Investigating Disease Activity, Bone Damage and Interleukin-1 Genes in Adult SAPHO Syndrome and Chronic Nonbacterial Osteomyelitis
研究成人 SAPHO 综合征和慢性非细菌性骨髓炎的疾病活动、骨损伤和白细胞介素 1 基因
基本信息
- 批准号:10722534
- 负责人:
- 金额:$ 16.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcneAddressAdultAgreementAreaBindingBioinformaticsChildhoodChronicClinicClinicalClinical InvestigatorClinical ResearchClinical SciencesClinical TrialsCodeDataDevelopmentDiagnosisDiseaseEarly DiagnosisEarly InterventionEffectivenessEnvironmentEtiologyFDA approvedFutureGenesGeneticGenotypeGoalsHyperostosisIL1B geneImageImmunosuppressionInflammationInflammatoryInfrastructureInterleukin-1IowaJointsKnowledgeLarge-Scale SequencingLesionMagnetic Resonance ImagingMeasurementMeasuresMentored Patient-Oriented Research Career Development AwardMentorsMentorshipModelingMulticenter StudiesMutationObservational StudyOsteitisOsteomyelitisOutcomePainPathogenicityPathway interactionsPatient Outcomes AssessmentsPatient-Focused OutcomesPatientsPerformancePharmaceutical PreparationsPositioning AttributePredictive ValueProductivityProspective StudiesPsychometricsRNA SplicingReference StandardsReportingResearchResearch DesignResearch MethodologyResearch PersonnelRheumatismRiskRisk FactorsRoleScienceSignaling ProteinSiteSpecificitySpinal DiseasesStatistical Data InterpretationSterilitySymptomsSyndromeSynovitisSystemic SclerodermaTechniquesTestingTrainingTranslational ResearchUniversitiesVariantVisitWorkautoinflammatory diseasesbonecareercareer developmentchronic painclinical phenotypecohortdesigndisabilitydisease phenotypeexperiencefollow-upgenetic variantgenome sequencingimaging modalityimprovedinhibitorlongitudinal coursemodifiable risknovelnovel markerobservational cohort studypatient orientedprospectiverecruitskillsstemtargeted treatmenttooltreatment guidelinestreatment responsetreatment strategyvariant detectionwhole genome
项目摘要
Project Summary
SAPHO syndrome and chronic nonbacterial osteomyelitis (SAPHO-CNO) is a painful and disabling
autoinflammatory disease primarily targeting bones and joints, with no FDA-approved therapies. Severe sterile
inflammation of multiple bones (osteitis), driven by the interleukin-1 (IL-1) pathway, leads to irreversible bone
damage, chronic pain and disability in adult patients. Critical knowledge gaps remain about disease activity
assessments, risk factors for severe outcomes, and influence of variants in IL-1 pathway genes on clinical
phenotypes in adults. This K23 proposal will propel our understanding of the longitudinal course of SAPHO-
CNO in adults, garnering generalizable knowledge about this understudied and disabling autoinflammatory
disease. The proposed project will investigate clinician, patient and MRI-assessed disease activity in a large
SAPHO-CNO cohort (Aim 1), identify risk factors for bone damage in SAPHO-CNO patients (Aim 2), and
discover IL-1 signaling pathway gene variants and explore their correlation with clinical phenotypes in adults
with SAPHO-CNO (Aim 3). The science resulting from this K23 award will lay the groundwork for a future R01
application. Dr. Aleksander Lenert is spearheading a unique prospective observational study in adult SAPHO-
CNO (the SCS study) designed to address these knowledge gaps. His long-term career goal is to develop into
an independent clinical investigator focused on patient-oriented clinical and translational research in adults with
SAPHO-CNO. Under direct mentorship from Dr. Polly Ferguson (world-leading expert in CNO) and his
experienced mentoring team, Dr. Lenert will build on his foundational research skills to gain critical training and
hands-on experience in agreement and psychometric analyses, latent trajectory modeling, genetic sequencing
analysis and interpretation, and prospective observational cohort study management. In addition to Dr.
