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职业迁徙
个人简介
My studies have been focused on developing approaches to target the tumor microenvironment and to unleash the power of the immune system against tumors. During my master thesis in Prof. Luigi Naldini's lab I developed a new gene therapy approach to selectively express the human Interferon-(IFN)-alpha transgene in the tumor infiltrating macrophage progeny of transplanted, genetically engineered hematopoietic stem progenitor cells (HSPC) and showed the safety, feasibility and efficacy of this strategy against mammary tumors (Escobar G., et al. Sci Trans Med 2014, cover story). My laboratory experience allowed me to acquire a broad spectrum of skills, to gain relevant experience on stem cell manipulation using retroviral system and to learn how to set up new in vivo tumor models (solid and hematological). My work published in 2014 on Science Translational Medicine set the scientific basis for the foundation of a start-up company named Genenta Science (http://www.genenta.com). During the same period, I contributed to show the efficacy of our IFN-gene therapy strategy in a colorectal cancer liver metastases model (Catarinella M, Monestiroli A., Escobar G. et al., EMBO Mol Med 2016). During my internship and PhD, I participated to the development of the first gene therapy strategy for the site-specific genome editing of human HSPC using artificial nucleases (Genovese P., Schiroli G*., Escobar G*. et al., Nature 2014). We achieved targeted genome editing in human HSPC and correction of HSPC from a patient with X-linked severe combined immunodeficiency. During my PhD training, I became interested in studying the immuno-modulatory effects of IFN-alpha gene therapy in hematologic tumors. Using a mouse B-lymphoblastic leukemia model I showed improved tumor clearance, T-cell responses against multiple tumor antigens and survival in IFN-treated mice. By performing single cell transcriptomic on tumor-infiltrating leukocytes, I uncovered IFN-mediated reprogramming of selected immune populations in responder IFN-treated mice and activation of immunosuppressive pathways in non-responder CTRL-treated mice (Escobar G. et al., Nature Communications 2018 ). As a result of these studies, I acquired significant knowledge on both basic and applied tumor immunology. During my 5 years of research activity, I proficiently and enthusiastically collaborated with members of the lab and the institute providing technical and scientific support, as testified by my co-authorship in five publications (Genovese et al., Nature 2014; Ronca R., Cancer Cell 2016; Catarinella M., EMBO Mol. Med. 2016; Mastaglio S., Blood 2017; Mucci A. EMBO Mol. Med. 2021).
For my post-doctoral training, I moved to Boston to join Ana C. Anderson’s laboratory at Brigham and Women’s Hospital and Harvard Medical School. During my early post-doctoral training I focused my research on studying how checkpoint blockade therapy affects the biology of T cells and proficiently contributed to a study where we characterized a population of stem-like TCF1+CD8+ T cells that is important for immune checkpoint blockade (ICB) therapy efficacy in mice and patients (Kurtulus*, Madi*, Escobar et al., Immunity 2019). Our work was selected as cover story by the journal Immunity for which I designed the cover concept. Following up on this work, I then made the important observation that the reliance on TCF1 in CD8 T cells for ICB efficacy depends on tumor immunogenicity. Using a conditional TCF1 KO model in CD8+ T cells I found that TCF1 is required for ICB efficacy in poorly, but not highly, immunogenic tumors. Specifically, TCF1 poises CD8+ T cells for optimal activation in suboptimal (i.e. low tumor antigen expression or low TCR affinity for cognate antigens) priming conditions, commonly found in tumors with low mutational burden. Importantly, defective TCF1 expression during tumor-specific CD8+ T cell activation resulted in the expansion of de-stabilized dysfunctional intra-tumoral CD8+ T cells that shared features with CD8+ T cells found in ICB non-responder patients (Escobar et al., Cancer Cell 2023, in press). Further, I collaborated with other members of the Anderson lab to investigate the molecular mechanisms by which tumors evade or suppresse immune responses (Nandini A.*, Madi A.*, et al, Immunity 2020; Tooley K*, Livnat Jerby-Arnon*, Escobar G., et al., in revision). I also contributed to two reviews on the role of the transcription factor TCF1 in T cells (Escobar*, Mangani* and AC Anderson, Science Immunology, 2020) and on the role of spatial determinants (soluble or cellular) in regulating CD8 T cell differentiation in cancer (Tooley K., Escobar G. and AC Anderson, Trends in Cancer, 2022). I am now committed to leverage my expertise in tumor immunology, in vivo tumor modelling and immune cell genetic engineering to modulate the immune system and develop better anti-cancer therapies.
研究兴趣
论文共 36 篇作者统计合作学者相似作者
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Katherine Tooley,Livnat Jerby,Giulia Escobar, S. Harsha Krovi,Davide Mangani, Gitanjali Dandekar,Hanning Cheng,Asaf Madi,Ella Goldschmidt,Conner Lambden,Rajesh K. Krishnan,Orit Rozenblatt-Rosen,Aviv Regev,Ana C. Anderson
Cell Reports Medicineno. 7 (2024): 101640
Cell researchno. 6 (2024): 399-400
Thais G. Moreira,Laura M. Cox, Patrick Da Silva,Davide Mangani,Marilia G. De Oliveira,Giulia Escobar,Toby B. Lanser, Liam Murphy,Eduardo.L.C. Lobo, Omer Milstein,Christian D. Gauthier, Ana Clara Guimarāes,Luke Schwerdtfeger, Mellicient N. Ekwudo,Caroline Wasén,Shirong Liu,Gustavo B. Menezes, Enio Ferreira,Galina Gabriely,Ana C. Anderson
Mucosal immunology (2024)
Giulia Escobar,Katherine Tooley, Joan Pagès Oliveras, Lüping Huang,Hanning Cheng,Chang Xue,Davide Mangani,Natanael Hazel,Carola Rutigliani,Luca Biasco,Ana C. Anderson
Cancer researchno. 7_Supplement (2023): 4157-4157
Regular and Young Investigator Award Abstracts (2022)
Cancer immunology researchno. 12_Supplement (2022): B35-B35
biorxiv(2021)
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作者统计
#Papers: 36
#Citation: 1629
H-Index: 11
G-Index: 16
Sociability: 5
Diversity: 2
Activity: 47
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