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  • Please visit the Pure Research Information Portal for further information
  • A multinational Delphi consensus to end the COVID-19 public health threat, Lazarus, J., Romero, D., Kopka, C., Karim, S., Abu-Raddad, L., Almeida, G., Baptista-Leite, R., Barocas, J., Barreto, M., Bar-Yam, Y., Bassat, Q., Batista, C., Bazilian, M., Chiou, S., Del Rio, C., Dore, G., Gao, G., Gostin, L., Hellard, M., Jimenez, J., Kang, G., Lee, N., Matičič, M., McKee, M., Nsanzimana, S., Oliu-Barton, M., Pradelski, B., Pyzik, O., Rabin, K., Raina, S., Rashid, S., Rathe, M., Saenz, R., Singh, S., Trock-Hempler, M., Villapol, S., Yap, P., Binagwaho, A., Kamarulzaman, A., El-Mohandes, A., Moschos, S. 10 Nov 2022, In: Nature
  • Bacterial Adaptation to Venom in Snakes and Arachnida, Esmaeilishirazifard, E., Usher, L., Trim, C., Denise, H., Sangal, V., Tyson, G., Barlow, A., Redway, K., Taylor, J., Kremyda-Vlachou, M., Davies, S., Loftus, T., Lock, M., Wright, K., Dalby, A., Snyder, L., Wuster, W., Trim, S., Moschos, S. 29 Jun 2022, In: Microbiology spectrum
  • Beyond GalNAc! Drug delivery systems comprising complex oligosaccharides for targeted use of nucleic acid therapeutics, O'Sullivan, J., Muñoz-Muñoz, J., Turnbull, G., Sim, N., Penny, S., Moschos, S. 14 Jul 2022, In: RSC Advances
  • The Idiopathic Pulmonary Fibrosis-associated single nucleotide polymorphism rs35705950 is transcribed in a MUC5B Promoter Associated Long Non-Coding RNA (AC061979.1), Neatu, R., Enekwa, I., Thompson, D., Schwalbe, E., Fois, G., Abdelaal, G., Veuger, S., Frick, M., Braubach, P., Moschos, S. 30 Nov 2022, In: Non-coding RNA
  • The Idiopathic Pulmonary Fibrosis-Associated SNP rs35705950 Is Transcribed in a MUC5B Promoter Associated Long Non-Coding RNA (AC061979.1), Enekwa, I., Neatu, R., Fois, G., Frick, M., Moschos, S. 1 May 2022, In: American Journal of Respiratory and Critical Care Medicine
  • A new threat from an old enemy: Re-emergence of coronavirus (Review), Docea, A., Tsatsakis, A., Albulescu, D., Cristea, O., Zlatian, O., Vinceti, M., Moschos, S., Tsoukalas, D., Goumenou, M., Drakoulis, N., Dumanov1, J., Tutelyan, V., Onischenko, G., Aschner, M., Spandidos, D., Calina, D. Jun 2020, In: International Journal of Molecular Medicine
  • Bioengineering bacterial outer membrane vesicles as delivery system for RNA therapeutics targeted to lung epithelial cytosols, Eftychiou, E., Brown, N., Cheung, W., Fois, G., Frick, M., Moschos, S. 12 May 2020, ASGCT 23rd Annual Meeting
  • Comprehensive Analysis of Drugs to Treat SARS‑CoV‑2 Infection: Mechanistic Insights Into Current COVID‑19 Therapies (Review), Nitulescu, G., Paunescu, H., Moschos, S., Petrakis, D., Nitulescu, G., Ion, G., Spandidos, D., Nikolouzakis, T., Drakoulis, N., Tsatsakis, A. Aug 2020, In: International Journal of Molecular Medicine
  • Measuring the action of oligonucleotide therapeutics in the lung at the cell type specific level by Tissue Disruption and Cell Sorting (TDCS): In vivo cell type-specific oligonucleotide PK/PD, Graves, H., Evans, S., Fauler, M., Frick, M., Moschos, S. 2019, Oligonucleotide-based Therapies, New York, NY, Springer
  • Predicting oligonucleotide therapeutic efficacy at the population level, Theotokis, P., Usher, L., Kortschak, C., Schwalbe, E., Moschos, S. 1 Nov 2019, In: Hellenic Journal of Nuclear Medicine

