Staff Profile

Dr David Lewis-Smith is an Associate Clinical Lecturer and specialist registrar in neurology mentored by Dr Rhys H. Thomas at Newcastle University and Dr Ingo Helbig at Children's Hospital of Philadelphia, PA.

He has spent his Wellcome Trust Clinical PhD Research Training Fellow (4ward North Clinical PhD Academy) seeking to understand the effects of genetic factors on the clinical features of people's epilepsy and how knowledge of these relationships can facilitate precision medicine, personalising clinical care and treatment to a person's particular symptoms and disease mechanism.

His research focusses on the critical appraisal of phenotype in large collaborative genetic studies, using tools such as the Human Phenotype Ontology, to which he contributes. He develops computational methods to model the clinical reasoning that address the phenotypic bottleneck in large -omic projects, aiming to bridge the gap between clinical research and bioinformatics to bring people's symptoms to the centre of a platform data science approach.

He contributes to the International League Against Epilepsy (ILAE) internationally and nationally. He is junior leader of the Epilepsiome Task Force of the Genetics Commission, a member of the SNOMED Task Force of the Big Data Commission, Vice-chairperson of the British Chapter of the Young Epilepsy Section of the ILAE, and a member of the ClinGen Gene Expert Curation Panel for Epilepsy.

Dr David Lewis-Smith's reseach focusses on the computational analysis of epilepsy and associated neurological phenotypes to discover clinical and genetic biomarkers that will improve prognostication and treatment stratification for people with epilepsy.

His primary research tool is the Human Phenotype Ontology (HPO), to which he contributes. He works with research and electronic healthcare records, developing algorithms that model and formalise clinical reasoning to overcome the challenge of scalability (the phenotyping bottleneck) in modern multi-omic studies.

He has led the ILAE Epilepsiome Task Force's revision of the representation of seizures in the HPO in collaboration with Prof. Peter Robinson (Jackson Laboratory, CT).

He is privileged to work with data from the Epi25 Collaborative, UK Biobank, and other collaborative repositories. He contributes to the ILAE Consortium on Complex Epilepsies (common genetic variant analysis), the EU-funded Solve-Rare Disease WP1, and the NIH Center Without Walls Channopathy-associated Epilepsy Research Center led by Prof. Alfred L. George Jr. (Northwestern University, IL).

He presented his work as platform presentations at the American Epilepsy Society Annual Meeting 2020 and 2021 (Young Investigator Award) and the British ILAE Annual Scientific Meeting 2019 and 2021 (Clinical Presentation Prize), and invited to present at the American Academy of Neurology 2022.

Beyond epilepsy phenomics and genetics he collaborates with researchers in neurophysiology, developmental biology, and human brain connectome.

ORCID

Please do not hesitate to contact me if you wish to discuss potential collaboration.

Dr David Lewis-Smith is an Associate Fellow of the Higher Education Academy and offers teaching for medical students, junior doctors, general practitioners and psychiatrists in Newcastle upon Tyne.

