Integrative biology of immune-mediated inflammatory diseases

Frank_Bertoncelj_Mojca_web.jpg

     Dr. Mojca Frank-Bertoncelj
     Junior Group Leader


Immune-mediated inflammatory diseases (IMIDs) rank among the leading causes of death and disability, and their management represents a significant challenge for today’s healthcare. 
IMIDs develop in an intricate interaction of tissue-resident stromal cells with cells of the immune system. Our research group explores the underlying causes of stromal cell plasticity in IMIDs that influences the tissue composition and behaviour of immune cells. We deconvolute the dynamics of immuno-stromal cell networks in shaping disease variability and therapeutic response and utilize the created knowledge to construct 3D cell-based models of disease for research and drug screens. Our goals are to identify novel drug targets and understand the mechanisms of drug resistance for the accelerated development of targeted therapies and precision medicine in IMIDs. We nurture innovative, collaborative and multidisciplinary research integrating technologies and ideas from molecular biologists, data scientists, engineers and clinicians. 

Web Fig_Final cut2.png

                                                                                                                                                        Created with BioRender.com


Our IMID models include inflammatory arthritis, autoimmune fibrosis and vasculitis, enabling discoveries about the unique and shared immunostromal cell features across organs and inflammatory pathologies. We analyze patient samples and experiment on explanted human tissues, 3D cell-based models and primary human cells applying methodologies of molecular biology, flow cytometry, microscopy, epigenomics, metabolomics, single-cell omics and spatial transcriptomics.

Key areas

  • Tissue resident stromal cells and immuno-stromal cell networks in lung and skin fibrosis, vasculitis, arthritis 
  • Drug target discovery, drug resistance, biomarkers, precision medicine, 3D organ models of human disease

Research projects

  • Arterial wall remodelling at the immuno-stromal cell interface in giant cell arteritis
  • Serum and skin small RNA biomarkers in IgA vasculitis
  • Metabolic perturbations in stromal cells that drive autoimmune fibrosis
  • Understanding synovial immuno-stromal cell interactions for precision medicine in arthritis
  • Joint-specific effects of disease-modifying antirheumatic drugs in arthritis - clinical trials and basic science

Alumni
  • Laura Merlo Pich, Academic guest 2019
  • Ana Županič, MSc, Academic guest 2018 - 2019
  • Joanna Litewka, Intern student 2016
  • Dr. Selene V. Gluck, Intern student 2015
Active memberships in scientific societies and consortia
  • Human Cell Atlas Consortium
  • Walter-Siegenthaler-Gesellschaft für Fortschritte in der Inneren Medizin
  • VTIS Society 
  • EMerging EUropean League of Rheumatism NETwork - EMEUNET
Collaborations

  • University Hospital Zurich: Dr. R. Micheroli, Dr. M. Becker, Prof. Dr. I. Opitz-Schmitz, Prof. Dr. C. Pauli
  • University of Zurich: Prof. Dr. Mark Robinson, Prof. Dr. J. Pelisek
  • University Medical Centre Ljubljana, Slovenia: Prof. Dr. S. Sodin Semrl, Assist. Prof. Dr. K. Lakota, Prof. Dr. M. Tomšič, Assist. Prof. Dr. A. Hočevar, Assoc. Prof. Dr. S. Čučnik, Dr. Ž. Rotar
  • ETH Zurich: Dr. T. Grentzinger, Prof. Dr. O. Voinnet, Prof. Dr. S. Schürle
  • University Hospital Basel, Switzerland: Prof. Dr. D. Kyburz
  • Faculty of Medicine, University of Ljubljana, Slovenia: Assist. Prof. Dr. V. Jurčič, L. Bolha, MSc
  • Stanford University, CA: Prof. Dr. C. Weyand
  • University of Manchester, UK: Prof. Dr. S. Eyre
  • Pfizer: Dr. T. Killeen

Research funding
  • OPO-Stiftung 2020
  • Novartis Foundation for Medical Biological Research 2019
  • Vontobel-Stiftung 2018
  • AbbVie Rheumatology Grant 2017
  • Promedica Stiftung 2015
  • EMDO Stiftung Zurich 2015
  • FOREUM International Fellowship (B. Burja)
Research Awards (selected)
  • 2020 The Scleroderma Workshop Award for Early Career Researchers (B. Burja)
  • 2018 Walter Siegenthaler Medaille in Silber Research Award (M. Frank Bertoncelj)
  • 2015 EULAR Abstract Award for Basic Science (M. Frank Bertoncelj)
Selected publications (2017-2020)

