BIOGRAPHICAL SKETCH of FRANCESCA DI ROSA Senior

BIOGRAPHICAL SKETCH of FRANCESCA DI ROSA
POSITION TITLE
Senior Staff Scientist (Primo Ricercatore CNR)
at the Institute of Molecular Biology and Pathology, now Institute of Biology, Molecular Medicine and
NanoBiotechnologies, Italian National Research Council (CNR), c/o University of Rome Sapienza, Italy
EDUCATION/TRAINING
INSTITUTION AND LOCATION
DEGREE
YEAR
University of Naples Federico II, Naples, Italy
(Supervisor of M.D. thesis: Serafino Zappacosta)
M.D.
1990
Medicine
Ph. D.
1995
Cellular and Molecular
Biology and Pathology
Postdoctoral
1993-1995
Postdoctoral
1996-2001
University of Naples Federico II, Naples, Italy
(Supervisor: Serafino Zappacosta)
National Institutes of Health, Bethesda, MD, USA
(Supervisor: Polly Matzinger)
University of Rome La Sapienza, Rome, Italy
(Supervisors: Vincenzo Barnaba 1996-1998;
Angela Santoni 1999-2001 )
FIELD OF STUDY
Immunology
Immunology
A. Personal Statement
Most of my research activity has dealt with the mechanisms controlling the induction and maintenance
of T lymphocyte antigen-specific response, with a special interest in CD8 T cells. I worked on the
characterization of the helper signal necessary for CD8 T cell priming. This signal is provided by the helper
CD4 T cells through a conditioning of the DC and can be mimicked by a cross-linking of the DC membrane
molecule CD40, or by a virus infection of the DC. Since my PhD studies, I have been particularly interested in
the mechanisms underlying the maintenance of CD8 T cell memory. I studied the CD8 T cell memory response
to the male antigen H-Y in mice deficient in CD4 T cells or B cells and found that memory in these mice was
virtually unimpaired. These results suggest that the stimuli involved in CD8 T cell activation may be different
from those that maintain memory, and that there is no requirement for long-term retention of immune
complexes, nor for B cells as APC to maintain CD8 T cell memory
More recently, I formulated the hypothesis that the capacity of CD8 T cells to migrate to the bone
marrow (BM) and assume long-term residence in this site may be an important aspect of immunological
memory. I observed that a distinct set of molecules regulates T cell homing to either BM or lymph nodes, and
that T cell entry into the BM is a competitive process among T cells. Not only BM memory CD8 T cells are
more responsive to the antigen than their splenic counterparts, but they actually have a higher rate of local
proliferation. I observed such increased proliferation in the BM in the case of vaccine-primed antigen-specific
memory CD8 T cells, long time after immunization, as well as in the case of memory-phenotype CD44high
CD8 T cells in untreated mice. My findings and those from other labs (reviewed in Di Rosa, 2009) have several
implicatios for the induction and maintenance of effective CD8 T cell immunity, both in the context of
vaccination (e.g. memory CD8 T cell seeding of the BM is linked to long-term systemic memory) and in that of
tolerance (e.g. memory CD8 T cells are stimulated and proliferate in the BM, but they don’t normally give
autoimmune reactions). Moreover, the BM can be an excellent source of effector CD8 T cells for adoptive
immuno-therapy of both haematological malignancies and solid cancers.
B. Positions and Honors
Positions and Employment
2001-2007
Permanent Staff Scientist (Ricercatore CNR) at the Institute of Genetics and Biophysics
“Adriano Buzzati Traverso”, Italian National Research Council (CNR), Naples, Italy
2007-present Permanent Senior Staff Scientist (Primo Ricercatore CNR) at the Institute of Molecular Biology
and Pathology, now Institute of Biology, Molecular Medicine and NanoBiotechnologies, Italian National
Research Council (CNR), Rome, Italy
Qualifications (waiting to be hired in the new position)
2010- Associate Professor of General Pathology / Immunology, University of Rome 3 (idoneità, till 2015)
2014- Associate Professor of General Pathology / Immunology, National Competition (abilitazione, till 2018)
Other Experience and Professional Memberships
1990-present
Member, Italian Society of Immunology, Clinical Immunology and Allergology, SIICA;
1991-present
Member, Ruggero Ceppellini Advanced School of Immunology founded by Serafino
Zappacosta
2001-2004
Board of Directors, Ruggero Ceppellini Advanced School of Immunology
C. Selected Peer-reviewed Publications (Selected from 21 peer-reviewed publications)
1. F. Di Rosa & P. Matzinger. Long-lasting CD8 T cell memory in the absence of CD4 T cells or B cells. J Exp
Med 183: 2153-2163, 1996.
