Yasuda Lab
Principal Investigator: Makiko Yasuda
Institution: Icahn School of Medicine at Mount Sinai (New York, NY)
Primary Subfield: Genetics/Genomics
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Project Summary Synthetic small interfering RNAs (siRNAs), which are related to endogenous microRNAs (miRNAs), have recently emerged as a transformative class of drugs in the liver. However, it remains a hurdle to achieve efficient gene silencing in certain extrahepatic tissues. Recent studies from the Lai lab identified an unexpected role for 5-aminolevulinic acid synthase 1 (ALAS1), the first enzyme in heme biosynthesis, to repress miRNA accumulation by limiting formation of the RNA-induced silencing complex (RISC). As siRNAs also exert gene silencing through the RISC machinery, these data raise the intriguing possibility that suppression of ALAS1 may enhance siRNA activity, and therefore, might be harnessed as a general adjuvant for therapeutic RNA interference (RNAi). Preliminary data produced in collaboration with the Yasuda lab support this notion. Notably, ALAS1 is the target of an FDA-approved RNAi therapeutic, givosiran. That this drug is well-tolerated by patients and that mice lacking discernable hepatocyte ALAS activity are healthy support the safety of ALAS1 suppression in liver. Accordingly, we propose three Aims to establish ALAS1 suppression as a broadly applicable…
Active NIH Awards
- 1R01DK144772-01A1: Mechanism and application of a novel genetic strategy to enhance therapeutic RNAi (2026)
- 5R01DK134783-04: Mechanisms of Intercellular Heme Homeostasis in Liver (2026)
- 5R01DK134783-03: Mechanisms of Intercellular Heme Homeostasis in Liver (2025)
- 5R01DK134783-02: Mechanisms of Intercellular Heme Homeostasis in Liver (2024)
Explore 700+ US Biology Labs on FindBioLabs.com