Improved Diagnosis and Treatment of Cushing's Disease

改进库欣病的诊断和治疗

• 批准号: 10915993
• 负责人: Prashant Chittiboina
• 金额: $ 149.95万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10915993
• 关键词: Anterior Pituitary Gland; Benign; Cell Cycle; Cell physiology; Clinical; Controlled Environment; Corticotropin; DNA Sequence Alteration; Detection; Diagnosis; Disease; Disease model; Epigenetic Process; Excision; Functional disorder; Gene Expression Profiling; Genes; Genetic; Genetic Transcription; Genomics; Goals; Hormone secretion; Human; Image; In Vitro; Lead; Light; Longevity; Magnetic Resonance Imaging; Medical; Metabolic; Methylation; Modeling; Molecular; Morbidity - disease rate; Mutation; Operative Surgical Procedures; PMAIP1 gene; Pathway interactions; Patient-Focused Outcomes; Patients; Physiology; Pituitary Gland; Pituitary Gland Adenoma; Pituitary Neoplasms; Pituitary-dependent Cushing' s disease; Research; Somatic Mutation; Technology; Treatment Failure; USP8 gene; adenoma; comparative; effective therapy; epigenomics; improved; improved outcome; induced pluripotent stem cell; metabolic imaging; new therapeutic target; novel; personalized medicine; preservation; stem cell model; treatment choice; treatment strategy; tumor; tumorigenesis

The overarching goal of the Chittiboina lab is to unravel the mechanisms underlying the formation and progression of pituitary adenomas with a view to identifying novel therapeutic targets and enhancing patient outcomes. The research is geared towards achieving a comprehensive understanding of the molecular and cellular processes in pituitary adenomas and formulating personalized treatment strategies using omics-based approaches, benchtop models, and clinical pipelines. One of the research's specific aims is to identify common pathways in Cushings disease (CD) adenomas. These adenomas are an ideal disease model to understand pituitary pathophysiology. Chittiboina lab has found evidence of common transcriptional dysregulation, genomic methylation changes, and metabolic reprogramming in CD adenomas, independent of somatic mutations. The hypothesis is that CD adenomas share targetable common downstream pathways, irrespective of genomic mutations. To study the mechanisms underlying adenoma formation, the lab is employing iPSC (induced pluripotent stem cell) derived models. These models help mimic the disease state in a controlled environment, allowing for the study of known genetic mutation (USP8) and newly discovered epigenomic changes (PMAIP1, PPP1R17 genes) on the cell-cycle and hormone secretion pathways. Additionally, the research involves the in-vitro replication of USP8 mutations. The use of iPSC models not only aids in understanding adenoma mechanisms but also paves the way for studying normal pituitary physiology. This research approach holds great promise for shedding light on the complexities of pituitary adenomas and eventually developing more effective treatments.

Chittiboina实验室的首要目标是揭示垂体腺瘤形成和发展的机制，以确定新的治疗靶点并提高患者的治疗效果。该研究旨在全面了解垂体腺瘤的分子和细胞过程，并利用基于组学的方法、台式模型和临床管道制定个性化治疗策略。

项目成果

Canonical and Non-Canonical Roles of PFKFB3 in Brain Tumors.

• DOI: 10.3390/cells10112913
• 发表时间: 2021-10-27
• 期刊: Cells
• 影响因子: 6
• 作者: Alvarez R;Mandal D;Chittiboina P
• 通讯作者: Chittiboina P

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

• DOI: 10.1038/pr.2017.58
• 发表时间: 2017-08
• 期刊: Pediatric research
• 影响因子: 3.6
• 作者: Gkourogianni A;Sinaii N;Jackson SH;Karageorgiadis AS;Lyssikatos C;Belyavskaya E;Keil MF;Zilbermint M;Chittiboina P;Stratakis CA;Lodish MB
• 通讯作者: Lodish MB

Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

• DOI: 10.1016/j.jecr.2017.02.001
• 发表时间: 2017-06-01
• 期刊: Journal of clinical and translational endocrinology case reports
• 作者: Kasturi, Kannan;Fernandes, Lucas;Lodish, Maya
• 通讯作者: Lodish, Maya

Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1.

• DOI: 10.1016/j.mce.2017.10.003
• 发表时间: 2018-07-15
• 期刊: Molecular and cellular endocrinology
• 影响因子: 4.1
• 作者: Lu J;Montgomery BK;Chatain GP;Bugarini A;Zhang Q;Wang X;Edwards NA;Ray-Chaudhury A;Merrill MJ;Lonser RR;Chittiboina P
• 通讯作者: Chittiboina P

Optical Imaging Technology: A Useful Tool to Identify Remission in Cushing Disease After Surgery.

光学成像技术：识别手术后库欣病缓解情况的有用工具。

• DOI: 10.1055/a-0801-8917
• 发表时间: 2019
• 期刊: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
• 作者: Afshari,Ali;Keil,Margaret;Lyssikatos,Charalampos;Belyavskaya,Elena;Valdés,Nuria;Chowdhry,FatimaA;Parsa,Kian;Ardeshirpour,Yasaman;Pursley,Randall;Khare,Siddharth;Kainerstorfer,JanaM;Chittiboina,Prashant;Lodish,MayaB;Mazzuchi,T
• 通讯作者: Mazzuchi,T