Benedetta Bussolati
CURRICULUM VITAE
Born in Torino; 25th November 1969
-1988: Graduation at the classical lyceum "V. Alfieri" in Torino;
-1994: Medical degree at the Medical School, University of Torino, obtaining the valuation of
110/110 cum laude,
-November 1995-october 1998: PhD in "Physiopathology of the Renal Insufficiency" at the
University of Parma
-1998-July 1999: Research Visiting Fellow at the Laboratory of Vascular and Reproductive
Physiopathology, directed by Prof. Asif. Ahmed, University of Birmingham, UK
- July1999-2001: post-Doc position at the Laboratory of Renal Immunopathology, University of
Torino under the direction of Prof. Giovanni Camussi;
-October 2001: position of Assistant Professor in Pharmacology, University of Torino, Department
of Biological and Clinical Sciences
-2006: assistant Professor of Nephrology, University of Torino, Department of Internal Medicine
Dr. Bussolati is author of >115 original articles on peer-reviewed journals.
http://www.ncbi.nlm.nih.gov/pubmed/?term=Bussolati+B
H-factor: 28
EDITORIAL ACTIVITY
Guest Editor of Organogenesis, Issue 7, 2011 on Cell Therapies for Organ Repair
Editorial board of ISRN Stem Cells
Editorial Board of Nephrology Dialysis and Transplantation
Co-Editor of J. Nephrology
Grants
2000-2001. Grant for Joung Researchers
2002-2003. Grant of the Regione Piemonte. Identificazion of markers of the neoformed
endothelium
2005-2007. Cofin (Ministry of research): “Isolation and identification of CD133+ renal stem cells”.
2006-2008 Grant of the Regione Piemonte. Role of hemopexin in renal damage.
2008-2010. Piedmont Region: Molecular alterations in renal cancer stem cells.
2011-2014 European Research Training Network: Nephrotools.
Patents:
1-“Peptidic sequences binding human tumor endothelial cells and their use" TO2005A000233.
2- “Liver progenitor cells” International Patent Application N. PCT/IT2005/000303.
3. Isolated Multipotent Mesenchymal Stem Cell From Human Adult Glomeruli (Hgl-Msc), A
Method Of Preparing Thereof And Uses Thereof In The Regenerative Medicine Of The Kidney
(pat. App. N. 20110256111, 10/20/2011)
TRAINING
Dr Bussolati is involved in training of graduate students and is currently Tutor of 4 PhD students.
SCIENTIFIC ACTIVITY
She focused in renal immunopathology, working on the role of cellular mediators, of bacterial and
viral products and of acute phase proteins in glomerular inflammation, progression of the tubulointerstitial damage and in septic shock. She acquired experience in angiogenesis, working in
particular on the reciprocal role of VEGF receptor 1 and 2 and on the molecular characteristics of
tumor angiogenesis in renal carcinomas. More recently, she focused her research on stem cells.
Stem cells
She was the first to identify in the human adult kidney a population of resident progenitor cells
CD133+, able to growth in vitro in non-differentiated state and able to differentiate in vitro and in
vivo into endothelial and epithelial cells (Am J Pathol. 2005). Moreover, she showed that CD133+
renal cells are present in renal carcinomas and contribute to tumor vascularization and growth (Am
J Pathol 2006). She also showed that murine mesenchymal stem cells home to injured kidney and
contribute to the repair of the local damage in the same model of acute renal failure. (Int J Mol Med
2004). She also showed that murine mesenchymal stem cells home to injured kidney and contribute
to the repair of the local damage in a model of acute renal failure and she that CD44 mediates their
homing (Kidney Int 2007). In addition she contributed to the first identification of a population of
multipotent progenitor cells in the liver (Stem Cells 2006)and she identified the possibility to use
microvescicles derived from endothelial progenitor cells (EPC) to induce angiogenesis (Blood
2007). Moreover, she recently identified a population of renal tumor stem cells in renal carcinomas,
with tumor-initiating and vasculogenic properties (FASEB J 2008).
Angiogenesis
She studied in vitro and in vivo the role of soluble factors and of cellular receptors in inflammatory
and tumor angiogenesis and she investigated the characteristics of the angiogenesis present in the
renal carcinoma In particular:
1) She showed a new angiogenic role for PAF in breast cancer (Am J Pathol. 153:1589, 1998).
2) She studied the mechanisms of the development of Kaposi’s sarcoma showing the role of PAF
(Am J Pathol 155:1731, 1999) and of oxytocin (Cancer Res. 62:2406, 2002). She also showed that
activation of the Pax-2 embryonic gene, a transcription factor involved in renal development, favors
the transformation of normal endothelial cells (J Biol Chem 279:4136).
3) She described a new role for the VEGF receptor-1 as a negative modulator of angiogenesis (Am.
J. Pathol. 159: 993, 2001). She also showed that VEGF-induced activation of heme-oxygenase
possess a dual role in inflammatory angiogenesis, (Blood. 103:761, 2004), inhibiting the
inflammatory angiogenesis while favoring the endothelial angiogenesis necessary for the tissue
repair.
