Projects
Key areas of current research include the elucidation of RNA biogenesis, RNA processing and modifications, RNA coding of phenotypic variability, and establishing the role of RNA in disease and the exploration of RNA-based-and RNA-targeted therapies.
Research Areas
Listed below are the research projects that our researchers are involved in.
Biochemistry and Biophysics
RNA methyltransferases
We are interested in understanding the molecular basis underlying the protein-RNA interactions involved in a broad range of cellular activities. One of our recent efforts concerns the structure-function of RNA modifying enzymes. Through a structural biology approach, combined with biochemical and cellular assays, we aim to elucidate the molecular mechanisms of these enzymes at atomic resolution. For instance, our structure-function characterization of the ZCCHC4 protein, a 28S rRNA-specific m6A methyltransferase, reveals an autoinhibitory mechanism underpinning the specific recognition between ZCCHC4 and the RNA substrate with a stem-loop structure. Our long-term goal is to elucidate how individual RNA modifying enzymes have evolved into distinct substrate specificity.
Visit Dr. Jikui Song’s profile
Translation, RNA-binding proteins, RNA disease
Controlled protein translation is an integral component of regulated gene expression, and allows cells to respond rapidly to changing conditions. Translation is heavily regulated during its initiation, where a plethora of protein factors coordinate with ribosomal subunits and initiator tRNA to ensure efficient and faithful identification of the mRNA start codon. We aim to decipher the molecular and biophysical mechanisms of this highly intricate, exquisitely dynamic process. We focus on how mRNA–factor interactions guide recognition of the mRNA 5ʹ cap by initiation factor eIF4F, how mRNA is loaded onto the 40S subunit, and how the resulting 48S pre-initiation complex scans the mRNA leader to locate the start codon. We probe these molecular mechanisms with a combination of biochemical and single-molecule biophysics approaches. We aim to understand how the distinct properties of different mRNAs modulate initiation, how disease states reconfigure initiation dynamics, and how therapeutic interventions mitigate dysfunction.
Visit Dr. Sean O’Leary’s Profile
Transcription-Translation Coupling, Structure Of Nascent RNA, Gene Expression
The absence of a nuclear membrane in bacteria allows the RNA to be translated while being transcribed. The occurrence of both processes on the same RNA at the same time results in a dynamic interplay between RNA polymerase and ribosome, coupling transcription and translation. This coupling determines the structure of the nascent RNA between the polymerase and the ribosome. RNA structures can affect transcription and translation. The signal for intrinsic termination of transcription consists of a stem loop followed by six-eight Us. Shifting of the reading frame of translation is promoted by pseudo loops within the mRNA. The effect of RNA structures on transcription and translation is well documented but is less understood when both processes are coupled. To elucidate this interplay, we are bringing to bear single molecule and cryo-EM technology, in collaboration with Seán O’Leary, UCR, and Richard Ebright, Rutgers University, respectively.
Visit Dr. Gregor Blaha’s profile
Circulating RNA, RNA structure, RNA modification
Non-coding RNAs participate in gene expression regulation, and are highly relevant to pathological development. They are stably present in diverse body fluids and can be sampled non-invasively for clinical tests. Thus, circulating RNAs have great potential to be disease biomarkers. To improve discovery of effective RNA markers, one of our research focuses is to detect circulating RNAs, in particular, the RNAs enclosed in extracellular vesicles (EVs). EVs are important cell-cell communicators that can transport RNAs to recipient cells to carry out specific functions. Analyzing EV RNAs could reveal effective circulating RNA markers for disease diagnosis and prognosis. We are also interested in analysis of nucleic acid folding, another factor affecting gene expression. Working with our collaborator, we have developed synthetic receptor arrays for differentiation of diverse DNA folding motifs like G-quadruplex, hairpins, i-motifs, and triplexes. We are working on expanding this method to analyze RNA structures.
Nanopore-based RNA Sensing and Biophysics
The translocation of molecules, particularly protein and RNA, are ubiquitous and vital to cellular life. Furthermore, protein and mRNA undergo a plethora of modifications which diversifies their function and creates sub-populations that are difficult to detect using bulk ensemble measurements. Using a single nanopore as a sensor, RNA molecules can be probed and characterized by size, shape, and charge. Based on the physiochemical shift in molecular properties which is typical of binding events (e.g. complex formation), folding (e.g. secondary structure), and mutations (e.g. stability of secondary structure), a host of single molecule biophysics can be probed and provide unique insight into RNA biology. Our lab focuses on technology/technique development which can push the limits of single molecule sensing and improve on the time resolution of sensing (~microsecond resolution), capture rate (i.e. sensitivity), and specificity of measuring essential biophysical properties of molecules.
Visit Kevin Freedman's Profile
Disease and Medicine
Misregulation and Dysfunction of RNA Processing in Neurological Disorders
Mutations in RNA binding proteins and splice sites can lead to neurodegenerative diseases. Emerging evidence also suggest neurodegenerative diseases exhibit misregulated splicing events. We study how alternative splicing and NMD are mis-regulated in neurodegenerative diseases, and how genetic risk variants in RNA binding proteins and splicing substrates contribute to disease pathogenesis. In keeping with their morphological and functional complexity mammalian brains make the most extensive use of alternative splicing and NMD. Such complexity increases the possibility of gene expression going haywire and consequently brain disease. On the other hand, we envision cell type specific RNA processing events could be harnessed to develop therapies of higher specificity and efficacy.
