NLM IRP Seminar Schedule
UPCOMING SEMINARS
RECENT SEMINARS
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July 23, 2024 Yu group
Yu Group Research Update -
July 18, 2024 Xiaofang Jiang
Jiang Lab research updates -
May 30, 2024 Deepak Gupta
Towards Answering Health-related Questions from Medical Videos: Datasets and Approaches -
May 28, 2024 Harutyun Saakyan
Simulation of protein fold evolution with atomistic details -
May 23, 2024 Leslie Ronish
Identification of fold-switching proteins by FLIM-FRET
Scheduled Seminars on Dec. 4, 2023
Contact NLM_IRP_Seminar_Scheduling@mail.nih.gov with questions about this seminar.
Abstract:
The complexity of Alzheimer’s Disease (AD) means that approaches for effective therapeutic target identification and drug development need to be multifaceted. Genetically identified target genes have yet to be shown as clinically effective as drug targets. Data driven approaches to discovery are far more successful when tightly linked to predictive assessment in biological systems. Using a comparative systems approach, we have focused upon the activity of individual pathways to map dysregulated function across human and model systems. Integrated Pathway Activity Analysis (IPAA) compares human brains with 3D Alzheimer’s disease (AD) neural cell culture models, ensuring selection of the most accurate model. This approach identifies crucial pathways and new drug candidates, validated in neural cell culture models, accelerating the development of AD interventions. Precise alignment of cellular model functional recapitulation with human AD pathology streamlines drug discovery and minimizes the risk of clinical trial failures. The P38 MAPK pathway is identified as a key dysregulated pathway, consistently activated in both AD brains and 3D AD neural cell culture models. We validated the impact of this pathway by therapeutic intervention with known clinical p38 MAPK inhibitors. We are now exploring the potential modulation of pathogenic pathways using microRNAs (miRNAs). Utilizing a miRNA-Pathway prediction framework, PanomiR, we systematically analyze the role of miRNAs in regulating the multi-pathway activity events we have discovered related to AD. This approach has led to the identification of key miRNAs that target coordinated groups of disease pathways, offering novel insights into the regulatory mechanisms in AD and highlighting potential therapeutic candidates.