Our research has two main directions:

• a basic science path aiming to understand mechanisms of host-fungal interplay with emphasis on molecular interactions in the phagosome
• a translational path that explores mechanisms of immune dysfunction leading to development of IMI and immunomodulatory strategies aiming to restore phagocyte defects in patients at high risk for IMI.

To achieve our goals in part (i) of our research we utilize:

• Multi-omics approaches in primary immune cells and isolated phagosomes to identify novel antifungal effector pathways and their regulation by cell metabolism
• In vivo genetic screens in Drosophila melanogaster RNAi strains to identify evolutionarily conserved antifungal host defense mechanisms in phagocytes
• Advanced bioimaging tools, molecular and biochemical approaches to functionally validate the physiological importance of novel host effectors
• Transgenic mice to explore the role of identified host pathways and pathogen effectors in physiological antifungal immunity and disease pathogenesis.

To achieve our goals in part (ii) of our research we participate in International Collaborative Networks (TRANS-CPA and HDM-FUN) aiming to understand
pathogenesis and mechanisms of response to immunotherapy in patients with IMI. In parallel, we perform prospective biobanking of clinical samples from
immunocompromised patients of interest and maintain an expanding collection of tissue biopsies from patients with IMI diagnosed at the University Hospital of
Heraklion, Crete. Ongoing clinical protocols allow for assessment of the immunomodulatory activity of clinically-approved compounds on phagosome
biogenesis and macrophage immunometabolism. Finally, in order to dissect interesting immune phenotypes identified in human studies, we perform
mechanistic studies in physiologically relevant mouse models of IMI.

Selected Publications:

1. Pikoulas A, Morianos I, Nidris VN, Hamdy R, López-López A, Moran-Garrido M, Muthu V, Halabalaki M, Papadovasilaki M, Irene K, Gu Y, Aerts R, Mercier T, Vanbiervliet Y, Cho SY, Spallone A, Samonakis D, Kastritis E, Drakos E, Tzardi M, Eliopoulos A, Georgila K, Carvalho A, Kurzai O, Rudramurthy S, Lanternier F, Petratos K, Maertens J, Bruno V, Kontoyiannis D, Barbas C, Soliman S, Ibrahim A, Chamilos G*. Albumin orchestrates a natural host defense mechanism against mucormycosis. Res Sq [Preprint]. 2024 Dec 3:rs.3.rs-5441197. doi: 10.21203/rs.3.rs-5441197/v1. * Corresponding author
2. Seldeslachts L, Staels F, Gkountzinopoulou M, Jacobs C, Tielemans B, Vanhoffelen E, Reséndiz-Sharpe A, De Herdt L, Haughton J, Prezzemolo T, Burton O, Feys S, van de Veerdonk FL, Carvalho A, Naesens L, Matthys P, Lagrou K, Verbeken E, Chamilos G, Wauters J, Humblet-Baron S, Vande Velde G. Damping excessive viral-induced IFN-γ rescues the impaired anti-Aspergillus host immune response in influenza-associated pulmonary aspergillosis. EBioMedicine. 2024 Oct;108:105347. doi: 10.1016/j.ebiom.2024.105347.
3. Akoumianaki T, Vaporidi K, Diamantaki E, Pène F, Beau R, Gresnigt MS, Gkountzinopulou M, Venichaki M, Drakos E, El-Benna J, Samonis G, Le KTT, Kumar V, Georgopoulos D, van de Veerdonk FL, Netea MG, Latge JP, Chamilos G*. Uncoupling of IL-6 signaling and LC3-associated phagocytosis drives immunoparalysis during sepsis. Cell Host Microbe. 2021 Aug 11;29(8):1277-1293.e6. doi: 10.1016/j.chom.2021.06.002.* Corresponding author
4. Soliman SSM, Baldin C, Gu Y, Singh S, Gebremariam T, Swidergall M, Alqarihi A, Youssef EG, Alkhazraji S, Pikoulas A, Perske C, Venkataramani V, Rich A, Bruno VM, Hotopp JD, Mantis NJ, Edwards JE Jr, Filler SG, Chamilos G, Vitetta ES, Ibrahim AS. Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis. Nat Microbiol. 2021 Mar;6(3):313-326. doi: 10.1038/s41564-020-00837-0.
5. Andrianaki AM, Kyrmizi I, Thanopoulou K, Baldin C, Drakos E, Soliman SSM, Shetty AC, McCracken C, Akoumianaki T, Stylianou K, Ioannou P, Pontikoglou C, Papadaki HA, Tzardi M, Belle V, Etienne E, Beauvais A, Samonis G, Kontoyiannis DP, Andreakos E, Bruno VM, Ibrahim AS, Chamilos G*. Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species. Nat Commun. 2018 Aug 20;9(1):3333. doi: 10.1038/s41467-018-05820-2.* Corresponding author
6. Kyrmizi I, Ferreira H, Carvalho A, Figueroa JAL, Zarmpas P, Cunha C, Akoumianaki T, Stylianou K, Deepe GS Jr, Samonis G, Lacerda JF, Campos A Jr, Kontoyiannis DP, Mihalopoulos N, Kwon-Chung KJ, El-Benna J, Valsecchi I, Beauvais A, Brakhage AA, Neves NM, Latge JP, Chamilos G*. Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling to prevent LC3-associated phagocytosis. Nat Microbiol. 2018 Jul;3(7):791-803. doi: 10.1038/s41564-018-0167-x. * Corresponding author
7. Akoumianaki T, Kyrmizi I, Valsecchi I, Gresnigt MS, Samonis G, Drakos E, Boumpas D, Muszkieta L, Prevost MC, Kontoyiannis DP, Chavakis T, Netea MG, van de Veerdonk FL, Brakhage AA, El-Benna J, Beauvais A, Latge JP, Chamilos G*. Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity. Cell Host Microbe. 2016 Jan 13;19(1):79-90. doi: 10.1016/j.chom.2015.12.002. * Corresponding author
8. Kyrmizi I, Gresnigt MS, Akoumianaki T, Samonis G, Sidiropoulos P, Boumpas D, Netea MG, van de Veerdonk FL, Kontoyiannis DP, Chamilos G*. Corticosteroids block autophagy protein recruitment in Aspergillus fumigatus phagosomes via targeting dectin-1/Syk kinase signaling. J Immunol. 2013 Aug 1;191(3):1287-99. doi: 10.4049/jimmunol.1300132. * Corresponding author
9. Chamilos G, Gregorio J, Meller S, Lande R, Kontoyiannis DP, Modlin RL, Gilliet M. Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood. 2012 Nov 1;120(18):3699-707. doi: 10.1182/blood-2012-01-401364.
10. Chamilos G, Lewis RE, Hu J, Xiao L, Zal T, Gilliet M, Halder G, Kontoyiannis DP. Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis. Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9367-72. doi: 10.1073/pnas.0709578105.