BIEN Seminar Series: Dr. Hirosha Geekiyanage, UC Merced

About

MicroRNAs (miRNAs) are small non-coding RNAs, typically 21–22 nucleotides in length, that regulate gene expression by base-pairing with complementary mRNA targets. This regulation is mediated by Argonaute 2 (AGO2), the catalytic component of the miRNA-induced silencing complex (miRISC), leading to translational repression or mRNA degradation. While miRNAs are well established as intracellular gene regulators, extracellular miRNAs are also found in body fluids such as blood and cerebrospinal fluid. To date, extracellular miRNAs have been regarded primarily as biomarkers reflecting the pathophysiology of their cells of origin. Our studies demonstrate that extracellular miRNAs in blood plasma and CSF are predominantly contained within AGO2 complexes and retain the ability to base-pair with complementary RNA targets in a seed-dependent, bona fide miRISC manner. These findings raise a fundamental question: can miRISC exported from donor cells into the extracellular milieu be taken up by recipient cells to regulate their endogenous gene expression? Our research addresses this question by systematically evaluating the structural integrity, uptake mechanisms and regulatory capacity of extracellular miRISC in recipient cells—thereby challenging the prevailing dogma that miRNA function is confined to their cells of origin and establishing a new framework for intercellular RNA signaling. The impact of this work is twofold. First, it will redefine fundamental miRNA biology by overturning the prevailing view that extracellular miRNAs are merely passive byproducts or biomarkers. Instead, it will establish extracellular miRNAs as active mediators of intercellular signaling and gene regulation across cells and tissues, revealing a previously unrecognized mode of cell-cell communication that could transform our understanding of biological function across scale. Second, the findings will lay the foundation for a novel RNA delivery platform. The 2024 Nobel Prize awarded for the discovery of miRNAs underscores the field’s transformative potential and its far-reaching implications for fundamental biology and therapeutic innovation. Biography: Hirosha established her lab as an Assistant Professor at the University of California, Merced in 2023. She earned her PhD in Genetics from Michigan State University and has extensive training in microRNA (miRNA) biology. She completed her postdoctoral research with Dr. Victor Ambros, recipient of the 2024 Nobel Prize for the discovery of miRNAs. Hirosha’s prior work identified miRNAs that regulate amyloid-β levels in the brain, contributing to Alzheimer’s disease, and demonstrated that miRNAs can serve as both therapeutic targets and non-invasive early diagnostic biomarkers for Alzheimer’s disease. In addition, her research identified that infectivity of the oncolytic measles virus can be modulated by miRNAs when used as a therapeutic intervention for glioblastoma, breast, and ovarian cancers. At UC Merced, the Geekiyanage Lab focuses on elucidating the mechanisms governing miRNA export from cells, their delivery to naïve recipient cells, and their regulatory functions—work that aims to establish new therapeutic platforms and strategies. Hirosha teaches Fundamentals of Molecular Biology and Biomolecular Engineering at UC Merced.