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Wolfson Institute for Biomedical Research

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Dr Andrei L. Okorokov

GENE REGULATION AND PAIN

Andrei

Tel: 020 7679 0959

Email: a.okorokov@ucl.ac.uk

IRIS: https://iris.ucl.ac.uk/iris/browse/profile?upi=AOKOR60


Pain is a major clinical problem and affects more people than diabetes, heart disease and cancer combined. Pain is a cofactor in many medical conditions yet pain medicines are often only partially effective, and the problem is increasing with an aging population. By understanding the cellular and molecular processes that lead to the sensation of pain, more effective targeted therapies can be developed to alleviate suffering.

After two decades of work in transcriptional control of tumour suppression (p53 field) and DNA replication, I am now working (in collaboration with Prof. James Cox) on a new research direction into the transcriptional and post-transcriptional regulation of pain pathways and sensory circuits connected to mental health.

We recently reported two new genes for human pain insensitivity which, interestingly, also have direct links to depression. Thus, ZFHX2 Marsili syndrome transcription factor, is a gene that is linked to enhanced depression-like behaviours in knockout mice. The second, FAAH-OUT, is a long non-coding RNA (lncRNA) that regulates the expression of FAAH, a key enzyme in the endocannabinoid system. Loss-of-function of FAAH-OUT (in humans) and of FAAH (in mice) results in reduced depression, fear and anxiety, highlighting the importance of the endocannabinoid system and its downstream regulated genes to mental health states.

Our current focus is to (i) elucidate the molecular network that connects the endocannabinoid system to regulation of pain, wound-healing and mood states and (ii) translate these findings into future treatments for pain, anxiety and depression.


Publications

Mikaeli H et al., (2023) Molecular basis of FAAH-OUT-associated human pain insensitivity. Brain  doi: 10.1093/brain/awad098

Habib AM et al., (2019)  Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. Br J Anaesth.123(2):e249-e253. doi: 10.1016/j.bja.2019.02.019

Habib AM et al., (2018) A novel human pain insensitivity disorder caused by a point mutation in ZFHX2. Brain 141(2):365-376  doi: 10.1093/brain/awx326