Epithelial Stem Cell Biology & Regenerative Medicine

Our research focuses on the biology of epithelial stem cells and its future clinical translation, especially in the context of tissue engineering for organ reconstruction. Epithelia line the outer and inner surfaces of our body and play crucial role in tissue homeostasis and repair. Epithelia have a complex biology, understood only in part, and despite some common features, they diversify to fulfil their specific role and function.

We aim at understanding the underlying molecular and cellular mechanisms that regulate epithelia self-renewal and differentiation, with the final goal to produce long lasting, tissue engineered, medicinal products.

We primarily focus on the thymus, whose epithelial cells contribute to the microenvironment that instructs lymphoid precursors to establish proper immunity against pathogens and also to induce self-tolerance that prevents autoimmunity. We aim to dissect the components of thymus microenvironment and study their role in regulating tolerance and immune cell maturation.

Our lab is studying human epithelial oesophageal stem/progenitor cells to reconstruct a functional and growing epithelium necessary to guarantee long term repair of the epithelial barrier of the gastro-intestinal tract. We use in vitro culture systems and tissue engineering approaches to provide a functional, long-lasting epithelium for the therapy of neonatal oesophageal atresia, and other congenital and acquired disorders.

We are building also in vitro model systems to dissect fate and potency of human pancreatic progenitors. We aim at identifying intrinsic factors and environmental cues that dictate fate choices of these progenitors during pancreas development to define conditions that will allow differentiation of stem cells to insulin-producing beta-cells for possible cell therapy of diabetes.

Finally, we are exploring the use of gene-editing technology by CRISPR/Cas9 for correction of Cystic Fibrosis Trans-membrane conductance Regulator (CFTR) in airways epithelial cells in vitro.

Array of six figures

Figures: 1. Rhodamine-B staining of thymic epithelial colonies as they appear in culture; 2. Immunofluorescence of cultivated thymic epithelial cells (Pan-cytokeratin, green; Ki67, red; nuclei, blue); 3. Immunofluorescence of pancreatic progenitors grown in a 3D matrix (E-Cadherin, green; Sox9, red); 4. Immunohistochemistry of a developing oesophagus (P63, green; Ki67, red; nuclei, blue); 5. Immunocytochemistry of oesophageal epithelial cells as they appear in culture (Cytokeratin 13, green; Cytokeratin 14, red; nuclei, blue); 6. Normal Human Bronchial Epithelial Cells on ALI culture (Zo-1, red; ac-tubulin, green; nuclei, blue).

Selected Publications

Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stangé G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CVE, Van de Casteele M, German MS, Bouwens L & Heimberg H. Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice. Nature Biotechnology. 2014 Jan;32(1):76-83

Huch M*, Bonfanti P*, Boj SF*, Sato T*, Loomans CJM, van de Wetering M, Sojoodi M, Li VS, Schuijer J, Gracanin A, Ringnalda F, Begtel H, Hamer K, Mulder J, van Es JH, de Koning E, Vries RG, Heimberg H and Clevers H. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/Rspondin axis. EMBO J. 2013 Oct 16;32(20):2708-21

Bonfanti P, Claudinot S, Amici AW, Farley A, Blackburn CC and Barrandon Y. Microenvironmental Reprogramming of Thymic Epithelial Cells to Skin Multipotent Stem Cells. Nature. 2010 Aug 19;466(7309):978-82 

Paola Bonfanti

Paola Bonfanti

paola.bonfanti@crick.ac.uk
+44 (0) 20379 63531

  • 2001 MD, University of Milan| Italy
  • 2002 Membership Board of Physicians and Surgeons |Italy
  • 2003 Research visitor, The Sanford-Burnham Institute, La Jolla, San Diego | USA
  • 2008 PhD, École Polytechnique Fédérale de Lausanne, EPFL | Switzerland
  • 2011 EMBO Postdoctoral Fellow, Diabetes Research Center, Vrije Universiteit Brussel, VUB | Belgium
  • 2014 Junior Group Leader, UCL-Rosetrees Excellence Fellow, Great Ormond Street Institute of Child Health, University College London, UCL | UK
  • 2017 Group Leader, the Francis Crick Institute, London | UK