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Professor Daniela Riccardi

Professor Daniela Riccardi

Deputy Head of School

School of Biosciences

Email
riccardi@cardiff.ac.uk
Telephone
+44 (0)29 2087 9132
Fax:
+44 (0)29 2087 4116
Campuses
C3.15, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Users
Available for postgraduate supervision

Overview

The ability of cells to monitor changes in the environment is crucial to life. In humans, excessive exposure to certain noxious external cues can result in a variety of life-threatening diseases such as asthma, smoker’s cough (COPD) and scarring of the lung (pulmonary fibrosis). Previously in my laboratory we have discovered the existence of “sensors” throughout our body. Currently we are investigating: i) The ability of noxious stimuli such as smoke and urban particulate matter to activate these sensors; ii) The consequences of aberrant activation of these sensors at the molecular, cellular and whole organism level; iii) The possibility to use new and existing drugs targeting these sensors to specifically prevent currently incurable inflammatory lung disease.

Roles

Executive Team: Deputy Head of School 
Major Committee Chair: Staff and Work Environment Committee

Useful links

Development of inhaled CaSR antagonists, calcilytics, for asthma:

https://www.youtube.com/watch?v=jIqz46r9thU&feature=youtu.be

Calcilytics as novel therapeutics for pulmonary fibrosis:

https://www.medrxiv.org/content/10.1101/2020.03.12.20034751v1

Biography

I obtained my BA in Zoology and MRes in Physiopathological methods from the University of Milan, Italy, where I investigated mechanisms of fluid transport across mammalian epithelia. I did my PhD in Physiology working between the University of Milan and the Harvard Medical School, Boston, MA, USA, under the supervision of Prof. SC Hebert, in the Renal Division of the Brigham and Women's Hospital. There, in 1993 we identified the first G protein-coupled receptor for an ion, calcium. The paper describing the cloning of the Calcium-Sensing Receptor, CaSR, from parathyroid glands is now a "citation classic" with >2,000 citations. While in Prof Hebert lab, I was awarded a Research Fellowship from the National Kidney Foundation to identify the renal CaSR. The parathyroid and kidney CaR are the target for a novel class of small molecule drugs, the calcimimetics, which were developed for the treatment of chronic kidney disease. In 2004, calcimimetics were the first G protein-coupled receptor allosteric modulators to enter the market and in 2014 calcimimetics were within the top 100 most sold drugs. In 1997, I moved to the UK where I established my independent research group at Manchester University and in 2004 I moved to Cardiff University as a Reader, then Professor (2012) within the School of Biosciences. Currently my group is actively pursuing the development of CaSR-based therapeutics for the treatment of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis.

Honours and awards

  • 2002 - John Haddad Young Investigator Award (AIMM/ASBMR)
  • 2000 - The Wellcome Trust Prize for Excellence in Physiology
  • 1995 - First Prize,  Excellence in Research (ASN/NKF)

Professional memberships

  • 2018 - European Respiratory Society
  • 2018 - Welsh Thoracic Society
  • 1997 - Physiological Society

Academic positions

  • 2015 - present: Deputy Head of School
  • 2004 - present: Reader and Professor, Cardiff University
  • 1997 - 2004: Lecturer and Senior Lecturer, University of Manchester, UK
  • 1993 - 1997: Research Fellow, renal Division, Harvard Medical School, Boston, MA USA

Speaking engagements

Asthma UK Day: the opportunity of asthma research in Wales (2017)

Committees and reviewing

  • Journal reviewer (e.g., Nature, PNAS, JCI, Science TM, Scientific Reports...)
  • Physiological Society Council (2012-2016)
  • BBSRC pool of experts (2015-2017)

Publications

2021

2020

2019

2018

2017

2016

2015

2014

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2003

2002

2001

2000

Teaching

Module contributor: BI2331 Physiology
Module contributor: BI3355 Advances in Physiology and Pathophysiology

Research goal: to develop CaSR antagonists, calcilytics, as novel therapeutics for pulmonary diseases such as asthma, COPD and pulmonary fibrosis

