CECAD Microsite

Overview

Inflammation is a response of the immune system that aims to defend the organism from pathogens and to promote wound healing and tissue regeneration in response to injury and infection. However, excessive or prolonged inflammation causes tissue damage and is involved in the pathogenesis of a plethora of inflammatory diseases. Chronic inflammation is also implicated in cancer development as well as in ageing and ageing-associated pathologies. Therefore, inflammatory responses need to be tightly regulated to ensure effective host defence and injury repair while preventing excessive tissue pathology and disease. This fine balance between the beneficial and potentially detrimental sides of inflammation is critical for the maintenance of tissue homeostasis and organismal health. Our research aims to understand the mechanisms that regulate inflammation and the pathogenesis of inflammation-related diseases, ultimately aspiring to develop better therapeutic approaches. 

 

 

Selected publications

Jiao H, Wachsmuth L, Kumari S, Schwarzer R, Lin J, Eren RO, Fisher A, Lane R, Young GR, Kassiotis G, Kaiser WJ, Pasparakis M (2020) Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. Nature 580: 391-395

Schwarzer R, Jiao H, Wachsmuth L, Tresch A, Pasparakis M (2020) FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells. Immunity 52: 978-993 e6

Laurien L, Nagata M, Schunke H, Delanghe T, Wiederstein JL, Kumari S, Schwarzer R, Corona T, Kruger M, Bertrand MJM, Kondylis V, Pasparakis M (2020) Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation. Nat Commun 11: 1747

Polykratis A, Martens A, Eren RO, Shirasaki Y, Yamagishi M, Yamaguchi Y, Uemura S, Miura M, Holzmann B, Kollias G, Armaka M, van Loo G, Pasparakis M (2019) A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis through its ZnF7 ubiquitin-binding domain. Nat Cell Biol 21: 731-742

Eftychi C, Schwarzer R, Vlantis K, Wachsmuth L, Basic M, Wagle P, Neurath MF, Becker C, Bleich A, Pasparakis M (2019) Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment. Immunity 51: 367-380 e4

Vlantis K, Wullaert A, Polykratis A, Kondylis V, Dannappel M, Schwarzer R, Welz P, Corona T, Walczak H, Weih F, Klein U, Kelliher M, Pasparakis M (2016) NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-kappaB-Dependent and -Independent Functions. Immunity 44: 553-567

Lin J, Kumari S, Kim C, Van TM, Wachsmuth L, Polykratis A, Pasparakis M (2016) RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature 540: 124-128

Kondylis V, Polykratis A, Ehlken H, Ochoa-Callejero L, Straub BK, Krishna-Subramanian S, Van TM, Curth HM, Heise N, Weih F, Klein U, Schirmacher P, Kelliher M, Pasparakis M (2015) NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis. Cancer Cell 28: 582-598

Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, Eftychi C, Lin J, Corona T, Hermance N, Zelic M, Kirsch P, Basic M, Bleich A, Kelliher M, Pasparakis M (2014) RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513: 90-4

Welz PS, Wullaert A, Vlantis K, Kondylis V, Fernández-Majada V, Ermolaeva M, Kirsch P, Sterner-Kock A, van Loo G, Pasparakis M (2011) FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477 (7364): 330-4

 

 

For full list of publications click here:

Recent Publications

OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice
Hannah Schünke et al., Nature Commun 12: 5912 (2021)
https://doi.org/10.1038/s41467-021-25945-1
SharedIt link: https://rdcu.be/cy8JC

Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation
Nikos Oikonomou et al., Mucosal Immunology 14: 1160-1171 (2021)
https://doi.org/10.1038/s41385-021-00415-5
SharedIt link: rdcu.be/clpjF

NF-κb inhibition in keratinocytes causes RIPK1-mediated necroptosis and skin inflammation
Snehlata Kumari et al., Life Science Alliance vol.4: no.6, e20200956 (2021)
https://doi.org/10.26508/lsa.202000956
Download the accepted manuscript here

FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells
Robin Schwarzer et al., Immunity 52: 978-993.e6 (2020)
https://doi.org/10.1016/j.immuni.2020.04.002
Download the accepted manuscript here

Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation
Lucie Laurien et al., Nature Commun 11: 1747 (2020)
https://doi.org/10.1038/s41467-020-15466-8

Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation
Huipeng Jiao et al., Nature 580: 391-395 (2020)
https://doi.org/10.1038/s41586-020-2129-8
SharedIt link: https://rdcu.be/b3eqA