The UCI recipients of the NIH Director’s New Innovator Awards, which support cutting-edge research in biology and biomedical engineering, are (from left) Fangyuan Ding, assistant professor of biomedical engineering; Evgeny Kvon, assistant professor of developmental and cell biology; and Xiaoyu Shi, assistant professor of developmental and cell biology. UCI

Irvine, Calif., Oct. 6, 2022 – Three University of California, Irvine scientists have been selected by the National Institutes of Health to receive NIH Director’s New Innovator Awards, bringing a total of $7 million to UCI for research projects in biology and biomedical engineering.

Fangyuan Ding, assistant professor of biomedical engineering, and Evgeny Kvon and Xiaoyu Shi, both assistant professors of developmental and cell biology, are among 72 researchers chosen by the NIH under its High-Risk, High-Reward Research program. New Innovator Awards are bestowed on early-to-midcareer scientists who propose “visionary and broadly impactful meritorious behavioral and biomedical engineering projects,” according to an NIH press release.

The NIH Common Fund has granted $2.3 million for a five-year project headed by Ding, the goal of which is to pursue the next jump in resolution in RNA mapping. Current tools can be used to characterize only long-sequence RNA molecules, while other research pursuits – such as splicing isoforms, working with miRNA and RNA editing – involve much shorter segments. Ding’s group is in the process of creating a new tool named Smoothy-Fish that enables the spatial mapping of all types of RNA molecules in individual cells.

“This project will contribute to the field in two ways. Technically, we will develop a low-cost, universally applicable RNA mapping tool with single-base resolution; and scientifically, we will create a comprehensive map of RNA regulation, including previously inaccessible species,” Ding said. “Smoothy-Fish will help us open a new era of RNA biology and move us from basic science research to clinical applications.”

In a five-year project supported by about $2.4 million in NIH funding, Kvon and his research group will unravel the mysteries of how regulatory DNA switches called “enhancers” regulate their target genes from remote distances, across many thousands or even millions of DNA bases. Remote enhancers determine when and where in the body different genes turn on and off, and according to Kvon, there is mounting evidence linking them to human disease. Traditional methods of studying this process have been hampered by technical limitations, but Kvon will employ new genome editing technologies in mice to characterize remote enhancers and identify genetic factors critical to this long-range activity.

“Mutations leading to birth defects, heart disease, autism, cancer and other human disorders frequently affect distant-acting transcriptional enhancers, noncoding DNA elements that regulate gene expression,” Kvon said. “We aim to determine how these processes occur over long genomic distances using novel genome editing, genomics and imaging technologies, advancing an essential foundation to understand the pathological consequences of single-nucleotide and structural variations in noncoding regions of the human genome.”

In a five-year project supported by $2.3 million in NIH funding, Shi will investigate the organization of cells in the human body in 3D space, with the knowledge that a cell’s function and fate are determined by its biomolecular composition and position in its 3D environment. Analysis of isolated cells currently causes an unavoidable loss of spatial information. The goal of Shi’s project is to develop GO3D, a “multiomics” technology featuring gel-based optical isolation, which will enable the profiling of proteins, RNA and DNA of whole tissues with subcellular resolution.

“Three-dimensional organization of cells is intimately linked to human health and disease,” Shi said. “Applications of our GO3D spatial multiomics technology will transform our understanding of many critical biomedical processes, such as Alzheimer’s disease progression, neuron interactions, the tumor microenvironment, wound healing and the microbiome-host relationship.”

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