Experimental Gastroenterology Unit
The laboratory of Experimental Gastroenterology, headed by Federica Ungaro, is particulary interested in studying chronic inflammatory conditions in close collaboration with the hospital's clinical units.
THE MICROBIOME IN IBD
Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights also dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Our group aims at the full understanding of intestinal dysbiosis during IBD pathogenesis, with the promise of paving the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.
MACHINE LEARNING-DRIVEN IBD PATIENT STRATIFICATION
Currently available treatments for Inflammatory Bowel Disease (IBD), including ulcerative colitis and Crohn’s disease, although overall beneficial, may lose effectiveness so that some patients experience disease relapse. The main reason for these failures is that IBD is a complex disease, where numerous biological functions exert integrated and complementary roles. Also, IBD patients are highly heterogeneous, displaying different clinical and molecular characteristics. To overcome this limitation, we recently released the IBD Transcriptome and Metatranscriptome Meta-Analysis (TaMMA) framework, a comprehensive survey of all publicly available IBD RNA-Seq datasets, through which the disease complexity may be unraveled. Our group currently aims to perform a system-level understanding of IBD, where patients will be stratified based on their specific molecular, finally making possible the therapeutic target prioritization based on specific patient signatures, eventually paving the way to tailored therapies for IBD.
RESOLUTION OF INFLAMMATION IN COLORECTAL CANCER
The intrinsic connection between inflammation and tumor promotion is well characterized and is a key pathogenic event in patients with colorectal cancer (CRC). A small fraction of patients with CRC suffers from genetic predisposition, but environmental factors and chronic inflammation represent the major causes of intestinal carcinogenesis. Patients suffering from inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, have a high risk of developing colitis-associated CRC with poor prognoses. Whatever the cause, tumor-associated inflammation remains a crucial hallmark of CRC, where the co-occurrence of either intrinsic (cancer cells that trigger inflammation), or extrinsic (chronic inflammation that promotes cancer) processes promotes its development. Therefore, targeting cancer-associated inflammation may offer new avenues for cancer treatment. Anti-inflammatory drugs currently used for the treatment of patients with CRC show many adverse side effects that prompted researchers to propose the specialized pro-resolving mediators, derived from omega-3 polyunsaturated fatty acids, as promoters of resolution of cancer-associated inflammation. Considering the direct connection between inflammation and cancer development that mutually impact each other, our group is currently looking at new metabolic routes that can promote the resolution of inflammation in CRC, opening new horizons for the treatment of tumor-associated inflammation.
Massimino L., Spanò S., Lamparelli L.A., Fuggetta D., Peyrin-Biroulet L., Sileri P., Danese S., D’Alessio S. and Ungaro F&. Tofacitinib inhibits leukocyte trafficking across the intestinal endothelial barrier in a specific cohort of Ulcerative Colitis patients, Infl. Bowel Dis. (2021), IF 5.325, DOI: 10.1093/ibd/izab349 (PMID 35032171).
D’Alessio S.*, Ungaro F.*, Noviello D., Lovisa S., Peyrin-Biroulet L. & Danese S. Revisiting fibrosis in inflammatory bowel disease: the gut thickens, Nat Rev Gastroenterol Hepatol (2021). IF. 46.802 DOI: 10.1038/s41575-021-00543-0 (PMID: 34876680).
Massimino, L., Lamparelli, L.A., Houshyar, Y., D’Alessio S., Peyrin-Biroulet L., Vetrano S., Danese S. & Ungaro F&. The Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework. Nat Comput Sci 1, 511–515 (2021) DOI: 10.1038/s43588-021-00114-y (PMID not available yet).
Massimino L., Lovisa S., Lamparelli L.A., Danese S., Ungaro F&. Gut eukaryotic virome in colorectal carcinogenesis: Is that a trigger?, Computational and Structural Biotechnology Journal (2020) IF. 7.271 DOI: 10.1016/j.csbj.2020.11.055. (PMID: 33363706)
Ungaro F&, D'Alessio S, Danese S. The Role of Pro-Resolving Lipid Mediators in Colorectal Cancer-Associated Inflammation: Implications for Therapeutic Strategies. Cancers (2020) IF. 6.639 DOI: 10.3390/cancers12082060 (PMID: 32722560).
Ungaro F&, Massimino L, D'Alessio S, Danese S&. The gut virome in inflammatory bowel disease pathogenesis: From metagenomics to novel therapeutic approaches, United European Gastroenterol J (2019) IF. 4.623 DOI: 10.1177/2050640619876787. (PMID: 31662858).
Ungaro F, Garlatti V, Massimino L, Spinelli A, Carvello M, Sacchi M, Spanò S, Colasante G, Valassina N, Vetrano S, Malesci A, Peyrin-Biroulet L, Danese S, D'Alessio S. mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking Through Lymphatic Endothelium in Patients With Crohn's Disease, Cells (2019) IF. 4.829 DOI: 10.3390/cells8080924. (PMID: 31426584).
Tacconi C, Ungaro F, Correale C, Arena V, Massimino L, Detmar M, Spinelli A, Carvello M, Mazzone M, Oliveira A, Rubbino F, Garlatti V, Spanò S, Lugli E, Colombo F, Malesci A, Peyrin-Biroulet L, Vetrano S, Danese S, D'Alessio S, Activation of the VEGFC/VEGFR3 Pathway Induces Tumor Immune Escape in Colorectal Cancer, Cancer Research (2019) IF: 12.7 DOI: 10.1158/0008-5472.CAN-18-3657. (PMID: 31239267).
Ungaro F., Colombo P, Massimino L, Ugolini GS, Correale C, Rasponi M, Garlatti V, Rubbino F, Tacconi C, Spaggiari P, Spinelli A, Carvello M, Sacchi M, Spanò S, Vetrano S, Malesci A, Peyrin-Biroulet L, Danese S, D'Alessio S. Lymphatic endothelium contributes to colorectal cancer growth via the soluble matrisome component GDF11. Int. J. Cancer (2019) IF. 7.36 DOI: 10.1002/ijc.32286 (PMID: 30889293)
Ungaro F., Massimino L., Furfaro F., Rimoldi V., Peyrin-Biroulet L., D’Alessio S., and Danese S. Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease, Gut Microbes (2018) IF 10.245 DOI: 10.1080/19490976.2018.1511664. (PMID: 30252582)
Ungaro F., Rubbino F., Danese S., D’Alessio S. Actors and Factors in the Resolution of Intestinal Inflammation: Lipid Mediators As a New Approach to Therapy in Inflammatory Bowel Diseases. Front Immunol. (2017) IF 10.245 DOI: 10.3389/fimmu.2017.01331. (PMID: 29109724).
Ungaro F., Tacconi C., Massimino L., Corsetto P.A., Correale C., Fonteyne P., Piontini A., Garzarelli V., Calcaterra F., Della Bella S., Spinelli A., Carvello M., Rizzo A.M., Vetrano S., Petti L., Fiorino G., Furfaro F., Mavilio D., Maddipati K.R., Malesci A., Peyrin-Biroulet L., D'Alessio S., Danese S. MFSD2A Promotes Endothelial Generation of Inflammation- Resolving Lipid Mediators and Reduces Colitis in Mice. Gastroenterology (2017) IF 22.68 DOI: 10.1053/j.gastro.2017.07.048. (PMID: 28827082).