Hannah M. Seagle

Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction We prioritized 57 druggable targets from 212 putative causal genes of metabolic-dysfunction-associated steatotic liver disease (MASLD). Using a drug-repurposing analysis that integrated protein struct...

I am excited to share that our paper has been officially published at AJHG!

www.cell.com/ajhg/fulltex...

07.08.2025 15:44 — 👍 1    🔁 1    💬 0    📌 0

Many thanks to our wonderful co-authors, many of whom are members of the MVP Cardiometabolic Working Group. 7/n @marijana.bsky.social

19.03.2025 18:32 — 👍 1    🔁 0    💬 0    📌 0

Overall, we used a multi-modal approach which demonstrated that contextualizing genetic signals through causal inference methods and protein folding experiments can elucidate potential drug repurposing targets and novel therapeutic discoveries for MASLD. 6/n

19.03.2025 18:31 — 👍 1    🔁 0    💬 1    📌 0

Structural analysis involved creating, to our knowledge, the first computational model of IPE bound to FADS1. We also generated molecular dynamic simulations which showed IPE remains in the binding pocket for >300 ns. These models suggest stable binding modes of IPE to FADS1. 5/n

19.03.2025 18:30 — 👍 0    🔁 0    💬 1    📌 0

Next, we used two-sample Mendelian randomization to proxy the therapeutic effects of these medications on MASLD risk. We found that icosapent ethyl (IPE), proxied by FADS1/FADS2 expression, and fingolimod, proxied by S1PR2 expression, have protective effects against MASLD.

19.03.2025 18:28 — 👍 0    🔁 0    💬 1    📌 0

We performed TWAS with previously published MVP sumstats, providing us with genetically predicted gene expression associated with MASLD risk. These genes were mapped to drug targets, refined by direction of effect & drug mechanism, and taken forward for casual analysis. 3/n

19.03.2025 18:28 — 👍 0    🔁 0    💬 1    📌 0

Millions of Americans have MASLD, but there are currently a limited number of treatment options. We developed a genome-informed drug repurposing approach, which integrates genetic, molecular, and pharmacological data, to identify new treatments for MASLD. 2/n

19.03.2025 18:28 — 👍 0    🔁 0    💬 1    📌 0

Genomics-Informed Drug Repurposing Strategy Identifies Novel Therapeutic Targets for Metabolic Dysfunction-Associated Steatotic Liver Disease Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving treatment of diseases. We employed a cross-disciplinar...

I am excited to share our new preprint “Genomics-Informed Drug Repurposing Strategy Identifies Novel Therapeutic Targets for Metabolic Dysfunction-Associated Steatotic Liver Disease.” www.medrxiv.org/content/10.1.... 1/n

19.03.2025 18:27 — 👍 3    🔁 2    💬 1    📌 0

Excited to share our work on drug repurposing for metabolic dysfunction-associated steatotic liver disease this week at the Keystone Symposia meeting. I am also so honored and grateful to receive a scholarship award!

24.02.2025 15:28 — 👍 2    🔁 0    💬 0    📌 0