Ferguson, his mentoring team includes Dr. Robyn T. Domsic (clinical investigator and observational cohort
study guru in systemic sclerosis), Dr. Daniel H. Solomon (leader in clinical science research in rheumatic
diseases), Dr. Mary Vaughan-Sarrazin (experienced clinical outcomes researcher), and Dr. Jonathan Templin
(measurement science and applied psychometrics researcher). To further guide this scientific proposal,
develop focused training and aid his career development, Dr. Lenert has garnered the support of content area
experts in advanced imaging (Dr. T. Shawn Sato), and genetics and bioinformatics (Drs. Hatem El-Shanti and
Benjamin Darbro). This proposal benefits from an exceptional scientific environment and established
infrastructure at the University of Iowa, including Dr. Polly Ferguson’s world-renown center for the
management of patients with SAPHO-CNO, and for clinical and translational research. Accomplishment of the
proposed Aims for this K23 award will directly benefit adults with SAPHO-CNO, and lead to improved patient
outcomes. The K23 award will provide a framework for Dr. Lenert to acquire advanced methodologic research
skills and experiences necessary to become an independent clinical researcher in adult SAPHO-CNO.
项目摘要
SAPHO综合征和慢性非细菌性骨髓炎(SAPHO-CNO)是一种疼痛和致残性疾病,
严重的自身炎症性疾病主要针对骨骼和关节,没有FDA批准的治疗方法。
由白细胞介素-β 1(IL-β 1)途径驱动的多个骨骼的炎症(骨炎),导致不可逆的骨
在成人患者中的损伤、慢性疼痛和残疾。
评估,严重结局的风险因素,以及IL-10 1通路基因变异对临床
K23的提出将促进我们对SAPHO-1的纵向过程的理解。
CNO在成人中,获得关于这种未充分研究和禁用自身炎症的可推广的知识
拟议的项目将调查临床医生,患者和MRI-MRI评估的疾病活动在一个大的
SAPHO-CNO队列(目标1),确定SAPHO-CNO患者骨损伤的风险因素(目标2),以及
发现IL-12 1信号通路基因变异并探索其与成人临床表型的相关性
与SAPHO-SAPHO CNO合作(目标3)。K23奖的科学成果将为未来的R 01奠定基础
Aleksander Lenert博士正在领导一项独特的前瞻性观察性研究,
CNO(SCS研究)旨在解决这些知识差距。他的长期职业目标是发展成为
一位独立的临床研究者,专注于成人患者的临床和转化研究,
在Polly Ferguson博士(世界领先的CNO专家)及其
经验丰富的指导团队,博士Lenert将建立在他的基础研究技能,以获得关键的培训,
在一致性和心理测量分析、潜在轨迹建模、基因测序方面的实践经验
分析和解释,以及前瞻性观察性队列研究管理。
Ferguson的指导团队包括Robyn T. Domsic博士(临床研究者和观察队列
系统性硬化症研究专家),丹尼尔H.所罗门博士(风湿性关节炎临床科学研究领导者
疾病)、玛丽沃恩-萨拉钦博士(经验丰富的临床结局研究员)和乔纳森坦普林博士
(测量科学和应用心理测量学研究者)。为了进一步指导这一科学建议,
发展有针对性的培训,并帮助他的职业发展,Lenert博士已经获得了内容领域的支持,
高级成像专家(T. Shawn Sato博士)、遗传学和生物信息学专家(Hatem El-Shanti博士和
本杰明Darbro)。这项建议受益于一个特殊的科学环境和建立
爱荷华州大学的基础设施,包括波莉·弗格森博士的世界著名的
SAPHO-CNO患者的管理,以及临床和转化研究。
该K23奖项的拟议目标将直接使患有SAPHO-CNO的成年人受益,并改善患者
K23奖将为Lenert博士提供一个框架,以获得先进的方法学研究
成为成人SAPHO-CNO独立临床研究者所需的技能和经验。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Aleksander Lenert其他文献
Aleksander Lenert的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Research Grant