2. J. P. Ridge, F. Di Rosa & P. Matzinger. A conditioned dendritic cell can be a temporal bridge between a
CD4+ T helper and a T killer cell. Nature 393: 474-478, 1998.
3. F. Di Rosa, S. Ramaswamy, J. P. Ridge & P. Matzinger. On the lifespan of virgin T lymphocytes. J Immunol
163: 1253-1257, 1999.
4. F. Di Rosa, & A. Santoni. Bone marrow CD8 T cells are in a different activation state than those in lymphoid
periphery. Eur J Immunol 32: 1873-1880, 2002.
5. E. Parretta, G. Cassese, P. Barba, A. Santoni, J. Guardiola, & F. Di Rosa. CD8 cell division maintaining
cytotoxic memory occurs predominantly in the bone marrow. J Immunol 174: 7654-7664, 2005.
6. F. Di Rosa & R. Pabst. The bone marrow: a nest for migratory memory T cells. Trends Immunol 26: 360366, 2005.
7. G. Cassese, E. Parretta, L. Pisapia, A. Santoni, J. Guardiola & F. Di Rosa.Bone marrow CD8 cells downmodulate membrane IL-7Rα expression and exhibit increased STAT-5 and p38 MAPK phosphorylation in the
organ environment. Blood. 110: 1960-1969. 2007.
8. E. Parretta, G. Cassese, A. Santoni, J. Guardiola. A. Vecchio & F. Di Rosa. Kinetics of in vivo proliferation
and death of memory and naive CD8 cells: parameter estimation based on BrdU incorporation in spleen, lymph
nodes and bone marrow.J Immunol 180: 7230-7239. 2008.
9. F. Di Rosa. T lymphocyte interaction with stromal, bone and hematopoietic cells in the bone marrow.
Immunol Cell Biol 87: 20-29. 2009.
10. A. C. Quinci, S. Vitale, E. Parretta A. Soriani, M. L. Iannitto, M. Cippitelli, C. Fionda, S. Bulfone-Paus, A.
Santoni & F. Di Rosa. IL-15 inhibits IL-7Rα expression by memory-phenotype CD8+ T cells in the bone
marrow. Eur J Immunol 42: 1129-1139. 2012.
D. Research Support (last 5 years)
Ongoing Research Support
CTN01_00177_962865 Grant from Italian Minister of University and Research (01/01/14-31/12/16)
MEDINTECH: Cutting-edge technologies to increase safety and efficacy of drugs and vaccines.
The goal of the project is to optimize the efficacy of vaccines and adjuvants, through the evaluation of their
safety and efficacy.
Role: CNR Lazio Unit PI
Completed Research Support
2009TTTSPM_004 Grant from Italian Minister of University and Research (17/10/11-17/10/13)
Molecular players in angiogenesis and CD8 T cell response: the cytokines VEGF-A and OPN and the
transcription factors HIF-1 alpha and HIF-2 alpha.
The goal of the project is to analyze different transcriptional factors and molecules involved in angiogenesis,
including DC-derived ones, for their effects on polyclonal and antigen-specific CD8 T cell responses
Role: CNR Unit PI
20077EYEXN_002 Grant from Italian Minister of University and Research (22/09/08-22/09/10)
Interaction between Dendritic Cells and CD8 T cells in lymphoid micro-environments for the induction and
maintenance of antigen-specific immune response
The goal of the project was to investigate the CD8 T cell response in PI3kgamma gene-targeted C57BL/6
mice.
Role: CNR Unit PI

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