Experimental oncology
Lymphoid organ development
Our research focuses on the biology of nonhematopoietic stromal cells of lymphoid tissues. Stromal cells are emerging as critical organizers of the lymphoid microenvironment, and regulators of tissue homeostasis in health and disease, such as cancer.
Research activity
By combining genetic, molecular and imaging approaches coupled to in vitro 3D culture systems, we aim to decipher how stromal cells:
- construct the lymphoid microenvironment during embryonic and postnatal development,
- support survival and progression of hematological and solid tumors,
- promote tissue remodeling and disease spreading during cancer evolution.
We are also actively translating basic principles of lymphoid organogenesis into development of articial lymphoid organs for pre-clinical applications in cancer and regenerative medicine.
Farinello D, Wozińska M, Lenti E, Genovese L, Bianchessi S, Migliori E, Sacchetti N, di Lillo A , Bertilaccio MTS, de Lalla C, V alsecchi R, Gleave SB, Lligé D, Scielzo C, Mauri L, Ciampa MG, Scarfò L, Bernardi R, Lazarevic D, Gonzalez - Farre B, Bongiovanni L, Campo E, Cerutti A, Ponzoni M, Pattini L, Caligaris - Cappio F, Ghia P, Brendolan A. A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression. 2018. Nature Commun, 3;9:1787
Sanarico AG, Ronchini C, Croce A, Memmi EM, Cammarata UA, De Antoni A, Lavorgna S, Divona M, Giacò L, Melloni G, Brendolan A, Simonetti G, Martinelli G, Mancuso P, Bertolini F, Lo-Coco F, Melino G, Pelicci PG and F Bernassola. The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukemia. Leukemia 2018 Apr;32(4):911-919.
Golub R, Tan J, Watanabe T, and A. Brendolan. Origin and immunological functions of spleen stromal cells. Trends in Immunology 2018 Mar 19. pii: S1471-4906(18)30043-7.
Lenti E, Farinello D, Castagnaro D, Nederreither K, Lavorgna G, Tonon G, Blasi and A. Brendolan. TLX1 controls retinoic acid signaling to ensure spleen development. Journal of Clinical Investigation 2016 Jul 1;126(7):2452-64.
Valsecchi R, Coltella N, Belloni D, Ponente M, Ten Hacken E, Scielzo C, Scarfò L, Bertilaccio MT, Brambilla P, Lenti E, Martinelli Boneschi F, Brendolan A, Ferrero E, Ferrarini M, Ghia P, Tonon G, Ponzoni M, Caligaris Cappio F, Bernardi R. HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment. Blood 2016 Apr 21;127(16):1987-97.
Genovese L, Brendolan A. Lymphoid tissue mesenchymal stromal cells in development and tissue remodeling. Stem Cell International 2016;2016:8419104.
Castagnaro L, Lenti E, Maruzzelli S, Spinardi L, Migliori E, Farinello D, Sitia G, Harrelson Z, Evans SM, Guidotti LG, Harvey RP, Brendolan A. Nkx2.5/Islet1+ spleen mesenchymal progenitors generate different stromal cell lineages and participate in organ regeneration. Immunity 2013 Apr 18;38(4):782-91.
Penkov D, Mateos San Martín D, Fernandez-Díaz LC, Rosselló CA, Torroja C, Sánchez-Cabo F, Warnatz HJ, Sultan M, Yaspo ML, Gabrieli A, Tkachuk V, Brendolan A, Blasi F, Torres M. Analysis of the DNA-binding profile and function of TALE homeoproteins reveals their specialization and specific interactions with Hox genes/proteins. Cell Reports 2013 Apr 25;3(4):1321-33.
Koss M, Bolze A*, Brendolan A*, Saggese M, Capellini TD, Bojilova E, Boisson B, Prall OW, Elliott DA, Solloway M, Lenti E, Hidaka C, Chang CP, Mahlaoui N, Harvey RP, Casanova JL, Selleri L. Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module. Developmental Cell 2012 May 15;22(5):913-26. (*equal contribution).
Brendolan A, Caamano JH. Mesenchymal cell differentiation during lymph node organogenesis. Frontiers in Immunology 2012 Dec 14;3:381.