• Articles

  • Montanucci L, Lewis-Smith D, Collins RL, Niestroj L-M, Parthasarathy S, Xian J, Ganesan S, Macnee M, Brünger T, Thomas RH, Talkowski M, Epi25 Collaborative, Helbig I, Leu C, Lal D. Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals. Nature Communications 2023, 14, 4392.
  • Daniali M, Galer PD, Lewis-Smith D, Parthasarathy S, Kim E, Salvucci DD, Miller JM, Haag S, Helbig I. Enriching representation learning using 53 million patient notes through human phenotype ontology embedding. Artificial Intelligence in Medicine 2023, 139, 102523.
  • Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, Chiesa V, Christensen J, Bernardina BD, Ellis CA, Furia F, Gardiner F, Giron C, Guerrini R, Klein KM, Korff C, Krijtova H, Leffner M, Lerche H, Lesca G, Lewis-Smith David, Marini C, Marjanovic D, Mazzola L, McKeownRuggiero S, Mochel F, Ramond F, Reif PS, Richard-Mornas A, Rosenow F, Schropp C, Thomas RH, Vignoli A, Weber Y, Palmer E, Helbig I, Scheffer IE, Striano P, Møller RS, Gardella E, Weckhuysen S. Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood. Neurology 2022, 99(3), e221-e233.
  • Elwan M, Fowkes R, Lewis-Smith D, Winder A, Baker MR, Thomas RH. Late-onset cluster seizures and intellectual disability associated with a novel truncation variant in SMC1A. Epileptic Disorders 2022, 19, 100556.
  • Stanley K, Hostyk J, Tran L, Dugan P, Clark J, Choi H, Perucca P, Fernandes C, Andrade D, Devinsky O, Cavalleri GL, Depondt C, Sen A, O'Brien T, Heinzen E, Loddenkemper T, Goldstein DB, Mikati MA, Delanty N, Adcock J, Andrade D, Brazil C, Cavalleri G, Choi H, Costello D, Delanty N, Depondt C, Dugan P, Goldstein D, Heinzen E, Lewis-Smith D, O'Brien T, Perucca P, Radtke R, Rees M, Sen A, Stanley K, Thomas R, Amengual-Gual M, Amengual-Gual M, Arya R, Agullar CB, Clark J, Fernandes C, Gainza-Lein M, Glauser TA, Goldstein D, Joshua L, Ann G, Lurie RH, Heinzen ME, Jackson, Tran L, Loddenkemper T, McDonough TL, Mikati MA, Peariso K, Fernandez IS, Sands T, Sheehan T, Stanley K, Tasker RC, Tchapyjnikov D, Tchapyjnikov D, Vasquez A, Wainright MS, Wilfong A, Williams K. Genomic analysis of “microphenotypes” in epilepsy. American Journal of Medical Genetics, Part A 2022, 188(1), 138-146.
  • Lewis-Smith D, Parthasarathy S, Xian J, Kaufman MC, Ganesan S, Galer PD, Thomas RH, Helbig I. Computational analysis of neurodevelopmental phenotypes: Harmonization empowers clinical discovery. Human Mutation 2022, 43(11), 1642-1658.
  • Lewis-Smith D, Jaiser SR, Thomas RH. Autoimmune musicogenic bilateral temporal lobe epilepsy. Epileptic Disorders 2022, 24(5), 961-964.
  • McLeod F, Dimtsi A, Marshall AC, Lewis-Smith DJ, Thomas R, Clowry GJ, Trevelyan AJ. Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy. Brain 2023, 146(3), 850-857.
  • Fowkes R, Elwan M, Akay E, Mitchell CJ, Thomas RH, Lewis-Smith D. A review of the clinical spectrum of BRAT1 disorders with addition of a developmental and epileptic encephalopathy with survival to adulthood. Epilepsy & Behavior Reports 2022, 19, 100549.
  • Kohler S, Gargano M, Matentzoglu N, Carmody LC, Lewis-Smith D, Vasilevsky NA, Danis D, Balagura G, Baynam G, Brower AM, Callahan TJ, Chute CG, Est JL, Galer PD, Ganesan S, Griese M, Haimel M, Pazmandi J, Hanauer M, Harris NL, Hartnett MJ, Hastreiter M, Hauck F, He Y, Jeske T, Kearney H, Kindle G, Klein C, Knoflach K, Krause R, Lagorce D, McMurry JA, Miller JA, Munoz-Torres MC, Peters RL, Rapp CK, Rath AM, Rind SA, Rosenberg AZ, Segal MM, Seidel MG, Smedley D, Talmy T, Thomas Y, Wiafe SA, Xian J, Yuksel Z, Helbig I, Mungall CJ, Haendel MA, Robinson PN. The Human Phenotype Ontology in 2021. Nucleic Acids Research 2021, 49(D1), D1207-D1217.
