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SBSC Dipartimento di Scienze Biomediche Sperimentali e Cliniche

Gruppo Romagnani

Coordinator of Research Team

Name                                                                                 Paola Romagnani

Position                                                                                    Full Professor

Name of Research Team/Laboratory                      Laboratory of Nephrology

e-mail                                                                     paola.romagnani@unifi.it

telephone number                                                                     055 2758167

 

 


Renal progenitor cells (RPC) can be visualized and tracked in vivo by using two transgenic mouse models recently developed in Romagnani’s lab. Left: In the Pax2.rtTA;TetO.Cre;R26.Confetti mouse, RPC express four different fluorochromes and appear as cells localized in the parietal epithelium of the Bowman capsule in the glomeruli (G) and as scattered cells along different tubular segments. Right: By using the Pax2.rtTA;TetO.Cre;R26.Tm/GFP mouse as a RPC-specific tracking tool, we could establish that RPC differentiation into podocytes can occur following glomerular injury and critically contributes to disease improvement. Reproduced from Lasagni et al. (2015) Stem Cell Reports 5, 248-263.

 

Brief biographical sketch of the Coordinator

Paola Romagnani was born on March 7th 1970. She received her Master Degree in in Medicine and Surgery, Faculty of Medicine and Surgery, University of Florence, Italy, the PhD in Endocrinology and Metabolism, University of Florence/Italy, the Specialization in Nephrology, Dialysis and Transplantation, University of Florence, Italy. She was Associate Professor of Nephrology from 2006 to 2014 and is now Full Professor at the University of Florence. She is Head of Nephrology and Dialysis Clinical Unit at the Meyer Children’s Hospital of Florence, Italy.

 

Member of the scientific board of the Doctorate/PhD Program in………………………………………………..

International School for PhD Students in Pharmacology and Innovative Treatments/ University of Florence, Italy

 

Member of the following Scientific Societies

1)      Associated Member, International Society of Nephrology

2)      Associated Member, European Renal Association/European Dialysis and Transplant Association (ERA-EDTA)

3)      Associated Member, American Society of Nephrology

4)      Associated Member, Italian Society of Nephrology

 

Member of the editorial board of the following Journals

1)      Scientific Advisory Board, ERA-EDTA (European Renal Association/European Dialysis and Transplant Association)

2)      Associate Editor/Plose One

3)      Editorial Board/Journal of the American Society of Nephrology

4)      Co-Editor in Chief/Journal of Nephrology

5)      Associate Editor/Fibrogenesis and Tissue Repair

 

Research Team

                1) Paola Romagnani, Full Professor, 07/03/1970, paola.romagnani@unifi.it

                2) Laura Lasagni, Associate Professor, 24/11/1964, laura.lasagni@unifi.it

                3) Elena Lazzeri, Associate Professor, 06/12/1974, elena.lazzeri@unifi.it

                4) Anna Julie Peired, post.doc, 12/09/1977, anpeired@unifi.it

5) Maria Lucia Angelotti, post-doc, 04/06/1982, marialucia.angelotti@unifi.it

6) Carolina Conte, fellow, 30/03/1990, carolinaconte3@gmail.com

7) Sara Nardi, PhD fellow, 05/05/1986, sara.nardi05@gmail.com

8) Giulia Antonelli, fellow, 12/11/1990, giulia.antonelli@libero.it

9) Maria Elena Melica, fellow, 06/02/1989, mariaelena.melica@gmail.com

9) Marco Allinovi, MD, 03/10/1983, marco.allinovi@gmail.com

10) Francesca Becherucci, MD, 27/06/1982, francesca.becherucci@gmail.com

11) Letizia De Chiara, post doc, 24/02/1985, letizia.dechiara@gmail.com

12) Fiammetta Ravaglia, MD, 18/10/1986, ravaglia.fiammetta@gmail.com

13 Giulia Sansavini, MD, 07/09/1985, g.sansavini@gmail.com

 

Current research interests 

Kidney disorders represent a major global health issue and new tools are needed to expand disease modeling and therapeutic options. The identification of renal progenitors (RPC) opens a wide range of possibilities to support progress in several fields of nephrology. Indeed, RPC have become a key player in the pathogenesis of kidney disorders, and their study is increasing knowledge about the mechanisms of kidney response to injury. In the last years, we developed new lineage tracing models to identify and characterize mouse RPC system. Using lineage tracing of the murine RPC system from development to adult life, we aim to characterize the RPC niche through observation of RPC at various stages of nephron formation during development as well as during kidney growth, homeostasis and aging. Moreover, we are using these models to establish RPC role in progression or resolution of glomerular and tubular injury, and the mechanisms involved in these processes. This knowledge is the starting point to validate RPC as therapeutic targets to improve podocyte regeneration and disease regression. Indeed, the identification of new drugs that can promote kidney regeneration by enhancing activity of RPC is one of the most promising SC-based therapeutic option for kidney disorders. We thus use in vitro cultures of human RPCs as a platform for first-step screening of a library of synthetic chemicals for their potential effects on the regeneration of podocytes and tubular cells. Using this approach, we are selecting some compounds and validating them in a transgenic mouse model of human focal segmental glomerulosclerosis and/or acute kidney injury where RPC can be traced to evaluate their response to different treatments.