  • Eleni Eftychiou Bioengineering Outer Membrane Vesicles as Delivery Systems for Biotherapeutics Targeted to Lung Epithelial Cytosols Start Date: 01/10/2017 End Date: 16/12/2021
  • Ifeanyi Enekwa Single Transcriptional Unit Gene-Editing for Inheritable Lung Disease Start Date: 01/02/2018
  • Joseph O'Sullivan RESOLVING THE INTRACELLULAR MOLECULAR THERAPY BOTTLENECK FOR AIRWAYS DISEASE Start Date: 15/10/2018

  • PhD October 01 2004
  • Molecular Biology BSc (Hons) July 10 1999
  • Fellow (FHEA) Higher Education Academy (HEA) 2017
  • Fellow Institute of Biomedical Science (IBMS) 2015
  • Fellow (FRSC) Royal Society of Chemistry (RSC) 2014
  • Full Member Genetics Society 2012
  • Full Member Biochemical Society 2005
  • Full Member Society for General Microbiology (SGM) 1998

BreatheIN: Principal Investigator

Gene therapy has come to the forefront of personalized molecular medicine since the regulatory approval of new oligonucleotide therapeutics for systemic and neuromuscular diseases (e.g. the antisense and exon skipping mipomersen, nusinersen, & eteplirsen), and viral gene therapies for inherited diseases and cancer (alipogene tiparvovec, strimvelis, kymriah). More recently, the first positive phase III clinical trial data have been published for RNA Interference (RNAi) drugs, suggesting a first regulatory approval in early 2018.

Although there is great unmet need for lung disease (e.g. severe asthma, emphysema, cystic fibrosis, alpha 1 antitrypsin deficiency, pulmonary fibrosis, viral infections, bronchiolitis obliterans, etc.), we have shown that oligonucleotide therapies do not work in the airways, but they can reach and work in the liver and kidney if inhaled. Solutions involving GM viruses or virus-like nanotechnology do work, but are dangerous for patients whose well-being is at risk from the pro-inflammatory effect of such nanoparticles.

We are working on basic and applied research to understand the function of airway cell receptors, to select amongst them appropriate molecular targets and their ligands, that will allow effective internalization of molecular therapy cargoes such as antisense, siRNA, miRNA, CRISP/CAS gene editing systems, and protein therapeutics. We are currently pursuing a biological and a small molecule chemical compound as simple, chemical conjugation-based, candidate solutions.

Predictive Pharmacogenomics: Principal Investigator

Most gene therapies involve the targeting of genes who are functioning improperly: too much gene expression, erroneous RNA processing (splicing), or mutations that stop the function of molecules key to normal cell biology. Many of these gene therapies, such as small interfering RNA, RNase H-active antisense, and gene editing tools such as CRISPR-CAS, function by identifying their molecular targets using Watson-Crick base pairing and then cutting them at a specific position. However, in many cases other, potentially dangerous, bodily responses can have the same net effect that might look like the drug is working.

In 2014 we were the first to develop a big data method that can measure digitally the effect and precision of target-cleaving molecular drugs. In 2017, we published a development of this method that combines viral genomics, genetic engineering, and big data analytics that can be used to measure the pharmacological effect of any single nucleotide variation/polymorphism in a gene targeted by cleaving molecular drugs.

This means that a simple, single cell culture experiment can now be used to assess which patients will benefit from such a drug, and by how much, before starting animal experiments or clinical trials. As a result, drugs can be therefore tested and later prescribed to patients in which they will work. We are working on advancing this technology to a single, bench-to-bedside test that can choose patients for treatment, predict drug response, quantify actual drug effect and monitor resistance evolution (important for cancer).

PULMOSCREEN: Principal Investigator and co-inventor

Our breath carries enormous amount of information regarding our well-being: from the number of drinks we’ve had on a night out, to information about the state of our liver or the extent of injury in our lungs. Whilst some technologies can help measure one or two molecules (e.g. breath alcohol), basic research and further expansion of this area is hampered by the unavailability of devices that can be operated reliably, reproducibly, and anywhere this might be necessary. We are addressing this market gap through a new breath sampling platform that is helping us understand the dynamics of the lung as a environment for microorganisms, and how these influence disease states (WestFocus PARK funding).

