Mirela Kuka (MK) is Professor of General Pathology at Università Vita-Salute San Raffaele and tenure-track Project Leader in the Division of Immunology (DITID) at the San Raffaele Scientific Institute (Milan). MK obtained her Ph.D within the DC-Thera European Network at the University of Siena/Novartis Vaccines after working at projects aimed at studying dendritic cell (DC) maturation. She then moved to the National Institutes of Health (US) for her first postdoctoral training to study T cell responses and their interactions with DC upon viral infection. In 2013 MK joined our institute to continue her studies, first as a EU-funded senior postdoctoral fellow in Matteo Iannacone’s team, and since 2016 as a Principal Investigator. 

MK is an active member of the American Association of Immunologists (AAI), the Italian Association of Immunologists (SIICA), and the Italian Network for Tumor Biotherapy (NIBIT). Moreover, she is vice-coordinator of the PhD Curriculum in Basic and Applied Immunology and Oncology (International PhD Program in Molecular Medicine, UniSR), and member of the OSR Institutional Seminars Committee and of the DITID Divisional Seminars Committee (San Raffaele Scientific Institute). Finally, MK is an active reviewer of journals publishing immunology studies (Cell Death & Disease, Science Immunology, Cellular & Molecular Immunology, European Journal of Immunology, Frontiers in Immunology).

A full list of her publications can be found at https://pubmed.ncbi.nlm.nih.gov/?term=kuka+m

RESEARCH ACTIVITY

MK's research activity focuses on investigating the role of the immune system in different pathological contexts, with a particular interest at the interplay between innate and adaptive immunity. In particular, over the recent years, MK has been intrigued by the innate and adaptive immune mechanisms regulating B cell responses to viral infections. To understand where and when B cells are activated in response to viruses, she and her collaborators have been taking a comprehensive approach in studying the interacting partners of B cells, both those that support and those that suppress B cell activation and humoral responses {Kuka and Iannacone, 2021}. For example, they have found that T cell help to B cells is dependent on the fine spatiotemporal regulation of molecular mechanisms that result in significant differences in antiviral responses, with some viruses leading to extreme T helper 1 responses that might cross-antagonize and suppress T follicular helper cells and B cell activation {De Giovanni et al., 2020; Kuka et al., 2019; Sala et al. submitted}. In addition, they have described for the first time that inflammatory monocytes recruited upon some viral infections can directly suppress humoral responses by inducing B cell apoptosis {Sammicheli et al., 2016; Kuka and Iannacone, 2018; Sala and Kuka, 2020}. During these years, MK has established collaborations with several groups within and outside the institute and built a solid track record on mouse models of viral infections, and B and T cell biology. 

In the future, besides continuing her work on viral infections, MK would like to explore whether mechanisms regulating B cell responses during infection occur also in other pathological settings, for example in tumors. The role of B cells in tumors is emerging as crucial, since in more and more cancer settings the presence of B cell-containing tertiary lymphoid structures (TLS) correlates with response to immunotherapy and with a good clinical prognosis {Conejo-Garcia et al., 2023; Fridman et al., 2022}. However, the majority of these studies are performed with human samples that don’t allow for mechanistic studies. MK and her team aim to characterize the cellular and molecular mechanisms whereby B cells influence tumor progression and to shed light on how B cells are regulated within tumors by performing mechanistic experiments with animal models. Knowledge arising from these studies might shed new light on the crosstalk between cancer and the immune system, might unravel an underappreciated role for B cells in anti-tumor immunity, and might lay the basis for novel immunotherapeutic approaches with the potential of boosting the B cell response in tumors. 

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