Shushu Huang, MD, PhD
Associate Research Scientist in GeneticsCards
About
Research
Publications
2024
High-throughput assays to assess variant effects on disease
Ma K, Gauthier L, Cheung F, Huang S, Lek M. High-throughput assays to assess variant effects on disease. Disease Models & Mechanisms 2024, 17: dmm050573. PMID: 38940340, PMCID: PMC11225591, DOI: 10.1242/dmm.050573.Peer-Reviewed Original ResearchConceptsDeep mutational scanningGenetic variantsRare disease diagnosticsRare genetic variantsDisease mechanismsHigh-throughput assaySequencing effortsInvestigation of variantsMutational scanningModel cell lineVariant effectsMolecular toolsCell linesCell survival rateFunctional assaysDrug resistanceDisease diagnosticsDisease-relevant assaysVariantsClinical case reportBiological mechanismsAssayCase reportClinical reportsSurvival rate
2023
Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Cohen J, Huang S, Koczwara K, Woods K, Ho V, Woodman K, Arbiser J, Daman K, Lek M, Emerson C, DeSimone A. Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism. Cell Death & Disease 2023, 14: 749. PMID: 37973788, PMCID: PMC10654915, DOI: 10.1038/s41419-023-06257-2.Peer-Reviewed Original ResearchConceptsMTOR-independent mechanismsFacioscapulohumeral muscular dystrophyDUX4 transcriptsDUX4 activityMultiple signal transduction pathwaysSignal transduction pathwaysTherapeutic developmentDUX4 proteinDUX4 expressionTransduction pathwaysPolyadenylation sitesChromosome 4DUX4 geneMechanisms of toxicityAutophagy pathwayExpression of ULK1DUX4Cellular autophagyCell deathRelevant pathwaysMuscular dystrophyMolecular methodsPathwaySkeletal muscleTranscriptsP154 The generation of a GNE myopathy patient-derived biobank enables the study of disease-relevant cellular phenotypes across multiple pathogenic variants
Koczwara K, Lake N, Huang S, DeSimone A, Pajusalu S, Branford K, Hallak D, Woodman K, Xu J, Lek A, Best H, Habib A, Avelar J, Martin V, Mozaffar T, Shieh P, Weisleder N, Lek M. P154 The generation of a GNE myopathy patient-derived biobank enables the study of disease-relevant cellular phenotypes across multiple pathogenic variants. Neuromuscular Disorders 2023, 33: s138. DOI: 10.1016/j.nmd.2023.07.286.Peer-Reviewed Original ResearchPathogenic mutationsCRISPR/Cas9 knockoutDisease-relevant cell typesSialic acid biosynthesis pathwayCellular disease modelsMyogenic cell lineCell linesGNE myopathy patientsPatient-derived cell linesGNE activityWhole-genome sequencingGNE proteinPathogenic variantsBiosynthesis pathwayDisease-relevant cellular phenotypesCellular functionsMyogenic lineageCellular phenotypesRNA sequencingBifunctional enzymeGenome sequencingMultiple pathogenic variantsReduced enzymatic activitySkeletal muscle atrophyMyopathy patientsDeath after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne’s Muscular Dystrophy
Lek A, Wong B, Keeler A, Blackwood M, Ma K, Huang S, Sylvia K, Batista A, Artinian R, Kokoski D, Parajuli S, Putra J, Carreon C, Lidov H, Woodman K, Pajusalu S, Spinazzola J, Gallagher T, LaRovere J, Balderson D, Black L, Sutton K, Horgan R, Lek M, Flotte T. Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne’s Muscular Dystrophy. New England Journal Of Medicine 2023, 389: 1203-1210. PMID: 37754285, DOI: 10.1056/nejmoa2307798.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeDuchenne muscular dystrophyMuscular dystrophyAdvanced Duchenne muscular dystrophySevere diffuse alveolar damageDiffuse alveolar damageRespiratory distress syndromeMild cardiac dysfunctionT cell reactivityInnate immune reactionsVirus serotype 9Gene therapyAlveolar damagePericardial effusionDistress syndromeCardiac dysfunctionPostmortem examinationImmune reactionsRAAV gene therapyBody weightPatientsTherapySerotype 9Recombinant adenoDystrophyFunctional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery
