Improved Diagnosis and Treatment of Cushing's Disease

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

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.