Original papers

  1. Pachera E, Assassi S, Salazar GA, Stellato M, Renoux F, Wunderlin A, Blyszczuk P, Lafyatis R, Kurreeman F, de Vries-Bouwstra J, Messemaker T, Feghali-Bostwick CA, Rogler G, van Haaften WT, Dijkstra G, Oakley F, Calcagni M, Schniering J, Maurer B, Distler JH, Kania G, Frank-Bertoncelj M, Distler O. Long noncoding RNA H19X is a key mediator of TGFβ driven fibrosis. J Clin Invest. 2020; 135439.
  2. Bolha L, Pižem J, Frank-Bertoncelj M, Hočevar A, Tomšič M, Jurčić V. Identification of microRNAs and their target gene networks implicated in arterial wall remodelling in giant cell arteritis. Rheumatology (Oxford). 2020; keaa204.
  3. Burja B, Kuret T, Janko T, Topalović D, Živković L, Mrak-Poljšak K, Spremo- Potparević B, Žigon P, Distler O, Čučnik S, Sodin-Semrl S, Lakota K, Frank-Bertoncelj M. Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells. Front. Cardiovasc. Med. 2020; 6: 56.
  4. Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H., Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C. Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions. Nat. Commun. 2017; 8: 14852.

Review papers

  1. Burja B, Mertelj T, Frank-Bertoncelj M. (2020) Hi-JAKi-ng Synovial Fibroblasts in Inflammatory Arthritis With JAK Inhibitors. Front. Med. 2020; 7: 124.
  2.  Ospelt C, Frank-Bertoncelj M. Why location matters - site-specific factors in rheumatic diseases. Nat. Rev. Rheumatol. 2017; 13(7): 433-42.

Conference abstracts

  1. Edalat S.G., Micheroli R, Kuret T, Bürki K, Pauli C, Sodin Semrl S, Ciurea A, Distler O, Ospelt C, Rot G, Frank Bertoncelj M. Integrated analysis of synovial single cell RNA sequencing data deepens the current knowledge of synovial pathology in arthritis. Ann Rheum Dis 2020; 79 (Suppl. 1): 215.
  2. Burja B, Kania G, Tomsic M, Sodin-Šemrl S, Distler O, Lakota K, Frank- Bertoncelj M. Integrative transcriptomic and functional analysis reveals a role of dimethyl-α-ketoglutarate in TGFβ-driven cytoskeleton regulation and myofibroblast differentiation. Ann Rheum Dis 2020; 79 (Suppl. 1): 1086.
  3. Županič A, Burja B, Klein K, Micheroli R, Distler O, Ospelt C, Frank-Bertoncelj M. Proinflammatory responses in the JAK-STAT pathway in synovial fibroblasts are stimulus-specific and only partially inhibited by therapeutic doses of tofacitinib. Ann Rheum Dis 2019; 78 (Suppl 2): 270-1.
  4. Hocevar A, Lakota K, Grentzinger T, Sarazin A, Brezovec N, Kuret T, Distler O, Cucnik S, Voinnet O, Sodin-Šemrl S, Tomšič M, Frank-Bertoncelj M. RNA sequencing identifies an IgA vasculitis associated serum microRNA signature, discriminating patients with IgA vasculitis from age- and sex-matched healthy subjects. Ann Rheum Dis 2019; 78(Suppl 2): 1192-3.
  5. Ciurea A, Distler O, Tim K, Ermeg A, Kwok K, Wang L, Ospelt C, Frank-Bertoncelj M. Joint-specific responses to tofacitinib and adalimumab in rheumatoid arthritis: a post hoc analysis of data from ORAL Standard and ORAL Strategy. Ann Rheum Dis 2019; 78 (Suppl 2): 742-3.





We use cookies to make our website user-friendly, to continuously improve it and to analyze the traffic of our website. By continuing to browse the site, you are agreeing to our use of cookies. Further information can be found in our privacy policy.