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Cellular-Stress and Immune Response Laboratory

Cellular-Stress and Immune Response Laboratory

Cells are constantly exposed to several internal (metabolites, damaged macromolecules such as proteins and lipids) and external stimuli (e.g. microbes, radiations, temperature and chemicals) which stress the cells. A successful survival of an organism depends on how well it adapts to different stress. Cells survive these insults by mounting specific repair mechanisms such as oxidative stress response, unfolded protein response (UPR), and DNA damage response (DDR) which aid in regaining normal physiology. When they fail to restore homeostasis, they undergo cell death or they survive in a maladaptive phase resulting in pathologies such as malignancies, neurodegenerative, cardiovascular and metabolic disorders.  In our lab we investigate the function of these stress responses in innate immune defences, in the context of pathologies such as cancer and infection which will help in understanding disease pathogenesis and present novel targets for therapeutic treatments.

Current research projects

  • Significance of metabolic adaptations in the cell-autonomous defence against pathogens
  • Host-directed approaches to treat antibiotic-resistant microbes
  • Cell death mechanisms in infection and cancer
  • Organellar (Mitochondria, Endoplasmic Reticulum and Lysosomes) stress responses in cancer.

 

Publications

* Corresponding senior author

1. Fischer J, Guitèrrez S, Ganesan R, Calabrese C, Ranjan R, Cildir G, Hos NJ, Rybniker J, Wolke M, Fries JWU, Tergaonkar V, Plum G, Antebi A, Robinson N* (2019). Leptin signaling impairs macrophage defences against Salmonella Typhimurium. Proc Natl Acad Sci USA 116(33):16551-16560.

2. Robinson N*, Ganesan R, Hegedűs C, Kovács K, Kufer TA, Virág L (2019). Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos. Redox Biol 26:101239.

3. Chipurupalli S, Kannan E, Tergaonkar V, D'Andrea R, Robinson N* (2019). Hypoxia Induced ER Stress Response as an Adaptive Mechanism in Cancer. Int J Mol Sci. 20(3). pii: E749

4. Tiku V, Kew C, Mehrotra P, Ganesan R, Robinson N*, Antebi A* (2018). Fibrillarin is an evolutionarily conserved central regulator of pathogen resistance Nature Communications 9(1):3607

5. Robinson N*. (2018) Salmonella Typhimurium infection: Type I Interferons integrate cellular networks to disintegrate macrophages. Cell Stress 2(2): 37-39

6. Hos N, Ganesan R, Gutierrez S, Klimek J, Abdullah Z, Krönke M and Robinson N*. (2017)Type I interferon enhances necroptosis of Salmonella Typhimurium-infected macrophages by impairing anti-oxidative stress responses. J. Cell. Biol 216(12):4107-4121

7. Ganesan R, Hos N, Gutierrez S, Stepek J, Daglidu E, Fischer J, Krönke M and Robinson N*. (2017) Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy. PLoS Pathogens. 13(2): e1006227

8. Robinson N*. (2017) Typhi colonization factor (Tcf) genetically conserved yet functionally diverse. Virulence. 8(8): 1511-1512.

9. Gutiérrez S, Wolke M, Plum G, Robinson N*. (2017)Isolation of Salmonella typhimurium-containing Phagosomes from Macrophages. J Vis Exp. 128

10. Robinson N++, McComb S, Mulligan R, Dudani R, Krishnan L and Sad S. (2012) Type-I interferon induces necroptosis in macrophages during Salmonella Typhimurium infection. Nature Immunology 13(10):954-962.

11. Fischer J, Jung N, Robinson N, Lehmann C. (2015) Sex differences in immune responses to infectious diseases. Infection. 43(4): 399-403

12. Persa OD, Jazmati N, Robinson N, Wolke M, Kremer K, Schweer K, Plum G, Schlaak M. (2014) A pregnant woman with chronic meningococcaemia from Neisseria meningitidis with lpxL1-mutations. Lancet. 384(9957): 1900.

13. Nguyen T, Robinson N, Allison SE, Coombes BK, Sad S and Krishnan L. (2013) IL-10 produced by trophoblast cells inhibits phagosome maturation leading to profound intracellular proliferation of Salmonella enterica Typhimurium. Placenta 34(9):765-774.

14. Albaghdadi H, Robinson N, Dudani R, Krishnan L and Sad S. (2009) Selectively reduced intracellular proliferation of Salmonella Typhimurium within antigen-presenting cells limits antigen-presentation and development of a rapid CD8 T cell response. Journal of Immunology 183(6):3778-87.

15. Chattopadhyay A, Robinson N, Sandhu JK, Finlay BB, Sad S and Krishnan L. (2010) Salmonella Typhimurium induced placental inflammation and not bacterial burden correlates with pathology and fatal maternal disease. Infection and Immunity 78(5):2292-301.

16. Robinson N++, Kolter T, Rybniker J, Wolke M, Hartmann P, Plum G. (2008) A Mycobacterial glycolipid inhibits phagosome maturation and subverts proinflammatory cytokines. Traffic 9(11):1936-47

17. Rybniker J, Nowag A, van Gumpel E, Nissen N, Robinson N, Plum G and Hartmann P. (2010) Insights into the function of the WhiB-like protein of mycobacteriophage TM4 – a transcriptional inhibitor of WhiB2. Molecular Microbiology. 77(3): 642-57

18. Rybniker J, Plum G, Robinson N, Small PL and Hartmann P. (2008) Identification of three cytotoxic early proteins of mycobacteriophage L5 leading to growth inhibition in Mycobacterium smegmatis. Microbiology. 154 (Pt 8): 2304-14.

19.Robinson N++, Wolke M, Ernestus K, Plum G. (2007) A mycobacterial gene involved in synthesis of an outer cell envelope lipid is a key factor in prevention of phagosome maturation. Infection and Immunity 75(2): 581-591.

20. Stephen TL,  Fabri M, Groneck L, Röhn TA, Hafke H, Robinson N, Rietdorf J, Schrama D, Becker JC, Plum G, Krönke M, Kropshofer H, and Kalka-Moll WM. (2007) Transport of Streptococcus pneumoniae Capsular Polysaccharide in MHC Class II Tubules. PLoS Pathogens. 16;3(3):e32.