Profiles

I am an immunologist with 23 years of research experience, and also hold a degree in bioinformatics. I investigate the mechanisms regulating adaptive immune responses as well as the basis for their inappropriate function in autoimmune diseases and cancer.
My area of excellence is investigation of the mechanisms that regulate the immune response. During my graduate studies with Prof. Roncarolo (San Raffaele - Milano) I studied T cell dysfunction in Wiskott-Aldrich syndrome and its correction after lentiviral vector-mediated gene therapy, generating key data in support of a clinical trial that so far has cured 17 children. My post-doctoral work with Thorsten Mempel (Massachusetts General Hospital) revolves around the question of how interactions between T and antigen-presenting cells in cancer drives its rejection or progression. I approached this question by directly visualizing NFAT signaling within cancer-associated T cells using multiphoton intravital microscopy (MP-IVM). I demonstrated that NFAT activity persisting beyond the duration of interactions with APC promotes T cell tolerance in CD8+ T cells, yet surprisingly boost the function of T regulatory cells within the tumor tissue. The mechanisms driving these divergent functions downstream comparable dynamics of activation will be a fertile area of investigation.
I published 34 manuscripts in journals such as Immunity, Cancer Cell, Cell, Science and Nature, 8 as lead and 5 as corresponding author. My studies have also been vital in implementing one clinical trial for Wiskott-Aldrich Syndrome. I trained 19 lab members, 17 of whom made important scientific contributions to my projects and are co-authors of my manuscripts. All my current graduate students received very competitive funding (including one NIH F31, and two NSF-GRFP).
I have established my independent lab at the end of 2019. We aim to study the innate and adaptive immune mechanisms promoting tolerance to cancer. The focus of the “innate immunity” branch of my lab is to investigate how fully differentiated macrophages dynamically switch in vivo from promoting to opposing inflammation and vice versa, with the ultimate goal of instructing functions that ameliorate the outcome of neoplastic diseases. This approach holds so much promise that its achievement has been defined the “Holy Grail” of macrophage therapeutic targeting (Sica J Clin Invest 2012). I plan to systematically address this scientific problem using novel transgenic mice to map the functional fate of pro-inflammatory macrophages, in combination with intravital microscopy. The “adaptive immunity” branch of my lab studies the effects of checkpoint blockade immunotherapy on T regulatory cells (Tregs). We found that CTLA-4 blockade leads to the accumulation of tumor-associated Tregs, in turn worsening the therapeutic outcome (Marangoni Cell 2021). More recently, my group found that PD-1 immunotherapy increases the abundance of Tregs in the melanoma microenvironment because of a previously unrecognized “help” by IL-2-producing CD8 T cells (Geels et al., Cancer Cell 2024). The translation of the basic concepts we identified to anti-tumor therapies will be a crucial focus for the future.