EBOLACHECK: r2hc, £620,000, Nov 2014-2015, Principal Investigator

The West African Ebola virus outbreak between 2014-2016 clearly articulated the need to take genetic testing out of the lab and into the field, be it the pharmacy, the airport terminal or the straw hut in rural Africa. To achieve this specifically for Ebola virus detection and quantification, I formed a team spanning three continents, two biotech companies and the biggest responders to the crisis, Public Health England and the United States Army Medical Research Institute for Infectious Diseases. Within 15 months, we took a sketch idea to a fully functional system and test, suited for use at the frontline of healthcare, with minimal training, up to 8 times faster, and at a cost relevant to the most affected nations.

By going back to basics and understanding the ground truths, the resulting QuRapID platform can detect and measure the genome of Ebola virus in a drop of blood from patients exhibiting the symptoms of the disease, as reliably as clinical molecular laboratory testing. The technology is now under further development for use in pre-symptomatic patients and for the detection of other infectious diseases where the levels of pathogen might be much lower than Ebola. We are exploring this point of need technology for uses in other neglected tropical diseases and conditions where fast, low-cost genetic diagnosis might be an advantage, such as meningitis

  • Dr Fatemeh Momen-Heravi
  • Dr Joe Taylor
  • Dr Elham Ishmaelishirazifard
  • Mr Kavit Shah
  • Mr Pantazis Theotokis
  • Miss Alina Ozuna
  • Mrs Marta Fracszsak
  • Mr Declan Gardner
  • Miss Amie Wilkinson
  • Miss Anna-Maria Gudmundsdottir
  • Miss Myrto Kremmyda-Vlachou
  • Mr Sufyan Maqbool
  • Mr Kiran Dedhia

Shah K., Bentley, E., Tyler A., Richards K.S., Wright, E., Easterbrook, L., Lee, D., Cleaver, C., Usher, L.,1 Burton J.E., Pitman, J.K., Bruce C.B., Edge, D., Lee, M., Nazareth, N., Norwood, D.A., and Moschos S.A. Field-deployable, Quantitative, Rapid Identification of Active Ebola Virus Infection in Unprocessed Blood. Chemical Science, 2017, 8(11): 7780-7797 (IF: 8.688).

Theotokis, P. Kortschak, C., & Moschos, S.A. Profiling the Mismatch Tolerance of Argonaute 2 through Deep Sequencing of Sliced Polymorphic Viral RNAs. Molecular Therapy Nucleic Acids, 15(9):22-33 (IF: 6.392).

Moschos, S.A, Usher, L., & Lindsay M.A. Clinical potential of oligonucleotide-based therapeutics in the respiratory system. Pharmacology & Therapeutics, 2017, 169:83-103 (IF: 11.000)

Denise, H., Moschos, S.A., Sidders, B., Burden, F., Perkins, H., Carter, N., Stroud, N., Kennedy, M., Fancy, S.-A., Lapthorn, C., Lavender, H., Kinloch, R., Suhy, D. & Corbau, R. Deep sequencing insights in therapeutic shRNA processing & siRNA target cleavage precision. Mol. Ther. Nucleic Acids, 2014, 3:e145. (IF: 6.392).

Moschos, S.A., Frick, M., Taylor, B., et al. Uptake, efficacy & systemic distribution of naked, inhaled short interfering RNA (siRNA) & locked nucleic acid (LNA) antisense. Mol. Ther. 2011, 19(12):2163-8. (IF: 6.668)

Tsitsiou, E., Williams, A.E., Moschos, S.A., Jiang, X., Adams, O.D., Patel, K., Macedo, P., Woodcock, A., Fidock, M., Chung, K.F., & Lindsay, M.A. Transcriptome analysis show activation of circulating CD8+ T-cells in patients with severe asthma, J. Allergy Clin. Immunol. 2011, 129(1):95-103. IF: 12.485 

Key Publications

NRL Link

  • Scientific advisory board member to 2 undisclosed private biotechnology companies.
  • Scientific advisory board member to 2 undisclosed biotherapeutics venture funds.
  • Scientific advisory board member to three industry-focused, commercial conference organisations.
  • Active member of 15 learned societies.
  • Regularly reviews on 8 leading journals including the Molecular Therapy, Lancet and Nucleic Acids Research journal families.
  • Leader of the Northumbria University iGEM group.
  • External Examiner, MSc Biochemistry, Kingston University.
  • Reviewer for grants submitted to RCUK (BBSRC, MRC, EPSRC), Wellcome Trust, GIF, HIF, ELRHA.

