The innate immune system provides the first line of defense against microbes and other foreign substances. Innate immune detections of and responsiveness to microbes is mediated by sets of receptors known as pattern recognition receptors (PRRs). PRRs include Toll-like receptors (TLRs), found on the cell surface or endosomal compartments and intracellular receptors such as NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) cytoplasmic DNA sensors. Activation of PRRs results in the production of a large set of proinflammatory cytokines and type I interferons (IFNs), which act concertedly to coordinate host defenses against foreign invasion. Although meant to protect the host, excessive or deregulated induction of these innate immune responses, can lead to self-injury (e.g. during sepsis or autoimmune diseases). Therefore, in order to maintain an optimal balance between anti-microbial host defenses and protection from self-harm, PRR signaling pathways must be regulated tightly. We are interested in understanding the mechanisms that govern the regulation of PRRs signaling pathways and how the breakdown of such regulation may lead to inflammation or impair anti-microbial host defenses. In particular, we are interested in how DNA damage and the ubiquitin system modulate inflammatory responses.

Methods:
In vivo mouse models of inflammation and infections (bacteria and viruses). In vitro studies using a variety of techniques including flow cytometry, microscopy, lentiviral transduction, mass spectrometry, cell culture, protein biochemistry, and cell/molecular biology techniques.

Second affiliation: The Laboratory for Infection Medicine Sweden (MIMS) – Umeå University (http://www.mims.umu.se/groups/nelson-gekara.html)

Selected publications:

• Jiang H, Xue X, Panda S, Kawale A, Hooy RM, Liang F, Sohn J, Sung P, Gekara NO. Chromatin-bound cGAS is an inhibitor of DNA repair and hence accelerates genome destabilization and cell death. EMBO J. 2019 Sep 23:e102718. doi: 10.15252/embj.2019102718.
• Erttmann SF, Gekara NO. Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity. Nat Commun. 2019 Aug 2;10(1):3493. doi: 10.1038/s41467-019-11169-x..
• Gekara NO, Jiang H. The innate immune DNA sensor cGAS: A membrane, cytosolic, or nuclear protein? Sci Signal. 2019 May 14;12(581). pii: eaax3521. doi: 10.1126/scisignal.aax3521. Review.
• Panda S, Gekara NO. The deubiquitinase MYSM1 dampens NOD2-mediated inflammation and tissue damage by inactivating the RIP2 complex. Nat Commun. 2018 Nov 7;9(1):4654.

• Gekara, NO. DNA damage-induced immune response: Micronuclei provide key platform. Journal of Cell Biology 2017, August 31 216 (10). 2999-3001.

• Putzova D, Panda S, Härtlova A, Stulík J, Gekara NO. Subversion of innate immune responses by Francisella involves the disruption of TRAF3 and TRAF6 signalling complexes. Cell Microbiol. 2017 Nov;19(11).

• Erttmann SF, Härtlova A, Sloniecka M, Raffi FA, Hosseinzadeh A, Edgren T, Rofougaran R, Resch U, Fällman M, Ek T, Gekara NO. Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity. Immunity. 2016 Jul 19;45(1):106-18.

• Panda S, Nilsson JA and Gekara NO. Deubiquitinase MYSM1 regulates innate immunity through inactivation of TRAF3 and TRAF6 complexes. Immunity. 2015 Oct 13;43(4).

• Härtlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kröger A, Nilsson JA, Ek T, Weiss S, Gekara NO. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity. 2015 Feb 17;42(2):332-43.

• Dietrich N, Rohde M, Geffers R, Kroeger A, Hauser H, Weiss S and Gekara NO. Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria. Proc Natl Acad Sci U S A. 2010 May 11 Vol 107(19):8748-53.

• Gekara NO, Zietara N, Geffers R and Weiss S. L. monocytogenes induces T cell receptor unresponsiveness via its pore forming toxin Listeriolysin O. Journal of Infectious Diseases. Dec 2010. Vol 202(11):1698-707.

• Dietrich N, Lienenklaus S, Weiss S and Gekara NO. Murine Toll-Like Receptor 2 Activation Induces Type I Interferon Responses from Endolysosomal Compartments. PLoS One. April 2010. Vol 5 (4): e10250.

Current Members of the Gekara Group

Hui Jiang, Postdoc Umeå University

Michaela Annemman, Umeå University

Swarupa Panda, Ph.D student, Umeå University

Patrycja Swacha, Project assistant, Umeå University

Loureen Oduor Msc. Student (Örebro University)

Alumni

Saskia F. Erttmann Postdoc, Umeå University, (Currently assistant professor, Umeå University: https://www.umu.se/en/staff/saskia-erttmann)

Anetta Härtlova, Postdoc, Umeå University, (Currently, assistant professor, Gothernborg University: https://biomedicine.gu.se/personal/avd-for-mikrobiologi-och-immunologi?userId=xsvian)

Gaurav Gupta, Postdoc, Umeå University

Ulrike Resch, Postdoc, Umeå University

Sandrine Le Roux, Postdoc, Umeå University

Daniela Putzova, exchange PhD student (Hradec Kralove, Czech Republic)

Salah Farag Ibrahim, PhD student, Umeå University

Marta Sloniecka, PhD student, Umeå University

Anja Schmalz, research technician, Umeå University

Lalitha Tadala, BSc and MSc student, Umeå University

Sharath Anugula, BSc and MSc student, Umeå University

Faizal Ali Mohamed Raffi, BSc and MSc student, Umeå University

Patrycja Swacha, Msc exchange student (Krakow, Poland)

Ler Wei Xuan, Msc Student exchange Singapore

Ayse Seda Yazgili, BSc exchange student (Istanbul, Turkey)

Marylin Thölken, technician intern (Göttingen, Germany)

Laura Jordt, BSc exchange student (Greifswald, Germany)

Johanna Heine, technician intern (Göttingen, Germany)

Moa Lindgren, BSc student Umeå University

Anton Persson, BSc student, Umeå University