NLM DIR Seminar Schedule
UPCOMING SEMINARS
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Dec. 10, 2024 Amr Elsawy
AI for Age-Related Macular Degeneration on Optical Coherence Tomography -
Dec. 17, 2024 Joey Thole
TBD -
Jan. 7, 2025 Qiao Jin
TBD -
Jan. 14, 2025 Ryan Bell
TBD -
Jan. 21, 2025 Qingqing Zhu
TBD
RECENT SEMINARS
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Dec. 3, 2024 Sarvesh Soni
Toward Relieving Clinician Burden by Automatically Generating Progress Notes -
Nov. 19, 2024 Benjamin Lee
Reiterative Translation in Stop-Free Circular RNAs -
Nov. 12, 2024 Devlina Chakravarty
Fold-switching reveals blind spots in AlphaFold predictions -
Nov. 5, 2024 Max Burroughs
Revisiting the co-evolution of multicellularity and immunity across the tree of life -
Nov. 4, 2024 Finn Werner
African Swine Fever Virus transcription – from transcriptome to molecular structure
Scheduled Seminars on Dec. 4, 2023
Contact NLMDIRSeminarScheduling@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.