Asthma remains incurable, a major and increasing cause of global suffering and premature death and affects 340 million people worldwide. Current standard asthma therapy is palliative and 5-10% of asthma sufferers do not respond to any treatment at all. What is needed is a new approach to asthma therapy which is safe, that targets the underlying cause of the disease and that prevents environmentally-induced asthma exacerbations. During asthma, the expression of certain polycations such as eosinophil cationic protein, major basic protein, spermine and spermidine) and of polyamines such as poly-L-arginine is increased. We have made the discovery that the CaSR is expressed in the airways, where activation of this receptor by polycations and polyamines drives airways hyperreactivity, bronchoconstriction and inflammation in allergic asthma (Figure 1). Excitingly, blocking the CaSR using calcilytics, we could prevent all of these effects (Yarova et al, 2015). Recently we have also shown that inhaled calcilytics suppress inflammation as well as the current standard-of-care, inhaled corticosteroids, but they also suppress airway hyperresponsiveness and remodelling while corticosteroids do not (Yarova et al, JPET 2020)(Figure 2).

Recently my laboratory has also made the discovery that the CaSR can also be activated by chemicals contained in cigarette smoke and car fumes, and by urban particulate matter (Mansfield et al, 2019)(Figure 3), strongly implicating the CaSR in the development of currently untreatable diseases such as COPD (smoker’s cough) and idiopathic pulmonary fibrosis (Wolffs et al, 2020).

Oral calcilytics were initially developed as an anti-osteoporosis drug. While they were safe and well-tolerated in patients, their development was terminated due to lack of efficacy for this indication. Our goal is repurpose existing calcilytics, delivered topically to the lung, as novel therapeutics to treat inflammatory lung disorders in people.  In addition, in collaboration with Prof Andrea Brancale (Cardiff School of Pharmacy), we are also developing entirely novel calcilytics with an optimal lung delivery profile for the treatment of lung disease.

Patent: WO2014049351 Calcium/cation-sensing receptor (casr) antagonist like nps89636 for use in treating inflammatory lung disorders (asthma or copd)

References:

Collaborators

National
  • Profs A Brancale, K Broadley, B Hope-Gill, G Taylor, Drs EJ Kidd, WR Ford, B Kariuki, (Cardiff);
  • Prof K Lewis (Swansea University and Respiratory Innovation Wales);
  • Prof L Mur (Aberystwyth University);
  • Profs CJ Corrigan, JPT Ward, C Page and C Hawrylowicz (King's College London)
  • Prof D Thickett (Birmingham University)
  • Dr DT Ward (Manchester University)
International
  • Prof E Kallay, Dr M Schepelmann (Vienna University)
  • Dr I Ellinger, R Ecker (TissueGnostics, Vienna)
  • Dr W Chang (UCSF, USA)
  • Prof G Gamba, Mexico City (UNAM)
  • Prof YS Prakash and C Pabelick (Mayo Clinic, Rochester, USA)
  • Dr M Ranieri, Prof G Valenti (University of Bari, Italy)
  • Prof S Ying (CMU, China)
Work funded by

Asthma UK, King's Commercialisation Institute, The Live Sciences Research Network, Marie Curie ITN “Multifaceted CaSR” and Marie Curie ETN “CaSR Biomedicine", KESS2 studentship, the Saunders Legacy Research Fund

Active research grants
  • Marie Curie ETN "Biomedicine"
  • KESS2 studentship

Supervision

  • Role of the calcium-sensing recepto in inflammatory lung disease
  • Novel therapies for asthma, chronic obstructve pulmonary disease and pulmonary fibrosis
  • Mechanisms of pathological vascular calcification
  • Calcium-sensing receptor-based therapeutics for pulmonary disease

Past projects

All my PhD students have graduated successfully and on time. Here is a list of PhD students I have supervised in the last 5 years:

Main supervisor :

  • Ping Huang - (Marie Cure ETN "CaSR Biomedicine" - Developing CaSR-based therapeutics, calcilytics, for steroid-resistant asthma (2016-2019)
  • Bethan Mansfield (KESS2 PhD student) - Development of calcilytics for inflammatory lung disease (2018-current)
  • Kasope Wolffs - Role of the calcium-sensing receptor in the development of pulmonary fibrosis (2017-current)
  • Richard Bruce - Role of the calcium-sensing receptor in pulmonary remodelling (2017-current)
  • Petar Popov (Masters student)