Moreover, using our unique transgenic mouse models that allow tracking RPC, we are analyzing the role of abnormal RPC function in the pathogenesis of renal cell carcinoma. Indeed, identification of the cell of origin of kidney cancers may permit a more systematic analysis of the genetic lesions involved in tumor initiation and progression and might form the basis of novel cancer therapies.

Finally, the recent development of a method for culturing RPC specifically from urine of patients affected by renal diseases finally opens the perspective of personalized medicine of the kidney and the development of patient-specific treatments. This new strategy allows us also to complement the extended genetic diagnosis of kidney disease performed in our Unit thanks to the close collaboration of the Genetic Unit of Meyer Children’s Hospital, providing a unique clinical approach for to patients affected by kidney diseases.

This method may be applicable for any patient with inherited kidney disorders of the kidney, and used for functional studies of individual mutations. In this perspective, this technique ideally complements state-of-the-art genetic diagnostics through next-generation sequencing strategies and allows study of the role of epigenetics to clinical expression of the disorder. In addition, patient-specific RPC can be used for screening of new treatment strategies in terms of safety and efficacy.

 

Current / recent sources of funding

1)      PROGETTO "Smart" BANDO FAS SALUTE, Sviluppo Toscana. Messa a punto di una strategia innovativa di medicina personalizzata per la diagnosi e la trerapia delle malattie renali nei bambini.

2)      RENOIR, ERC Consolidator Grant, 2014, Horizon 2020, RENal prOgenItoRs as tools to understand kidney pathophysiology and treat renal disorders

3)      STELLAR, FP7-HEALTH-2012, Stem-cell based therapy for kidney repair.

4)      VITA- Bando NUTRACEUTICA, Regione Toscana, Uso della supplementazione dietetica con vitamina A per promuovere la regressione delle malattie renali croniche.

5)      Kidney Connect: A Gateway to European Kidney Research Resources, FP7-Cost Project

6)      Kidney Research UK: Miracle in collecting ducts underlie albuminuria-induced kidney fibrosis.

7)      Star-trek, FP7, HEALTH-F5, Set up and comparison of multiple stem cell approaches for kidney repair.

8)      Italian Ministery of Health “Set up of Stem cell strategies for acute and chronic renal failure”

9)      Regione Toscana “Renal stem cells amplification from the urine of patients with glomerular disorders for the set-up of autologous cell therapy of chronic renal injury”

10)  RESCARF, ERC-Starting Grant, FP7. Renal stem cells: possible role in kidney pathologies and as new therapeutic tools.

 

10 publications of the last 5 years

1) Lasagni L, Angelotti ML, Ronconi E, Lombardi D, Nardi S, Peired A, Becherucci F, Mazzinghi B, Sisti A, Romoli S, Burger A, Schaefer B, Buccoliero A, Lazzeri E, Romagnani P. Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease Remission and Can Be Pharmacologically Enhanced. Stem Cell Reports. 2015 Aug 11;5(2):248-63.

2) Romagnani P, Rinkevich Y, Dekel B. The use of lineage tracing to study kidney injury and regeneration.

Nat Rev Nephrol. 2015 Jul;11(7):420-31.

3) Giglio S, Provenzano A, Mazzinghi B, Becherucci F, Giunti L, Sansavini G, Ravaglia F, Roperto RM, Farsetti S, Benetti E, Rotondi M, Murer L, Lazzeri E, Lasagni L, Materassi M, Romagnani P. Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression. J Am Soc Nephrol. 2015 Jan;26(1):230-6.

4) Lazzeri E, Ronconi E, Angelotti ML, Peired A, Mazzinghi B, Becherucci F, Conti S, Sansavini G, Sisti A, Ravaglia F, Lombardi D, Provenzano A, Manonelles A, Cruzado JM, Giglio S, Roperto RM, Materassi M, Lasagni L, Romagnani P. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders. J Am Soc Nephrol. 2015 Aug;26(8):1961-74.

