Genomics of the innate immune system
Theis group employs a multidisciplinary approach that combines high-throughput and single-cell genomics, genome engineering and functional studies to dissect the principles of immune cell development and functions. Building on relevant mouse models and uniquely available clinical samples, the aim is to decipher the complex networks of signaling pathways, transcription factors (TF), chromatin regulators and non-coding RNAs that control gene expression in the innate immune system.
- Homeostatic and stress-induced development of the human innate immune system. In this project, the group uses cutting-edge genomics and single-cell transcriptomics technologies to explore stress-induced human myelopoiesis in sets of clinical samples collected longitudinally throughout allogeneic hematopoietic stem cell (HSC) and BM transplantation procedures. This research will uncover the cellular and molecular mechanisms of immune reconstitutions after chemotherapy, with direct implications for HSC gene therapy and treatment of hematological malignancies.
- Genomic and transcriptional control of tumor-associated macrophages. The group aims to dissect how macrophage functions are affected by complex combination of environmental stimuli during homeostasis and disease, with a focus on cancer. Tumor-associated macrophages (TAM) frequently display a “mixed” polarization state characterized by concomitant pro- and anti- inflammatory activities that support, rather than suppress, tumor growth. In the lab, the aim is to define the phenotype and functions of TAM, and to develop innovative cell and gene therapy strategies to therapeutically reprogram macrophage activities.
Piccolo V, Curina A, Genua M, Ghisletti S, Simonatto M, Sabò A, Amati B, Ostuni R*, Natoli G*. Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk. Nature Immunology 2017 May;18(5):530-540. *Co-last and corresponding author.
Sammicheli S, Kuka M, Di Lucia P, de Oya NJ, De Giovanni M, Fioravanti J, Cristofani C, Maganuco CG, Fallet B, Ganzer L, Sironi L, Mainetti M, Ostuni R, Larimore K, Greenberg PD, de la Torre JC, Guidotti LG, Iannacone M. Inflammatory monocytes hinder antiviral B cell responses. Science Immunology 2016 Oct 21;1(4). pii: eaah6789.
Ostuni R*, Natoli G, Cassatella MA, Tamassia N*. Epigenetic regulation of neutrophil development and function. Seminars in Immunology 2016 Apr;28(2):83-93. *Co-last and corresponding author.
Ostuni R*, Kratochvill F, Murray PJ, Natoli G*. Macrophages and cancer: from mechanisms to therapeutic implications. Trends in Immunology. 2015 Apr;36(4):229-39. *Co-corresponding author.
Zimmermann M, Aguilera FB, Castellucci M, Rossato M, Costa S, Lunardi C, Ostuni R, Girolomoni G, Natoli G, Bazzoni F, Tamassia N, Cassatella MA. Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils. Nature Communications. 2015 Jan 23;6:6061.
Ostuni R*, Piccolo V, Barozzi I, Polletti S, Termanini A, Bonifacio S, Curina A, Prosperini E, Ghisletti S, Natoli G*. Latent enhancers activated by stimulation in differentiated cells. Cell 2013 Jan 17;152(1-2):157-71. Highlights in Nature Reviews Genetics, Nature Immunology, F1000 (13 stars). *Co-corresponding author.
Zanoni I*, Ostuni R*, Barresi S, Di Gioia M, Broggi A, Costa B, Marzi R, Granucci F. CD14 and NFAT mediate lipopolysaccharide-induced skin edema formation in mice. Journal of Clinical Investigations 2012 May;122(5):1747-57.*Co-first author.
Austenaa L, Barozzi I, Chronowska A, Termanini A, Ostuni R, Prosperini E, Stewart AF, Testa G, Natoli G. The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis. Immunity. 2012 Apr 20;36(4):572-85.
Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC. CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. Cell. 2011 Nov 11;147(4):868-80. Highlights in F1000 (2 stars).
Zanoni I, Ostuni R, Capuano G, Collini M, Caccia M, Ronchi AE, Rocchetti M, Mingozzi F, Foti M, Chirico G, Costa B, Zaza A, Ricciardi-Castagnoli P, Granucci F. CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation. Nature. 2009 Jul 9;460(7252):264-8. Highlights in F1000 (2 stars).