Genetics and cell biology
Emanuel Della Torre
Email: dellatorre.emanuel@hsr.it
Location: DIBIT1 A3, Floor 4, Room 37A-54
Project Leader, Translational Immunology Unit
Emanuel Della Torre obtained his Medical Degree (2008) and Board Certification in Allergy and Clinical Immunology (2014) at Università Vita-Salute San Raffaele.
He received his PhD in Basic and Applied Immunology at Università Vita- Salute San Raffaele in the lab of Prof. Angelo Manfredi investigating the role of B-lymphocytes in the pathogenesis of IgG4-related disease, an emerging fibro-inflammatory immune-mediated condition. During these years he uncovered B-cell subsets with overlooked fibrotic properties that contribute to the physiological resolution of tissue inflammation as well as to the pathological collagen deposition observed in a number of fibrosing disorders such as systemic sclerosis.
In 2016 Emanuel joined the laboratory of Prof. Shiv Pillai at the “Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard” in Boston (MA, USA) as a post-doctoral fellow. In 2019 he returned to San Raffaele Hospital and established his lab within the Division of Genetic and Cell Biology.
Emanuel Della Torre is now Assistant Professor of Rheumatology at Vita-Salute San Raffaele University and Senior Consultant at the Unit of Immunology, Rheumatology, Allergy, and Rare Disease (UnIRAR) of San Raffaele Hospital. He authored more than 100 scientific publications on international peer-reviewed journals and was awarded by national and international funding agencies such as the Collegio Ghislieri (2014) and the Cariplo Foundation (2018) awards for young researchers, the TRIDEO (2014) and the MyFirst (2021) research grants from Associazione Italiana Ricerca sul Cancro (AIRC), the Career Research Grant from the FOREUM Foundation (2020), the Ricerca Finalizzata (RF) (2021) and the Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN) (2022) research grants from the Italian Ministry of Health, University and Research.
Research activity
Dual aim of the research activity conducted in the lab is (i) to address the pathophysiology of rare immune-mediated diseases, and (ii) to translate original observations to the field of medical immuno-rheumatology and oncology. This is pursued through a translational model that integrates clinical observations and basic science in a “bedside-to-bench-to-bedside” approach.
In particular, thanks to strong collaborative ties with the Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) and with the Pancreas Translational & Clinical Research Center of San Raffaele Hospital our research is focused on IgG4-Related Disease (IgG4-RD) (an emerging fibro-inflammatory condition) and on Pancreatic Adenocarcinoma (PDAC) (one of the deadliest solid tumors). Similarities in the immune-cell infiltrate and activation of the stromal compartment between these two conditions suggest common mechanisms of interaction between B-lymphocytes and fibroblasts ultimately leading to the typical fibrotic outcome observed in both IgG4-RD and PDAC. We have indeed demonstrated that plasmablasts and plasma cells (but not naïve or memory B-cells) bear a pro-fibrotic machinery that enable them to interact with fibroblasts and to regulate the stiffness of the extracellular matrix. These cells are expanded in the blood and tissue of patients with IgG4-RD and PDAC and actively participate in stromal activation. Our discovery paves the way for using B-cell depleting therapies to target exuberant tissue fibrosis in IgG4-RD and other immune-mediated disorders with fibrotic outcomes, and provides a rationale for exploring their utility to hamper stromal hyperplasia in PDAC.
Projects funded by Associazione Italiana Ricerca sul Cancro and by the Italian Ministry of Health are ongoing in the lab to investigate the genetic background and the role of IgG subclasses in the pathogenesis of IgG4-RD in order to instruct further research paths for PDAC and to design personalized therapies for IgG4-RD patients.
Lanzillotta M, Culver E, Sharma A, Zen Y, Zhang W, Stone JH, Della-Torre E. Fibrotic phenotype of IgG4-related disease. Lancet Rheumatol. 2024
Della-Torre E, Criscuolo E, Lanzillotta M, Locatelli M, Clementi N, Mancini N, Dagna L; COVID-BioB study group. IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19. Lancet Rheumatol. 2021 Dec;3(12):e829-e831.
Rovati L, Kaneko N, Pedica F, Monno A, Maehara T, Perugino C, Lanzillotta M, Pecetta S, Stone JH, Doglioni C, Manfredi AA, Pillai S, Della-Torre E. Mer tyrosine kinase as a possible link between resolution of inflammation and tissue fibrosis in IgG4-related disease. Rheumatology (Oxford). 2021 Oct 2;60(10):4929-4941.
Minici C, Rigamonti E, Lanzillotta M, Monno A, Rovati L, Maehara T, Kaneko N, Deshpande V, Protti MP, De Monte L, Scielzo C, Crippa S, Arcidiacono PG, Dugnani E, Piemonti L, Falconi M, Pillai S, Manfredi AA, Della-Torre E. B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma. Oncoimmunology. 2020 Jul 16;9(1):1794359.
Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4 related disease. British Medical Journal. 2020 Jun 16;369:m1067.
Della-Torre E, Rigamonti E, Perugino C, Baghai-Sain S, Sun N, Kaneko N, Maehara T, Rovati L, Ponzoni M, Milani R, Lanzillotta M, Mahajan V, Mattoo H, Molineris I, Deshpande V, Stone JH, Falconi M, Manfredi AA, Pillai S. B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease. J Allergy Clin Immunol. 2020 Mar;145(3):968-981.e14.
Della-Torre E, Bozzalla-Cassione E, Sciorati C, Ruggiero E, Lanzillotta M, Bonfiglio S, Mattoo H, Perugino CA, Bozzolo E, Rovati L, Arcidiacono PG, Balzano G, Lazarevic D, Bonini C, Falconi M, Stone JH, Dagna L, Pillai S, Manfredi AA. A CD8- Subset of CD4+ SLAMF7+ Cytotoxic T Cells is Expanded in Patients with IgG4-Related Disease and Decreases following Glucocorticoid Treatment. Arthritis Rheumatol. 2018 Mar 2. doi: 10.1002/art.40469.
Della-Torre E, Feeney E, Deshpande V, Mattoo H, Mahajan V, Kulikova M, Wallace ZS, Carruthers M, Chung RT, Pillai S. B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease. Stone JH. Ann Rheum Dis. 2015 Dec;74:2236-43.