Sterghios is an RNA biologist with specific interest in Personalised Medicine and Gene Therapy. His work explores innovative ways by which RNA and big data can be used to better understand disease, measure with high accuracy and precision what happens to the patient, and use systems approaches to intervene optimally, eliminating the cause of disease where possible. 

To meet these challenges, work in the Moschos lab is equally divided between bioanalytical innovation and overcoming the greatest bottleneck in molecular therapy with nucleic acid drugs: delivery. This is achieved by training multidisciplinary scientists on cutting edge biomedicine that integrates the latest computational, engineering and biotechnological advances in their work. The goal of his team is to perform industrial-grade orthogonal research, delivering highly reliable basic and applied outputs that transform the field, enable leap advances in diagnostics and therapeutics research, and ultimately revolutionise healthcare provision.

Working on gene therapies such as genome editing, RNAi (siRNA, miRNA), antisense and IVT-RNA, his group is exploring airway epithelial receptor systems for targeted intracellular delivery of nucleic acid drugs. This includes establishing a dedicated biomedical resource facility for receptor characterisation and ligand screening in 3D lung organoids, and the development of proprietary chemical and biological receptor-mediated delivery ligands. Furthermore, the team is working on patent-protected innovations around non-invasive deep lung molecular analytics, as well as advanced diagnostic-compatible methods suited to patient selection and stratification for gene therapy.

With over a decade of experience working with government and commercial organisations in the UK, USA, China, Japan, Korea and Australia, Sterghios is available globally for contract research, expert testimony and consultancy services. Such contracts have so far covered RNA Rx/Dx research, Biology-related information technology, biotech investment and intellectual property protection/analysis.

Active Collaborations

  • Prof. Manfred Frick, University of Ulm, Germany.
  • Prof. Jochen Lennerz, Harvard Medical School, MA, USA.
  • Prof. John Simpson, Newcastle University.
  • Prof. Justin Perry, Northumbria University.
  • Dr. Gary Black, Northumbria University.
  • Dr. Darren Smith, Northumbria University.
  • Dr. Vartul Sangal, Northumbria University.
  • Dr. Ed Schwalbe, Northumbria University.
  • Dr. William Chang, Northumbria University.
  • Dr. Fatemeh Momen-Heravi, Columbia University, NY, USA
  • Dr. Sebastian Oltean, University of Exeter
  • Dr. Uwe Mammat, Research Centre Borstel, Germany.
  • Dr. Ed Wright, University of Sussex.
  • Dr. Carol Trim, Canterbury University.
  • Dr. Wolfgang Wuster, Bangor University.
  • Dr. Lori Snyder, Kingston University.
  • Dr. Manish Kumar, EMBL Monterotondo, Italy.
  • Mr. Steve Trim, Venomtech Ltd. 

Previous Collaborations

  • Prof. Randy Mrsny, University of Bath
  • Prof. Myron Christodoulides, University of Southampton
  • Dr. David A. Norwood, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
  • Dr. Kevin Richards, Public Health England Porton Down.
  • Dr. Hubert Denise, EMBL-EBI, Cambridge.
  • Dr. Sue Cotterill, St. George’s University of London.
  • Dr. Alex Yaw Debrah, Kwame Nkrumah University of Science and Technology, Ghana.
  • Dr. Clement Opoku Okrah, Kwame Nkrumah University of Science and Technology, Ghana.
  • Dr. Camilla Benfield, Royal Veterinary College.
  • BioGene Ltd., Cambridge.
  • BG Research Ltd., Cambridge.
  • Benitec Biopharma, Melbourne, Australia.
  • Pfizer Global Research and Development, Sandwich, Kent.

 

 

Past Sponsors

  • R2HC
  • ELRHA
  • The Wellcome Trust
  • Department for International Development
  • Defence Science and Technology Laboratories
  • BBSRC
  • MRC
  • Asthma UK
  • GSK
  • Sanofi Aventis
  • Locus Genetics LLC.
  • Caliper Life Sciences
  • Miltenyi Botech

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