Assistant Professor, Physiology & Biophysics
School of Medicine
Ph.D., Vita-Salute San Raffaele University, Milano, Italy, 2007, Molecular Medicine - Basic and Applied Immunology
M.S., University of Torino, Italy, 2003, Bioinformatics
M.S., University of Bologna, Italy, 2001, Medical Biotechnology
University of California, Irvine
3034 Hewitt Hall
Mail Code: 4560
Irvine, CA 92697
Immune Regulation, Cancer Immunology, Functional Intravital Imaging, Regulatory T cells, Macrophages
2019: "Nancy Tarbell" Fellowship (Harvard Medical School).
2013: “Sara Elizabeth O’Brien” Fellowship (Charles King Trust).
2009: "Fund for Medical Discovery" Fellowship (Massachusetts General Hospital).
2005-2013: Recipient of 7 distinct Best Poster Awards or Travel Grants at International Congresses.
2003: Graduate student fellowship, Vita-Salute San Raffaele University, Milan, Italy.
2001: “M. Oblach” prize for best thesis in experimental oncology at the University of Bologna, Italy.
2001: Fellowship to attend the Master Course in Bioinformatics, University of Turin, Italy.
Our immune system is effective in protecting us against pathogens, yet its activity has to be finely regulated in order to avoid collateral damage to ourselves. My lab is devoted to study these immunoregulatory mechanisms because they are often deranged in disease: they are insufficiently activated in autoimmunity and exuberant in cancer. Our long-term mission is to understand immunoregulatory mechanisms and manipulate them as a new form of immunotherapy for autoimmune and neoplastic diseases.
Our main technological approach is functional intravital imaging (F-IVM). We use fluorescent probes of key biological processes (e.g. T and B cell activation; macrophage inflammatory potential) to directly visualize how they unfold during an immune response in living mice.
We are currently pursuing these two lines of research:
IMPACT OF CHECKPOINT BLOCKADE ON THE ACTIVATION OF TUMOR-ASSOCIATED REGULATORY T CELLS.
By using F-IVM, we discovered that tumor-associated regulatory T cells (Treg) are constantly activated within the tumor mass by repetitive short-lived interactions with APC. Because tumor-associated Treg express high amounts of PD-1, it is possible that cancer immunotherapy by PD-1 blockade further increases Treg activation within cancer, which is unwanted as it may reduce the efficacy of immunotherapy. We will investigate this hypothesis by visualizing Treg activation in vivo through F-IVM, and hopefully use the resulting knowledge to suggest ways to improve the efficacy of PD-1 blockade in oncologic patients.
MECHANISMS OF MACROPHAGE FUNCTIONAL SWITCH IN WOUND HEALING AND MELANOMA.
Macrophages are fascinating cells in that have a marked functional plasticity: they are able to become pro- or anti-inflammatory depending on the environmental cues they sense. During wound closure, switch from pro- to anti-inflammatory functions is a desired process that helps healing, yet this is not at all the case in cancer, where pro-inflammatory macrophages are forced to become anti-inflammatory and to support tissue regeneration, critically contributing to tumor progression. In this project we will create new mouse models in which macrophage plasticity from pro - to anti-inflammatory functions and vice-versa can be directly visualized by F-IVM. We will study the cellular contacts and the molecular determinants that are key for macrophages to keep, or gain pro-inflammatory functions, and once these are known, we will exploit them to induce immunological rejection of tumors. This project is financed by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS).
Full list of publications at: https://orcid.org/0000-0002-2490-849X
NIH-NIAMS 1R21AR072849-01A1 “Mechanisms of Macrophage Functional Switch during Skin Repair”
P30 Skin Seed Grant “Interactions between skin and the immune system in health and disease”
American Association of Immunologists
Cellular and Molecular Biosciences
Mathematical and Computational Biology
Medical Scientist Training Program
Institute for Immunology
Chao Family Comprehensive Cancer Center
Cancer Research Institute of the UCI