Contact Information
- AddressVia Rita Levi Montalcini, 4 - 20090 Pieve Emanuele (Milano) Italy
- Telephone+39 02 8224 7231
- Fax+39 02 8224 2298
- E-mailana.lleo@humanitas.it
We are a multidisciplinary team focused on projects of translational nature in liver tumors and, more broadly, in liver diseases. Our research is focused on the liver environment and the molecular mechanisms determining tumor development and progression; including cellular immunology, genetics, and metabolomics of both primary and metastatic liver cancer. Our efforts are aimed at translating knowledge from bench to bedside; our final goal is to identify prognostic predictors and molecular targets, and to facilitate their implementation into the clinical management of patients. The Lab of Hepatobiliary Immunopathology works in close relationship with the Unit of Hepatobiliary Surgery (directed by Prof. G Torzilli) and the Unit of Hepatology (directed by Prof A Aghemo).
Active ongoing projects:
1. Characterization and pathogenic role of hepatic macrophages in Colorectal Liver Metastases
Liver resection combined with systemic chemotherapy has been recognized as the potentially curative treatment for patients with colorectal cancer liver metastases. However, some patients undergoing liver resection do not have long-term survival. Therefore, additional markers to understand the biological dynamics of the disease after hepatectomy are needed. Tumor-associated macrophages and Myeloid-Derived Suppressor Cells (MDSC) are emerging as attractive targets because increasing evidence has demonstrated that their accumulation is related to poor prognosis and drug resistance. Furthermore, the immunohistochemistry analysis of peritumoral macrophages in patients has shown a strong correlation between the percentage of macrophages and the aggressiveness of the metastases
2. Decoding the clinical heterogeneity and therapeutic resistance of intrahepatic cholangiocarcinoma
Cholangiocarcinoma is the second primary liver malignancy in terms of frequency. There are few data regarding the molecular pathogenesis and signaling cascades implicated in this tumor. This project aims to dissect the genetic, phenotypic, and metabolomic characteristic of neoplastic cholangiocytes and the tumor associated immune infiltrate. In addition, we aim at identifying novel molecular targets susceptible to selective blockade, followed by their experimental validation.
3. Cholangiocytes-on-a-chip: a platform to identify medical therapy
Disruption of the hepatobiliary homeostasis leads to altered cellular signaling, immune system activation, inflammation, and eventually liver fibrosis. Due to the complexity of the in vivo cellular interactions, these mechanisms are largely unknown and therapeutic strategies are limited. In a collaboration with the Politecnico di Milano, we aim at developing and employing a clinical in vitro tool based on microfluidic 3D multi-cell culture that will help in deciphering the pathological contribution of each cellular actor as well as in screening drug efficacy with a personalized patient approach.
These projects are currently supported by the Fondazione AIRC per la Ricerca sul Cancro, COST-Action (Horizon 2020), Regione Lombardia, and the Italian Ministry of Health.
If you are interested in a research position, please send a motivation letter, your CV, and the contact information (or letters of recommendation) of at least two referees to Prof Ana Lleo
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Ana Lleo Publications
Selected Publications: 20-25 publications listed in details with all the contributing authors, title of the papers, journal, dates. Donadon M, Lleo A, Di Tommaso L, Soldani C, Franceschini B, Roncalli ...
