Society of NSW Edgeworth David Medal (2019)
  • NHMRC Research Excellence Award for the highest-ranked Career Development Fellowship Biomedical Level 1 (2019).
  • The American Association of Immunologists Pfizer-Showell Award (2019)
  • The Australian Society for Microbiology Jim Pittard Early Career Award (2017)
  • The American Association of Immunologists Thermo Fisher Trainee Achievement Award (2016) 
  • The International Cytokine & Interferon Society Milstein Young Investigator Award (2016)
  • NHMRC Research Excellence Award for the highest-ranked Early Career Fellowship (2015)

Si Ming gives lectures in the following ANU undergraduate courses: BIOL3144 Advanced and Applied Immunology; BIOL3108 Hallmarks of Cancer.

Researcher's projects


Possible project areas we have available include:

  • Uncovering how host cells, such as macrophages, recognise and kill human pathogens, including bacteria (such as Salmonella, Clostridium, Listeria, Francisella, and Bacillus) and viruses (Influenza, MCMV, HSV, and SARS-COV-2/COVID19).
  • Unravelling the molecular mechanisms of inflammasome formation.
  • Understanding the role of innate immune sensors in regulating the development of cancer, such as small intestinal cancer, colorectal (bowel) cancer, and melanoma, and the composition of the gut microbiota.
  • Identifying novel activators and inhibitors of the immune system to prevent and treat infection, autoinflammatory diseases and cancer.

Current and past theses of PhD students:

  • 2017-2021: Microbial activators of the inflammasome; Awarded the Sidney & Joan Pestka Graduate Award from the International Cytokine & Interferon Society, the Australian Society for Biochemistry & Molecular Biology (ASBMB) Fellowship, the Australian Society for Microbiology Nancy Millis Award NSW/ACT, and the Cells 2021 PhD Thesis Award
  • 2018-2022: The role of guanylate-binding proteins in the host defence against infectious diseases; Awarded the Cold Spring Harbor Best Poster Prize and the Australian Society for Microbiology NSW/ACT Branch Student Travel Award
  • 2018-2022: The role of cytosolic nucleic acid sensors in colitis and intestinal cancer; Published in Trends in Cell Biology and Nature Communications
  • 2018-2022: Inflammasomes in tumourigenesis; Published in Trends in Cell Biology, Cell Research, and Yale Journal of Biology & Medicine
  • 2022-2024: DNA sensors in infection and immunity
  • 2022-2024: Cell-type-specific roles of immune activation

 

Current and past theses of Honours students:

  • 2021: DNA sensing in Listeria infection, Awarded First Class Honours
  • 2020-2021: The molecular mechanism of alpha-toxin-induced inflammasome activation in response to Clostridium septicum infection, Awarded First Class Honours and the University Medal
  • 2019: Clostridium perfringens is a novel activator of the NLRP3 inflammasome,  Awarded First Class Honours and the University Medal
  • 2018-2019: Transmembrane regions of the pore-forming toxin Haemolysin BL are required for inflammasome activation but not membrane binding, Awarded First Class Honours and the University Medal
  • 2018: Molecular mechanisms of inflammasome activation by enterotoxins of the foodborne pathogen Bacillus cereus, Awarded First Class Honours
Techniques you will learn: Western blots, genetic engineering, cloning, molecular biology and protein techniques, ELISA, electron microscopy, confocal microscopy, liposome technology, mammalian and bacterial cell culture.

 

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.

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.

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.

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).

 

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.

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.

Publications

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Updated:  14 August 2022 / Responsible Officer:  Director (Research Services Division) / Page Contact:  Researchers