麻豆传媒

Wellcome Trust Career Re-Entry Fellow

I am a biomedical/life scientist with expertise in Physiology, Pharmacology and Biophysics, working in pre-clinical and translational setting. I have obtained BSc degree in Biology, MSc degree in Biophysics, and PhD in Pharmacology. Since obtaining my PhD, I worked at the University of Oxford, King’s College London, and Cardiff University, focussing my research on G protein-coupled receptors signalling in the airways, cardiovascular system, and neurodegenerative disorders. I have developed a particular interest in cation sensor, CaSR, signalling in health and disease. My work has led to a discovery that targeting CaSR-based signalling mechanisms can prevent airways hyperresponsiveness and inflammation, which may become a novel therapeutic strategy aimed to combat asthma and COPD. I am a winner of several awards, including the Wellcome Trust Career Re-Entry Fellowship designed to investigate the roles of CaSR in the development of nosocomial infections in critical illness. Data collected from critically ill patients, healthy volunteers, in vitro and in vivo models of acute lung inflammation will provide the most comprehensive assessment of polycation regulation in human lung to date, and potentially suggest new pharmacological strategies to explore with a view of preventing immune dysfunctions in critical illness.

ORCID: 0000-0002-7534-7995 

https://www.researchgate.net/profile/Polina-Yarova

Extracellular polycation signalling in alveolar and systemic inflammation

My scientific interest covers all aspects of polycation signalling, spanning from a single molecule structure and function to pre-clinical and translational research, including disease modelling and work with patient samples. Currently, I investigate roles of cation sensor in critical illness, specifically, the way it regulates inflammation and immune dysfunction in intensive care patients. This important work opens new horizons of patient management and antibiotic stewardship and may provide novel avenues for prevention and treatment of hospital-acquired infections.

Polycations are positively charged molecules such as di-, tri-valent cations, polyamines, and polycationic peptides. Their extracellular concentrations can vary dramatically in health and disease. A cation sensor, namely CaSR, can recognise changes in concentrations of various polycationic molecules in the environment and translate these changes into intracellular signalling cascades. Apart of maintaining extracellular calcium homeostasis, it becomes widely recognised that CaSR plays an important role in the development of inflammation and hyperresponsiveness. I made a major contribution in revealing the pathophysiological roles of CaSR in development of chronic pro-inflammatory lung disease such as asthma, now I am investigating its roles in acute lung inflammation as such seen in ventilator-associated pneumonia and sepsis.

In order to investigate polycation signalling in the most appropriate setting, I am employing and further developing various in vitro, ex vivo and in vivo models. Our laboratory is routinely testing samples obtained from healthy volunteers and intensive care unit patients. When necessary, in vivo models of acute or chronic lung disease can be employed. Being a keen adept of ethical research, I am moving towards replacing animal models with animal-friendly and human-relevant 3D models of tissues developed from human primary and induced pluripotent stem cells with the aim to design multisystem in vitro models relevant to lung disease and critical illness.

I am also developing the following additional paths of my research:

1. In vitro and in vivo lung disease modelling, including stem-cells derived ALI pneumonia model with the aim to streamline pre-clinical drug discovery from cells to 3D iPSC-derived lung models and co-cultures with relevant tissues obtained from specific patients as a path to personalised medicine of the future.
2. Investigating cross-talk between severe infections in critical care settings and short- and long-term brain dysfunction such as septic encephalopathy. There is a pressing need to understand the pathophysiology of this condition to help developing treatment strategies.
3. Testing novel compounds in lung fibrosis models, with a particular focus in idiopathic pulmonary fibrosis, a devastating condition to which currently there is no cure. Obtained results may help treating other pro-inflammatory conditions that lead to fibrotic lung remodelling, such as asthma and chronic obstructive pulmonary disease.

I work in close collaboration with experts from clinical, translational, and basic science fields, within the UK and internationally, developing strong ties with industrial partners in parallel. This approach facilitates research of our group to help bringing novel therapies from bench to bedside in the most efficient way.

• Supervision of project and summer placement of biomedical, dental and pharmacy students of both under- and postgraduate levels;
• Respiratory course lead for Dent students;
• Teaching Stage 1 seminars in Cell Singalling;
• Tutoring FMS MRes students;

I hold NU Associate Fellow status.

• Articles

  • Chuinsiri N, Siraboriphantakul N, Kendall L, Yarova P, Nile CJ, Song B, Obara I, Durham J, Telezhkin V. . British Journal of Pharmacology 2024, 181(15), 2676-2696.
  • Liu Q, Telezhkin V, Jiang W, Gu Y, Wang Y, Hong W, Tian W, Yarova P, Zhang G, Lee SM-Y, Zhang P, Zhao M, Allen ND, Hirsch E, Penninger J, Song B. . Cell and Bioscience 2023, 13(1), 4.
  • Yarova PL, Huang P, Schepelmann MW, Bruce R, Ecker R, Nica R, Telezhkin V, Traini D, dos Reis LG, Kidd EJ, Ford WR, Broadley KJ, Kariuki BM, Corrigan CJ, Ward JPT, Kemp PJ, Riccardi D. . Journal of Pharmacology and Experimental Therapeutics 2021, 376(1), 51-63.
  • Telezhkin V, Straccia M, Yarova P, Pardo M, Yung S, Vinh N-N, Hancock JM, Barriga GG-D, Brown DA, Rosser AE, Brown JT, Canals JM, Randall AD, Allen ND, Kemp PJ. . Pflugers Archiv European Journal of Physiology 2018, 470, 1359-1376.
  • Yarova PL, Davies C, Price SA, Huang Q, Graca JA, Maleki-Toyserkani S, Lowe APP, Kidd EJ, Ford WR, Broadley KJ, Ward JPT, Corrigan CJ, Prakash YS, Kemp PJ, Riccardi D. . Respiratory Drug Delivery 2016, 1(1), 1-12.
  • Kemp PJ, Rushton DJ, Yarova PL, Schnell C, Geater C, Hancock JM, Wieland A, Hughes A, Badder L, Cope E, Riccardi D, Randall AD, Brown JT, Allen ND, Telezhkin V. . The Journal of Physiology 2016, 594(22), 6583-6594.
  • Telezhkin V, Schnell C, Yarova P, Yung S, Cope E, Hughes A, Thompson BA, Sanders P, Geater C, Hancock JM, Joy S, Badder L, Connor-Robson N, Comella A, Straccia M, Bombau G, Brown JT, Canals JM, Randall AD, Allen ND, Kemp PJ. . American Journal of Physiology - Cell Physiology 2016, 310(7), C520-C541.
  • Yarova PL, Stewart AL, Sathish V, Britt RD, Thompson MA, Lowe APP, Freeman M, Aravamudan B, Kita H, Brennan SC, Schepelmann M, Davies T, Yung S, Cholisoh Z, Kidd EJ, Ford WR, Broadley KJ, Rietdorf K, Chang W, Bin Khayat ME, Ward DT, Corrigan CJ, Ward JPT, Kemp PJ, Pabelick CM, Prakash YS, Riccardi D. . Science Translational Medicine 2015, 7(284), 284ra58.

• Review

  • Riccardi D, Ward JPT, Yarova PL, Janssen LJ, Lee TH, Ying S, Corrigan CJ. . European Respiratory Journal 2022, 60(2), 2102103.