4) She studied the mediators involved in placental development and in the pathogenesis of preeclampsia (Mol Med.6:391, 2000). She also showed the involvement of angiopoietin-1 in placental
vascular development (Am J Pathol. 156:2185, 2000).
5) She showed the role of PAF in angiogenesis induced by activation of CD40 receptor on
endothelial cells (J Immunol. 171:5489, 2003), and the transduction pathways involved (J Biol
Chem. 278:18008, 2003). She also showed that CD154, the CD40 receptor, stimulates the
production of angiogenic factors by renal carcinoma cells and that its expression correlates with the
tumor stage (Int J Cancer. 100:1035, 2002).
6) She studied the molecular and functional properties of endothelial cells derived from the renal
carcinoma, showing that these cells are different from normal endothelial cells in terms of survival,
apoptosis resistance and in vitro and in vivo angiogenesis (FASEB J, 17:1159, 2003).In particular,
she investigated the characteristics of the angiogenesis present in the renal carcinoma and
characterized tumor-derived endothelial cells at functional and molecular level, showing their
embryonic/immature characteristics (J Mol Med 2006, Exp Cell Res 2006)and the involvement of
Pax2 as an onco-angio gene (Am J pathol 2005). She identified using phage display technology
peptides able to selectively bind and target endothelial cells derived from renal carcinomas in vivo.
Moreover, she showed the possibility to exploit the expression of NCAM, an adhesion molecule, on
tumor endothelial cells for molecular imaging in vivo using magnetic resonance(Cancer Res 2007, J
Mol Med 2007). She identified the vasculogenic potential of breast and renal tumor stem cells (J
Cell Mol Med 2008 and FASEB J 2008).
Renal Immunopathology
Dr. Bussolati studied the role of cellular mediators, of bacterial and viral products and of acute
phase proteins in the glomerular inflammation and in the progression of the tubulo-interstitial
damage. In particular:
1) She showed the presence of the IL-12 Receptor beta-1 on glomerular mesangial cells and the
ability of these cells to produce IL-12. She also showed the effect of IL-12 on mesangial cell
contraction and on the production of platelet-activating factor (PAF) and oxygen radicals,
suggesting a role for the inflammatory Th1 lymphocyte reactions in glomerular inflammation (Am J
Pathol. 29:1513, 1999). Moreover, she showed an intracellular balance among PAF and nitric oxide
in mesangial cells, involved in mesangial cell-leukocyte adhesion (Kidney Int. 62:1322, 2002).
2) She studied the pathogenesis of the tubulo-interstitial damage during glomerular nephropathies, a
negative prognostic factor that correlates with the entity of proteinuria. She studied the role of the
proximal tubular epithelial cells in the initiation of the tubular renal damage due to complement
activation (Nephrol. Dial. Trasplant. 11: 12:51, 1997).
3) She studied the role of the LPS receptor CD14 on renal mesangial and tubular cells (J Immunol
155:316, 1995). She also showed that proximal tubular epithelial cells are stimulated by the
complex solubleCD14-LPS to produce pro-inflammatory cytokines. She isolated the solubleCD14LPS complex from proteinuric urine showing the activation of tubular epithelial cells. This study
suggests a mechanism of progression of the tubulo-interstitial damage due to renal infections in
patients with proteinuria (Int. J. Mol. Med. 10:441, 2002).
4) She demonstrated that IL-10 induces PAF synthesis from lupus patients and that PAF production
correlates with the disease state (Clin. Exp. Immunol. 122:471, 2000).
5) She showed the presence of an acute phase protein, pentraxin-3 (PTX-3) in inflammatory
glomerulonephritides, in particular in IgA nephropathy (J. Immunol. 170:1466, 2003).
6) She demonstrated the role of the HIV-1 protein Tat in glomerular podocyte proliferation and in
the podocyte production of pro-inflammatory and fibrogenic cytokines (Am J Pathol. 161:53,
2002), suggesting a role for Tat in the pathogenesis of glomerular damage observed in HIV-1
nephropathy.
Inflammation
She studied the role of cellular mediators in the pathogenesis of the septic shock and she showed the
role of PAF in the amplification of the non specific immune reaction (monocytes, granulocytes and
NK cells). In particular:
1) She showed that IL-12, a Th1 cytokine involved in NK cytotoxicity, induces PAF synthesis
whereas IL-10, a Th2 anti-inflammatory cytokine, inhibits this production in inflammatory cells
(Immunol. 90:440, 1997; J. Immunol. 161:1493, 1998)
2) She showed the role of PAF in the monocyte motility induced by HIV-1 Tat protein (Eur. J.
Immunol. 29:1531, 1999).
3) She showed that stimulation of the CD14 receptor for LPS induces PAF synthesis in
inflammatory cells (J Immunol 155:316, 1995). Moreover, she studied the role of nitric oxide in
modulating PAF synthesis from monocytes, endothelial and polymorphonuclear cells (Shock
19:339, 2003).
At the present, her main research interests are: 1-the properties and the mechanisms of plasticity of
progenitor cells in normal tissue, diseased tissue and carcinomas. 2- the paracrine effect of stem
cells and the role of stem cell released factors on tissue regeneration 3- the fate using MRI or
fluorescence imaging of in vivo injected stem cells or bio-products.