A5048202457- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Pediatric Pain Management Techniques
- Herpesvirus Infections and Treatments
- Neuroscience and Neuropharmacology Research
- Botulinum Toxin and Related Neurological Disorders
- Metabolism and Genetic Disorders
- Urinary Bladder and Prostate Research
- Health, Environment, Cognitive Aging
- Genetic Associations and Epidemiology
- Nutrition, Genetics, and Disease
- Genomics and Rare Diseases
- Healthcare and Venom Research
- Genital Health and Disease
- Hair Growth and Disorders
- RNA and protein synthesis mechanisms
- Pediatric health and respiratory diseases
- Lipid Membrane Structure and Behavior
University of Cambridge
2018-2024
Yale University
2022-2023
Center for Neuroscience and Regenerative Medicine
2022-2023
VA Connecticut Healthcare System
2022-2023
Addenbrooke's Hospital
2017
Wellcome Trust
2017
PRDM12 polyalanine tract expansions cause two different disorders: midfacial toddler excoriation syndrome (MiTES; itch with normal pain sensation associated 18 homozygous alanines (18A); and congenital insensitivity to (CIP) 19 (19A). Knowledge of the phenotype, genotype disease mechanism MiTES is incomplete. Why 18A vs. 19A can almost opposite phenotypes unknown; no other or polyglutamine expansion causes such disparate phenotypes.
Neuronal excitability relies on coordinated action of functionally distinction channels. Voltage-gated sodium (Na<sub>V</sub>) and potassium (K<sub>V</sub>) channels have distinct but complementary roles in firing potentials: Na<sub>V</sub> provide depolarizing current while K<sub>V</sub> hyperpolarizing current. Mutations dysfunction multiple underlie disorders excitability, including pain epilepsy. Modulating ion channel trafficking may offer a potential therapeutic strategy for these...
Midface toddler excoriation syndrome (MiTES) is a condition recently reported in three unrelated children. Habitual scratching from the first year of life inflicted deep, chronic, scarring wounds around nose and eyes. One child had mild neurological deficit but there was no other evidence insensitivity to pain. Bilateral distribution localization midface distinguish MiTES causes self-inflicted skin damage such as trigeminal trophic syndrome. An earlier study five siblings consanguineous...
Non-addictive treatment of chronic pain represents a major unmet clinical need. Peripheral voltage-gated sodium (Na V ) channels are an attractive target for therapy because they initiate and propagate action potentials in primary afferents that detect transduce noxious stimuli. Na 1.7 sets the gain on peripheral pain-signaling neurons is best validated ion channel involved human pain, previous work has shown it transported vesicles sensory axons which also carry Rab6a, small GTPase known to...
Significant human diseases/phenotypes exist which require both an environmental trigger event and a genetic predisposition before the disease/phenotype emerges, e.g. Carbamazepine with rare SNP allele of rs3909184 causing Stevens Johnson syndrome, aminoglycosides rs267606617 sensory neural deafness. The underlying genotypes are fully penetrant only when correct trigger(s) occur, otherwise they silent harmless. Such will not appear to have Mendelian inheritance pattern, unless is very common...
中面部幼儿剥脱综合征 (MiTES) 是一种新被认识的疾病, 在此病中, 表面健康儿童持续搔抓鼻梁中央的局部面部。这一问题在出生后第一年开始, 导致深在伤口和严重瘢痕。这可能易被误认为虐待儿童。此病的原因不明, 但一篇发表于 2015 年的论文提供了线索, 这篇论文描述了 11 个对疼痛先天不敏感家庭, 这些家庭在一个新认识的名为 PRDM12 的基因存在突变, 该基因负责编码疼痛受体神经发生必须的一种蛋白。大部分 突变患者的肢体发生切断性伤害, 因为他们缺乏避免伤害的疼痛反应。但是, 个家庭中有一个受到的伤害较轻, 5 名受影响的兄弟姐妹存在一种被描述为“鼻周搔抓”的疾病(与 MiTES 看起来相同)。因此, 来自英国、印度和爱尔兰团队分析了 例新发 病例中的PRDM12。4 名儿童, 其中 2 名为手足, 存在与在早期报告中相同的 的突变, 但在第 名儿童中未见任何突变。在大多数病例中, 父母有亲属关系, 在一个基因上携带突变, 而受影响儿童的两个基因均受到影响。这项研究证实 为一种遗传性疾病, 在某些情况下因...
Mid‐face Toddler Excoriation Syndrome (MiTES) is a newly recognised condition in which apparently healthy children persistently scratch their faces localised area centred on the bridge of nose. The problem starts first year life and results deep wounds severe scarring. It can easily be mistaken for child abuse. cause was unknown, but clue came from paper published 2015 describing 11 families with congenital insensitivity to pain who had mutations gene called PRDM12, codes protein essential...