20092020

Research output per year

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Personal profile

Research interests

I am exploring ways in which advances in gene editing can be used to treat human disease.

Our genes are coded by the DNA of every cell in our bodies and provide the instructions to make small molecules that allow each cell to function correctly for the task it performs. Several genes are involved in filling the inside of the eye with a watery liquid that provides nutrients to the lens and iris and maintain the overall shape. The same genes are used deep inside the brain to fill spaces inside the skull and spinal cord with a fluid called cerebrospinal fluid that cushions the brain and nervous system from physical damage and provides a conduit for nutrients that supports the growth and survival of nerves and their associated cells. The production of liquid for these purposes is tightly controlled and perfectly balanced with clearance mechanisms to ensure constant pressure.

Glaucoma describes a condition where the pressure inside the eye rises due to malfunction of these systems, eventually leading to damage to the nerves sending information about what you see to the brain and progressive blindness. A variety of current medications are available to lower pressure by limiting production of liquid inside the eye or increasing its drainage. These however are not a cure, require daily eye drops, and are associated with side effects such as blurred vision, itching or stinging. Hydrocephalus is a similar condition where the pressure inside the brain’s fluid system rises leading to brain damage and eventually, death. Current treatment generally involves an operation exposing the brain and inserting a shunt to drain the excess fluid out of the skull and reduce pressure. Nearly half of these devices become blocked needing replacement, or require repositioning, either of which add additional surgeries and more risk to the patient.

We are using the CRISPR/Cas9 system to make safe, programmed viruses capable of deleting the genes coding for small molecules responsible for moving water into both the eye and the brain. By deleting these molecules we block water import into these spaces, reduce the pressure and ultimately develop a new therapy for these conditions. As gene editing is permanent the ultimate goal is one injection that will cure these conditions rather than doing our best to manage the symptoms on a daily basis.

I am also interested in the mechanisms of action of the glucocorticoid hormones given as anti-inflammatory medication for various conditions. The brain and eye respond robustly to these hormones and disruption of their normal patterns and regulation have been widely linked to debilitating neuropsychiatric conditions such as post-traumatic stress disorder and major depression, while long-term glucocorticoid use in the eye is associated with the development of cataracts. By exploring the manner by which these hormone signal to cells we better understand how to target these drugs more effectively and without side effects.

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Research Output

  • 10 Article (Academic Journal)
  • 1 Chapter in a book
  • 1 Conference Abstract

Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA.

Pooley, J., Rivers, C. A., Kilcooley, M., Paul, S. N., Cavga, A. D., Kershaw, Y. M., Muratcioglu, S., Gursoy, A., Keskin, O. & Lightman, S. L., 10 Jan 2020, In : PLoS ONE. 15, 1, 35 p., e0227520.

Research output: Contribution to journalArticle (Academic Journal)

Open Access
File
  • 45 Downloads (Pure)

    Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 disruption using CRISPR-Cas9

    Wu, J., Bell, O. H., Copland, D. A., Young, A., Pooley, J. R., Maswood, R., Evans, R. S., Khaw, P., Ali, R. R., Dick, A. D. & Chu, C. J., 9 Jan 2020, In : Molecular Therapy. 10 p.

    Research output: Contribution to journalArticle (Academic Journal)

    Open Access
    File
  • 70 Downloads (Pure)

    Glucocorticoid Receptor-Tethered Mineralocorticoid Receptors Increase Glucocorticoid-Induced Transcriptional Responses

    Rivers, C. A., Rogers, M. F., Stubbs, F. E., Conway-Campbell, B. L., Lightman, S. L. & Pooley, J. R., 1 May 2019, In : Endocrinology. 160, 5, p. 1044-1056 13 p.

    Research output: Contribution to journalArticle (Academic Journal)

    Open Access
    File
  • 7 Citations (Scopus)
    167 Downloads (Pure)

    Prizes

    Best Basic Science Abstract (Society for Endocrinology BES Meeting 2015)

    Pooley, John R (Recipient), 4 Nov 2015

    Prize: Prizes, Medals, Awards and Grants

  • High Commended Oral Presentation (Society for Endocrinology BES Meeting 2015)

    Pooley, John R (Recipient), 4 Nov 2015

    Prize: Prizes, Medals, Awards and Grants