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Experimental Medicine and Pathophysiology
Junior Principal Investigator / Group Leader at Humanitas Research Hospital, Adaptive Immunity Lab
Education and Academic Background
Marinos Kallikourdis read Natural Sciences in Trinity College, Cambridge (UK) under the supervision of M.S. Neuberger, where he also received a PhD in Immunology for work done in the MRC Laboratory of Molecular Biology (Cambridge, UK) in the group of A.G. Betz. He was part of the team that first demonstrated the requirement for regulatory T cells in the sustenance of maternal-fetal tolerance and deciphered the mechanism of pregnancy-associated amelioration of Rheumatoid Arthritis. After a short post-doc in the MRC-LMB and at Istituto Clinico Humanitas, he became a junior Principal Investigator in Humanitas and Assistant Professor of General Pathology and Immunology in the Department of Medical Biotechnology and Translational Medicine, University of Milan. In 2015 he became Assistant Professor of General Pathology and Immunology at Humanitas University.
I formally commenced teaching as a college supervisor for Biochemistry at Trinity College, Cambridge, whilst studying for my PhD. In the collegiate supervision system, great emphasis is given at stimulating the students’ ability to use their reasoning in order to ask and decipher complex scientific questions; this centuries-old principle remains a key guideline to how I approach lecturing.
As a faculty member of the University of Milan (2012-2015), I taught Adaptive Immunity modules in the english-language Medical School as well as in the Italian-language BSc and MSc Medical Biotechnology courses. I also ran an elective course, designed to expose students to the uncertain and often contradictory arrangement of information in the scientific literature.
In Humanitas University I teach a segment of the Mechanisms of Diseases integrated course in the Medical School (in english), as well as sections of the Nursing Course (in Italian), in all cases with a focus on Adaptive Immunity and closely related subjects. I also run an elective course on scientific communication.
Scientific and Research Interests
Cardiovascular disease and cancer are key causes of morbidity and mortality, creating an urgent clinical need to develop novel therapeutic approaches. Recent data increasingly suggest that inflammation and immune responses are implicated in the pathogenesis of many of these disorders.
My lab is interested in deciphering the interactions between the adaptive immune system and different tissues during disease pathogenesis. We study the mechanisms underlying these interactions, from a systemic down to molecular level. We then utilize the findings to attempt innovative, proof-of-principle therapeutic strategies for cardiovascular disease, cancer, as well as for conditions of multi-morbidity, where the above systems interact and cross-react.
As an example of the application of the above rationale, we have recently demonstrated that pro-inflammatory T cells, which are used therapeutically to treat tumors, may be simultaneously mediating pro-tumoral effects (Garetto et al., Oncotarget 2016). The identification and deciphering of this unexpected effect may pave the way for the refinement of current immunotherapeutic strategies for cancer.
In an even more recent study, we identified, via immunophenotyping at different stages of the disease, an association between the presence of T cells and heart failure (HF), both in experimental models and in human HF patient biopsies. On the basis of this finding, we then utilized an FDA-approved drug that interferes with T cell function in order to treat experimentally-induced HF. Treatment resulted in a block of progression of HF, in a manner substantially more efficient than current standard drugs targeting cardiac disease (Kallikourdis et al, Nature Communications 2017).
For a more general overview, see Kallikourdis, Cancer Immunol Immunother 2018.
For more details please visit: humanitas-research.org/marinos-kallikourdis/
Kallikourdis M*, Martini E, Carullo P, Sardi C, Roselli G, Greco C, Vignali D, Riva F, Ormbostad Berre AM, Stølen TO, Fumero A, Faggian G, Di Pasquale E, Elia L, Rumio C, Catalucci D, Papait R, Condorelli G* (2017) – T cell costimulation blockade blunts pressure overload-induced heart failure. Nature Communications 8, 14680 doi: 10.1038/ncomms14680 (*:corresponding and supervizing authors)
Kallikourdis M (2018) – T cell responses to tumor: how dominant assumptions on immune activity led to a neglect of pathological functions, and how evolutionary considerations can help identify testable hypotheses for improving immunotherapy. Cancer Immunol Immunother (in press)
Garetto S, Sardi C, Martini E, Roselli G, Morone D, Angioni R, Cianciotti BC, Trovato AE, Franchina DG, Castino GF, Vignali D, Erreni M, Marchesi F, Rumio C and Kallikourdis M* (2016) – Tailored chemokine receptor modification improves homing of adoptive therapy T cells in a spontaneous tumor model. Oncotarget 7(28), 43010-43026. doi: 10.18632/oncotarget.9280. (*:corresponding author)
Garetto S, Trovato AE, Sala F, Lleo A, Martini E, Betz AG, Norata GD, Invernizzi P and Kallikourdis M* (2015) – Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment. Immunobiology 220(8), 1025-1029. doi: 10.1016/j.imbio.2015.02.006. (*:corresponding author)
Kallikourdis M(*), Trovato AE, Anselmi F, Sarukhan A, Roselli G, Tassone L, Badolato R and Viola A (2013) – The CXCR4 mutations in WHIM syndrome impair the stability of the T cell immunological synapse. Blood 2013;122:666-73. (*:corresponding author)
Suano AM*, Kallikourdis M*, Sarris M* and Betz AG, (2012) – Regulatory T cells protect from autoimmune arthritis during pregnancy, J Autoimmunity 38, J103-8. (*=contributed equally)
Aluvihare V, Kallikourdis M & Betz A (2004) – Regulatory T Cells Mediate Maternal Tolerance to the Fetus. Nat Immunol 5, 266-271.
Bystry RS, Aluvihare V, Welch KA, Kallikourdis M & Betz AG (2001) – B Cells and Professional APCs Recruit Regulatory T Cells Via CCL4. Nat Immunol 2, 1126-1132.