5) Peired A, Angelotti ML, Ronconi E, la Marca G, Mazzinghi B, Sisti A, Lombardi D, Giocaliere E, Della Bona M, Villanelli F, Parente E, Ballerini L, Sagrinati C, Wanner N, Huber TB, Liapis H, Lazzeri E, Lasagni L, Romagnani P. Proteinuria impairs podocyte regeneration by sequestering retinoic acid. J Am Soc Nephrol. 2013 Nov;24(11):1756-68.

6) Romagnani P, Lasagni L, Remuzzi G. Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol. 2013 Mar;9(3):137-46.

7) Lasagni L, Ballerini L, Angelotti ML, Parente E, Sagrinati C, Mazzinghi B, Peired A, Ronconi E, Becherucci F, Bani D, Gacci M, Carini M, Lazzeri E, Romagnani P. Notch activation differentially regulates renal progenitors proliferation and differentiation toward the podocyte lineage in glomerular disorders. Stem Cells. 2010 Sep;28(9):1674-85.

8) Ronconi E, Sagrinati C, Angelotti ML, Lazzeri E, Mazzinghi B, Ballerini L, Parente E, Becherucci F, Gacci M, Carini M, Maggi E, Serio M, Vannelli GB, Lasagni L, Romagnani S, Romagnani P. Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol. 2009 Feb;20(2):322-32.

9) Mazzinghi B, Ronconi E, Lazzeri E, Sagrinati C, Ballerini L, Angelotti ML, Parente E, Mancina R, Netti GS, Becherucci F, Gacci M, Carini M, Gesualdo L, Rotondi M, Maggi E, Lasagni L, Serio M, Romagnani S, Romagnani P. Essential but differential role for CXCR4 and CXCR7 in the therapeutic homing of human renal progenitor cells. J Exp Med. 2008 Feb 18;205(2):479-90.

10) Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, Ronconi E, Meini C, Gacci M, Squecco R, Carini M, Gesualdo L, Francini F, Maggi E, Annunziato F, Lasagni L, Serio M, Romagnani S, Romagnani P. Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys. J Am Soc Nephrol. 2006 Sep;17(9):2443-56.

10)

 

Previous research experiences

In her career, she was responsible for other important scientific breakthroughs. In 2001, she clarified the mechanisms involved in the angiostatic effects of chemokines. This study (Romagnani P et al. JCI, 2001), was selected for the cover of the journal and was the subject of a highlight of the Editor. She has then identified and functionally characterized a novel chemokine receptor involved in cell growth control (Lasagni L et al. J Exp Med, 2003). In 2005, she has demonstrated the existence of a previously unrecognized population of circulating stem cells (Romagnani P et al. Circ Res, 2005).

 

 

Main scientific contributions

-Characterization of the renal progenitor system in adult human kidney and demonstration of its capacity to generate novel podocytes as well as tubular cells of different portions of the nephron.

-Generation of an unique mouse model for lineage tracing of the renal progenitor system in the mouse.

-Elucidation of the mechanisms of podocyte regeneration driven by renal progenitors.

-Elucidation of the cellular mechanisms activated in the kidney following acute kidney injury.

-Establishment of a method for selection and identification of renal progenitors from the urine of patients affected by kidney disorders.

-Clarification of the mechanisms involved in the angiostatic effects of chemokines

-Identification and functional characterization of a novel chemokine receptor (CXCR3B) involved in cell growth control

-Demonstration of the existence of a previously unrecognized population of circulating stem cells

 

Collaborations

  • Hans-Joachim Anders/Basic and Clinical Nephrology/ Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München-Innenstadt, Munich, Germany.
  • Giuseppe Remuzzi/Basic and Clinical Nephrology. Mario Negri Institute for Pharmacological Research, Bergamo, Italy
  • Qihe Xu/Basic researcher, Metabolism/King’s College, London, UK
  • Ton Rabelink/Clinical Researcher, Internal Medicine/LMU Leiden University Medical Center/Ledien, The Netherlands
  • Benjamin Dekel/Basic and Clinical Pediatrics and Nephrology/Tel Aviv University, Tel Aviv, Israel
  • Tobias Huber/Basic Nephrology/University Medical Center Freiburg/Freiburg, Germany
  • Janos Peti-Peterdi/Basic research, Physiology, University of South California, Los Angeles, USA

 

 

Other relevant information

From 2011, Paola Romagnani is included in AcademiaNet (www.academia-net.org), the database of outstanding female scientists organized by Robert Bosch Stiftung’s foundation in collaboration with Nature.

She is Director of the Specialty School in Nephrology/University of Florence/Italy and member of the Scientific Committee of the Excellence Center DEONTHE/University of Florence/Italy

Links

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ultimo aggiornamento: 12-Set-2017
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