  • Lewis-Smith D, Ganesan S, Galer PD, Helbig KL, McKeown SE, O'Brien M, Khankhanian P, Kaufman MC, Gonzalez AK, Felmeister AS, Krause R, Ellis CA, Helbig I. Phenotypic homogeneity in childhood epilepsies evolves in gene-specific patterns across 3251 patient-years of clinical data. European Journal of Human Genetics 2021, 29, 1690-1700.
  • Lewis-Smith D, Galer PD, Balagura G, Kearney H, Ganesan S, Cosico M, O'Brien M, Vaidiswaran P, Krause R, Ellis CA, Thomas RH, Robinson PN, Helbig I. Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable. Epilepsia 2021, 62(6), 1293-1305.
  • Crawford K, Xian J, Helbig KL, Galer PD, Parthasarathy S, Lewis-Smith D, Kaufman MC, Fitch E, Ganesan S, O'Brien M, Codoni V, Ellis CA, Conway LJ, Taylor D, Krause R, Helbig I. Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders. Genetics in Medicine 2021, 23(7), 1263-1272.
  • Accogli A, Wiegand G, Scala M, Cerminara C, Iacomino M, Riva A, Carlini B, Camerota L, Belcastro V, Prontera P, Fernández-Jaén A, Bebek N, Scudieri P, Baldassari S, Salpietro VD, Novelli G, De Luca C, von Stülpnagel C, Kluger F, Kluger GJ, Wohlrab GC, Ramantani G, Lewis-Smith D, Thomas RH, Lai M, Verrotti A, Striano S, Depienne C, Minetti C, Benfenati F, Brancati F, Zara F, Striano P. Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy. Neurology 2021, 97(6), e577-e586.
  • Accogli A, Wiegand G, Scala M, Cerminara C, Iacomino M, Riva A, Carlini B, Camerota L, Belcastro V, Prontera P, Fernández-Jaén A, Bebek N, Scuderi P, Baldassari S, Salpietro VD, Novelli A, De Luca C, von Stulpnagel C, Kluger F, Kluger GJ, Wohlrag GC, Ramantani G, Lewis-Smith D, Thomas RH, Lai M, Verrotti A, Striano S, Depienne C, Minetti C, Benfenati F, Brancati F, Zara F, Striano P. Clinical and genetic features in patients with reflex bathing epilepsy. Neurology 2021, 97(6), e577-e586.
  • Galer PD, Ganesan S, Lewis-Smith D, McKeown SE, Pendziwiat M, Helbig KL, Ellis CA, Rademacher A, Smith L, Poduri A, Seiffert S, von Spiczak S, Muhle H, van Baalen A, NCEE Study Group, EPGP Investigators, EuroEpinomics Consortium, Genomics Research and Innovation Network, Thomas RH, Krause R, Weber Y, Helbig I. Semantic similarity analysis reveals robust gene-disease relationships in developmental and epileptic encephalopathies. American Journal of Human Genetics 2020, 107(4), 683-697.
  • Lewis-Smith DJ, Wolpe N, Ghosh BCP, Rowe JB. Alien limb in the corticobasal syndrome: phenomenological characteristics and relationship to apraxia. Journal of Neurology 2020, 267, 1147-1157.
  • Bansagi B, Lewis-Smith D, Pal E, Duff J, Griffin H, Pyle A, Müller JS, Rudas G, Aranyi Z, Lochmüller H, Chinnery PF, Horvath R. Phenotypic convergence of Menkes and Wilson disease. Neurology Genetics 2016, 2(6), e199.
  • Lewis-Smith DJ, Duff J, Pyle A, Griffin H, Polvikoski T, Birchall D, Horvath R, Chinnery PF. Novel HSPB1 mutation causes both motor neuronopathy and distal myopathy. Neurology: Genetics 2016, 2(2), e110.
  • Lewis-Smith D, Kamer KJ, Griffin H, Childs AM, Pysden K, Titov D, Duff J, Pyle A, Taylor RW, Yu-Wai-Man P, Ramesh V, Horvath R, Mootha VK, Chinnery PF. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood. Neurology: Genetics 2016, 2(2), e59.
  • Horvath R, Lewis-Smith D, Douroudis K, Duff J, Keogh M, Pyle A, Fletcher N, Chinnery PF. SCP2 mutations and neurodegeneration with brain iron accumulation. Neurology 2015, 85(21), 1909-1911.