Gong Y, Wu Q, Huang S, Fu Z, Ye J, Liu R, Lin S, Guan W, Yang N, Li J, Liang H, Zhou H. Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery. Advanced Biology 2023, 7: e2300007. PMID: 37140139, DOI: 10.1002/adbi.202300007.Peer-Reviewed Original ResearchConceptsMorbid obese patientsMC4R variantsObese patientsWeight lossExcess weight lossCommon genetic causeBariatric surgeryMetabolic surgeryObesity cohortObese populationMonths postsurgeryPatientsSurgery proceduresPersonalized treatmentFunction variantsSurgeryGenetic causeG233V103IR165WCohortLarge size cohortObesityPostsurgeryEWL
2021
Effectiveness of companion-intensive multi-aspect weight management in Chinese adults with obesity: a 6-month multicenter randomized clinical trial
Jiang W, Huang S, Ma S, Gong Y, Fu Z, Zhou L, Hu W, Mao G, Ma Z, Yang L, Tang G, Sun X, Zhang P, Bai J, Chen L, Shi B, Ye X, Zhou H. Effectiveness of companion-intensive multi-aspect weight management in Chinese adults with obesity: a 6-month multicenter randomized clinical trial. Nutrition & Metabolism 2021, 18: 17. PMID: 33536048, PMCID: PMC7856778, DOI: 10.1186/s12986-020-00511-6.Peer-Reviewed Original ResearchNon-alcoholic fatty liver disease (NAFLD) scoreBody mass indexBody fat massVisceral fat areaWeight managementSignificant weight lossTotal cholesterolChinese adultsClinical trialsWeight lossBody compositionVisceral fat area ratioChinese Clinical Trial RegistryMeal replacementMonthly faceLiver Disease scoreClinical Trials RegistryEarly lifestyle interventionsObese Chinese adultsSkeletal muscle massFat area ratioOnline InstructionsHOMA-IRLifestyle interventionHighest tertileExome sequencing in paediatric patients with movement disorders
Kwong AK, Tsang MH, Fung JL, Mak CC, Chan KL, Rodenburg RJT, Lek M, Huang S, Pajusalu S, Yau MM, Tsoi C, Fung S, Liu KT, Ma CK, Wong S, Yau EK, Tai SM, Fung EL, Wu NS, Tsung LY, Smeitink J, Chung BH, Fung CW. Exome sequencing in paediatric patients with movement disorders. Orphanet Journal Of Rare Diseases 2021, 16: 32. PMID: 33446253, PMCID: PMC7809769, DOI: 10.1186/s13023-021-01688-6.Peer-Reviewed Original ResearchConceptsMovement disordersWhole-exome sequencingPediatric patientsPotential treatment implicationsGlobus pallidus interna deep brain stimulationGenetic diagnosisExome sequencingTreatment implicationsDeep brain stimulationEffective clinical managementHeterogeneous neurological diseasesClinical improvementHypokinetic disordersClinical managementDiagnostic yieldHyperkinetic disorderDisease-causing variantsBrain stimulationPatientsNeurological diseasesCohortDisordersDiagnosisGenetic etiologyPrecision medicine
2020
Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy
Lek A, Zhang Y, Woodman KG, Huang S, DeSimone AM, Cohen J, Ho V, Conner J, Mead L, Kodani A, Pakula A, Sanjana N, King OD, Jones PL, Wagner KR, Lek M, Kunkel LM. Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy. Science Translational Medicine 2020, 12 PMID: 32213627, PMCID: PMC7304480, DOI: 10.1126/scitranslmed.aay0271.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPRCellular hypoxia responseFacioscapulohumeral muscular dystrophyHypoxia responseCell deathTherapeutic discoveryGenome-wide perturbationsComplex genetic diseasesEmergence of CRISPRUnbiased genetic screeningSelection assaysGene-editing technologyDUX4 proteinCausal genesDUX4 expressionZebrafish modelEpigenetic changesProtein turnoverMuscular dystrophyCRISPRMyogenic lineDUX4Genetic diseasesGenesMechanistic understanding
2015
Investigation of the 53 Markers in a DNA-Based Prognostic Test Revealing New Predisposition Genes for Adolescent Idiopathic Scoliosis
Xu L, Huang S, Qin X, Mao S, Qiao J, Qian BP, Qiu Y, Zhu Z. Investigation of the 53 Markers in a DNA-Based Prognostic Test Revealing New Predisposition Genes for Adolescent Idiopathic Scoliosis. Spine 2015, 40: 1086-1091. PMID: 25811265, DOI: 10.1097/brs.0000000000000900.Peer-Reviewed Original ResearchConceptsNew predisposition genesSingle nucleotide polymorphismsAssociation studiesGene-based association studyPredisposition genesGenetic association studiesEtiology of AISGenesNucleotide polymorphismsSusceptibility of AISDNA samplesDifferent pathwaysInvader assayDifferences of genotypeAllele APopulation summariesAllele distributionCentral neural systemAllele GMultifactorial diseaseAllele CGenotype frequenciesAllele T