The deregulation of the immune system can lead to chronic conditions that are known as immune-mediated inflammatory diseases (IMIDs). IMIDs include more than 80 clinical entities such as autoimmune and autoinflammatory diseases that affect up to 10% of the population in the western world. Basic research has allowed to characterize physiological mechanisms responsible for controlling the development of inflammatory and adaptive responses mediating pathological effects, and this knowledge is critical to innovate at the level of strategies directed at the immune system and to understand the mechanism of action of drugs currently being used in the clinic.
Our group is interested in the study of cellular and molecular mechanisms that control the inflammatory process and the adaptive immune response. We focus on the biology of dendritic cells (DCs), since they constitute a sub-population of leukocytes able to orchestrate effector adaptive immune responses, while having powerful strategies capable of regulating the development of the inflammatory process and the adaptive response. Our work tries to cover relevant and original aspects at the level of molecular mechanisms while looking for pertinence in human health.
In this framework, the laboratory has characterized the emerging ion transporters TORID-1 (Tmem176b) and TORID-2 (Tmem176a), which are critical regulators of NLRP3 inflammasome activation. Inflammasome regulation by TORID-1 has been shown to be relevant in the anti-tumor immune response. We have characterized pharmacological inhibitors of TORID-1 and TORID-2 that have been characterized at a pre-clinical level as promising anti-tumor drugs.
Role of TORID-1 as an innate checkpoint in tumor immunity.
Role of TORID-1 and TORID-2 in the biology of chronic lymphocytic leukemia. (Collaboration with Pablo Oppezzo)
Characterization of small molecules capable of inhibiting or activating the conductance mediated by TORID-1 and 2.
Role of the intracellular protein TORID-1 in obesity and inflammation induced by obesity. (Collaboration with Carlos Escande)
Study of non-conventional anti-inflammatory drugs as immunomodulators in organ transplantation. (Collaboration with Carlos Batthyany)
“Challenges in cancer immunotherapy. International workshop”, 2018.
“Update on immunology: from mechanisms to immunotherapy and vice versa. Jornada Científica de la SUI”, 2016. Coordinators: Marcelo Hill, Maria Moreno and Mercedes Segovia.
“Basic and clinical fundamentals of the inflammatory process. Optional course in the Medicine career”, 2014. Faculty of Medicine. Coordinator: Dr. Marcelo Hill.
“Immunological bases of biological drugs used in Medicine”, 2013. Posgraduate course, Faculty of Medicine, Udelar. Coordinators: Dr. Marcelo Hill, Dra. Caroline Agorio and Dr. Eduardo Osinaga.
“Tolerance vs. Immunity: how and why?”, 2012. Course PEDECIBA. Coordinators: Dr. Teresa Freire and Dr. Marcelo Hill. Immunobiology Department, Faculty of Medicine, Udelar.
2017-2018 – Characterization of a new regulator of inflammation. ANII. FCE_3_2016_1_126894. Responsible: Mercedes Segovia.
2018-2019 – Pharmacological blockade of a new inhibitor of the anti-tumor immune response. ANII. FMV_1_2017_1_136177 Responsible: Marcelo Hill.
2015‐2018 – Development and validation of processes for the study and valuation of nutraceuticals: creation of the first Uruguayan type company. Participation: researcher.
2018-2019 – Characterization of novel molecular players in the control of obesity and obesity-induced inflammation. Agence des Universités Francophones. FAPESP. Responsible: Marcelo Hill, Carlos Escande, Alessandra Pontillo (USP).