• Book Chapter

  • Lewis-Smith D, Craig DP, Thomas NJP, Hamandi K, Thomas RH. Molecular genetic management of epilepsy. In: Clinical Molecular Medicine: Principles and Practice. Academic Press, 2020, pp.289-308.

• Conference Proceedings (inc. Abstracts)

  • Lewis-Smith D, Galer PD, Ganesan S, Krause R, Thomas RH, Helbig I, EpiCollaborative a. Ultra-rare Genetic Variants Influence Clinical Features of the Epilepsies. In: American Epilepsy Society Annual Meeting. 2021, Virtual: American Epilepsy Society.
  • Lewis-Smith D, Balagura G, Kearney H, Galer P, Ganesan S, Gan G, Krause R, Robinson P, Helbig I. When 'seizure' won’t cut the mustard - Explaining the relationship between different seizures to non-specialists and computers for algorithmic interpretation. In: International League Against Epilepsy British Branch Annual Scientific Meeting. 2019, Birmingham: ILAE.
  • Kearney H, Lewis-Smith D, Balagura G, Ganesan S, Galer PD, Gan J, Wang Y, Kiat NTC, Lench NJ, Steward CA, Krause R, Robinson P, Delanty N, Cavalleri G, Helbig I. The Epilepsiome project: Revising the Human Phenotype Ontology for epilepsy and seizure. In: American Epilepsy Society Annual Meeting. 2019, Baltimore: American Epilepsy Society.
  • Lewis-Smith D, Craig D, Thomas RH. The adult phenotypes of paediatric-onset genetic epilepsies. In: Association of British Neurologists Annual Meeting. 2019, Edinburgh: BMJ Publishing.
  • Hagan A, Lewis-Smith D, Thomas RH. Analysis of pedigree structure on epilepsy families: a global review. In: International League Against Epilepsy British Branch Annual Scientific Meeting. 2018, Birmingham: ILAE.
  • Lewis-Smith DJ, Patil B, Ramesh V, Chinnery PF, Basu AP. Biotin-Thiamine-Responsive Basal Ganglia Disease: A Rare But Treatable Cause Of Severe Necrotising Encephalopathy. In: British Paediatric Neurology Association Annual Meeting. 2017, Cambridge, UK: Wiley-Blackwell.
  • Bolton C, Chapman J, Ledingham D, Lewis-Smith D, Spyropoulos A, Guadagno J, Duddy M. The Newcastle Experience of Anti-Mog Associated Disease. In: ABN Annual Meeting. 2016, Brighton, UK: BMJ Publishing Group.
  • Lewis-Smith D, Basu A, Hussain R, Patil B, Ramesh V, Chinnery PF. Repeated dramatic reversal of thiamine-responsive necrotising encephalopathy due to SLC19A3 mutations emphasises the importance of considering vitamin-responsive pathologies in acute neurology. In: 2nd Congress of the European Academy of Neurology. 2016, Copenhagen: Wiley-Blackwell.
  • Childs AM, Pysden K, Roper H, Chow G, Niks EH, Kriek M, Chinnery PF, Lewis-Smith D, Duchen M, Szabadkai G, Logan C, Sheridan E, Sewry C, Muntoni F. Clinical and pathological features associated with mutations in MICU1. In: 19th International Congress of The World Muscle Society. 2014, Berlin, Germany: Elsevier.
  • Lewis-Smith DJ, Ghosh BCP, Rowe JB. The alien limb syndrome of corticobasal degeneration is both common and independent of apraxia. In: Joint Meeting of the Association of British Neurologists and Sociedad Cubana de Neurología y Neurocirugía. 2011, Havana: BMJ Publishing: Journal of Neurology, Neurosurgery and Psychiatry. In Preparation.

• Letters

  • Lewis-Smith D, Thomas RH. The prevalence of genetically diagnosable epilepsies in young adulthood: How many should we be looking for?. Epilepsia 2020, 61(9), 2053-2054.
  • Lewis-Smith D, Ellis CA, Helbig I, Thomas RH. Early-onset genetic epilepsies reaching adult clinics. Brain 2020, 143(3), e19.

• Review

  • Gulcebi MI, Bartolini E, Lee O, Lisgaras CP, Onat F, Mifsud J, Striano P, Vezzani A, Hildebrand MS, Jimenez-Jimenez D, Junck L, Lewis-Smith D, Scheffer IE, Thijs RD, Zuberi SM, Blenkinsop S, Fowler HJ, Foley A, Sisodiya SM, Balestrini S, Berkovic S, Cavalleri G, Correa DJ, Martins Custodio H, Galovic M, Guerrini R, Henshall D, Howard O, Hughes K, Katsarou A, Koeleman BPC, Krause R, Lowenstein D, Mandelenaki D, Marini C, O'Brien TJ, Pace A, De Palma L, Perucca P, Pitkanen A, Quinn F, Selmer KK, Steward CA, Swanborough N, Thijs R, Tittensor P, Trivisano M, Weckhuysen S, Zara F. Climate change and epilepsy: Insights from clinical and basic science studies. Epilepsy and Behavior 2021, 116, 107791.