Andrea Brendolan
Andrea Brendolan
e-mail:
affiliation: San Raffaele Scientific Institute
research area(s): Developmental Biology, Immunity And Infection
Course: Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
Education
1995 B.S Pharmacology, University of Modena, Italy
2005 Ph.D Experimental Medicine, University of Modena, Italy

Professional experiences/appointments
1997-1998 Research Fellow, Division of Immunology, University of Verona Medical School, Italy.
1998-2001 Research Fellow, Division of Immunology, Stanford University, Stanford, CA.
2001-2007 Research Associate, Depart. Cell and Dev Biology, Cornell Medical Center, New York, NY.
2007: Visiting Scientist, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
2008-present: Group Leader, Laboratory of Lymphoid Organ Development and Function, San Raffaele Scientific Institute, Milan, Italy.
Our research program seeks to understand the development and function of lymphoid organ microenvironment. Specifically, the long term goals are: 1) to comprehend the molecular mechanisms by which oncogenic transcription factors regulate genetic and transcriptional programs during lymphoid organogenesis; 2) to uncover the ontogeny and differentiation pathways of stromal cell subsets within lymphoid organs and their role is supporting immune responses during normal and pathological conditions; 3) to dissect the in vivo functions of stromal cell subsets in supporting normal and neoplastic cell growth; 4) to construct functional and transplantable artificial lymphoid organs as a novel approach to enhance anti-tumor immunity.

1. Chung EY, Liu J, Homma Y, Zhang Y, Brendolan A, Maggese M, Han, R. Silverstein J, Selleri L, Ma X. Interleukin-10 expression in macrophages during phagocytosis of apoptotic cells is mediated by the homeodomain proteins Pbx1 and Prep1. Immunity 2007; 27: 952-964.

2. Brendolan A, Rosado M, Carsetti R, Selleri L and Dear TN. Development and function of the mammalian spleen. Bioessay 2007; 29: 166-77.

3. Zhang X, Heaney S, Rowan S, Yue Y, Brendolan A, Selleri L, Maas RL. Pax6 is regulated by Meis and Pbx homeoproteins during pancreatic development. Dev Biology 2006; 300: 748-57.

4. Capellini T, Di Giacomo G, Salsi V, Brendolan A, Ferretti E, Srivastava D, Zappavigna V, Selleri L. Pbx1/Pbx2 requirement for distal limb patterning is mediated via the hierarchical control of Hox and Shh expression. Development 2006; 133: 2263-73.

5. Brendolan A, Ferretti E, Salsi V, Moses K, Quaggi├╣ S, Blasi F, Cleary ML, Selleri L. A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Development 2005; 132: 3113-26.
Project Title:
Development and function of artificial lymphoid organs
Secondary lymphoid organs, such as spleen and lymph nodes, are thought to serve
as focal regions supporting and facilitating cell-cell interactions required for
generating adaptive immune responses. Synthesis of artificial lymphoid tissues is
an emerging field that aims to provide therapeutic application for the treatment of
severe infection, cancer, and age-related involution of secondary lymphoid tissues.
We have recently succeeded in constructing artificial lymphoid organs (aLOs) by
using primary embryonic mesenchymal cells as a source of stromal progenitors and
found that they efficiently support lymphoid architecture in vivo. In addition to
primary progenitors, the fist goal of the research project is to exploit induced
pluripotent stem (iPS) cells (already available in our laboratory) as a possible
source of lymphoid stromal progenitors for the construction of functional artificial lymphoid organs. iPS cells expressing YFP under the control of stroma-specific genes will be used to derive stromal progenitors by activated cell sorting and tested for in vivo capacity to generate artificial lymphoid structures. The second goal of the research project is to exploit transplantable aLOs loaded with tumor antigens to generate long-lasting anti-tumor immunity in a mouse model melanoma.

References:
1) Irvine et al. Lymphoid tissue engineering: invoking lymphoid tissue neogenesis
in immunotherapy and models of immunity. Semin Immunol. 2008
Apr;20(2):137-46.
2) Suematsu and Watanabe. Generation of a synthetic lymphoid tissue-like
organoid in mice. Nat Biotechnol. 2004 Dec;22(12):1539-45.
3) Tan JK, Watanabe T. Artificial engineering of secondary lymphoid organs.
Adv Immunol. 2010;105:131-57.


Project Title:
Role of lymphoid organ stromal cells in blood cancer development
Blood cancer development and progression depends on a complex interplay of cell-cell interactions and signaling molecules occurring between neoplastic cells and their surrounding stromal microenvironment. However, the mechanisms by which stromal cells contribute to survival and expansion of neoplastic cells are still far to be elucidated. To this end, we have developed an in vivo strategy to permanently label stromal cells of lymphoid organs with yellow fluorescent protein. This allow us to follow their interactions with neoplastic cells in murine models of chronic lymphocytic leukemia and multiple myeloma.
The goal of the research project is to exploit this strategy to isolate stromal cell subsets at different stages of disease progression and determine the evolution (e.g. gene expression profile) of the stromal microenvironment during the course of tumor development. Candidate stromal signatures identified by DNA-microarray technology will be validated in vivo in mouse models and in vitro by using a cell culture system based on lympho-stromal interactions. In addition, by using in vivo confocal analysis we intend to characterize the dissemination of neoplastic cells and identifies specific niches of stromal cells that promote
survival and growth of leukemia/myeloma cells. We expect to shed light on the
mechanisms by which the tumor microenvironment sustains tumor development and progression.

References:
1) Dierks et al. Essential role of stromally induced hedgehog signaling in B-cell
malignancies. Nat Med. 2007 Aug;13(8):944-51.
2) Rehm et al. Cooperative function of CCR7 and lymphotoxin in the formation of a
lymphoma-permissive niche within murine secondary lymphoid organs. Blood. 2011 May
17.