Visit Dr. Sika Zheng’s profile
RNA viruses; RNAi; viral suppressors of RNAi (VSRs)
My lab investigates the host immune responses to RNA viruses and their counter-defense strategies. Studies from my lab and others have shown that the conserved RNA interference (RNAi) pathway directs a potent antiviral immunity mechanism against RNA viruses in plants, insects, nematodes and mammals. As a result, successful virus infection requires active suppression of antiviral RNAi by viral suppressors of RNAi (VSRs). Currently, we focus on the mechanistic and functional characterization of antiviral RNAi in plants and mammals.
Visit Dr. Shou-Wei Ding’s profile
RNA viruses/Vaccine Development/Drug Discovery
Our research program emphasizes on elucidating the contributions of both viral and host determinants to viral virulence associated with emerging pathogenic RNA viruses, with the ultimate goal to develop novel therapeutic options, antivirals and vaccines, against these viruses. Currently, our working models include influenza, ZIKA and SARS-2 viruses.
Cardiovascular disease, metabolic disorders, small non-coding RNAs
The focus of my laboratory is to investigate the molecular mechanisms of cardiovascular and metabolic diseases. My research program has focused on how chronic inflammation and xenobiotic exposures increase the risk of atherosclerosis and metabolic disorders. Our research has revealed important new functions of several key signaling pathways including xenobiotic receptor PXR and inflammatory mediator IKKβ in the regulation of inflammation, xenobiotic metabolism, atherogenesis, obesity, and insulin resistance. We are currently investigating how newly discovered small non-coding RNAs (e.g., tsRNAs) contribute to the development of cardiometabolic disease.
VISIT DR. CHANGCHENG ZHOU'S PROFILE
Gene Regulation
Small RNAs, RNA modifications
The Chen lab uses Arabidopsis thaliana as a model to study small RNAs, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), which serve as specificity factors in transcriptional and posttranscriptional gene silencing. In the past two decades, research in her lab focused on elucidating the mechanisms underlying small RNA biogenesis, turnover, and modes of action. A current focus is to study how miRNAs and siRNAs serve as mobile signals in plants’ responses to environments and what mechanisms govern the non-cell autonomous activities of small RNAs. A second research direction centers on noncanonical RNA capping by cellular metabolites, such as NAD, FAD, and dpCoA. The goals are to uncover the mechanisms underlying the deposition and removal of the noncanonical caps, elucidate their molecular functions, and to discover the biological processes regulated by noncanonical RNA capping.
VISIT DR. XUEMEI CHEN'S WEBSITE
Epitranscriptomics
The major objective of the research projects in the Wang laboratory related to RNA is to understand the contributions of post-transcriptional modifications of RNA in gene regulation and human diseases. Current research projects include: (1) identification and functional characterizations of cellular proteins that are involved in the recognition, installation and removal (i.e., reader, writer and eraser proteins) of modified nucleosides in RNA; (2) targeted quantifications of modified ribonucleosides and epitranscriptomic reader, writer, and eraser proteins in cells and tissues; (3) elucidation of the molecular mechanisms through which RNA modifications contribute to human diseases, especially cancer and neurodegenerative disorders, and resistance to chemo- and radiation therapy. Highly interdisciplinary approaches, including mass spectrometry-based bioanalytical chemistry, proteomics, next-generation sequencing, molecular biology and cell biology, are employed in these projects.
Visit Dr. Yinsheng Wang’s profile
Alternative Splicing, Nonsense-mediated mRNA Decay (NMD)
Our lab is interested in how alternative splicing and NMD are regulated in a cell type specific manner to shape cell type specific gene expression, and their contributions to cell fate determination and maturation. Our projects include: (1) how do neurons choose cell type specific exons? (2) to what extent and how do these signature exons contribute to the neuronal phenotypes, neuronal subtype diversity, and the establishment of neural circuits? (3) mechanism of NMD targeting natural transcripts and NMD’s biological roles in cellular functions. We integrate approaches of biochemistry, molecular and cellular neuroscience, imaging, mouse genetics, functional genomics, and computational biology to tackle these fundamental questions.
Visit Dr. Sika Zheng’s profile
Chromatin structure/epigenetics and the role of long non coding RNA
Dr. Karine Le Roch, PhD is a Professor of Molecular, Cell and Systems Biology. She has over 20 years of broad expertise in drug discovery and functional genomics in eukaryotic organisms with a particular interest in apicomplexan parasites including Plasmodium falciparum, the protozoan parasite that causes the deadliest form of malaria in humans. At UCR Prof. Le Roch has developed high-throughput methodologies to identify key molecular pathways underlying pathogen and host cell development with a particular interest in epigenetics and chromatin structure. More recently, she has developed new approaches to understand the role of Long Non-Coding RNAs (lncRNAs) in Apicomplexan parasites. lncRNAs are emerging as new players in many aspects of biological processes including transcriptional and post-transcriptional regulation of gene expression. Prof Le Roch seeks to better understand not only the function of lncRNAs in apicomplexan parasites but their potential as new lncRNA-based therapies.
Visit Dr. Karine Le Roch’s profile
Non-coding RNAs, Arabidopsis, Light Signaling
Plant growth and development are profoundly regulated by environmental light cues. The wavelength, intensity, and periodicity of the ambient light environment are continuously monitored by plants via photoreceptors to modulate the expression of light-responsive genes, thereby generating adaptive responses. Our lab is interested in elucidating functions of non-coding RNAs in the light control of plant growth and photosynthesis.
tsRNAs, rsRNAs, RNA modifications
We explore the expanding universe of small RNAs (e.g., tsRNAs, rsRNAs) with new experimental and analytical tools, decoding the 'RNA code' (RNA expression & modification profiles) in regard to gene regulation in embryonic cell fate control and sperm-mediated epigenetic inheritance, and to discover their diseases associations such as with metabolic disorders and cancer.
RNA-binding proteins, microRNAs, post-transcriptional gene regulation
Gene expression is elaborately controlled at the post-transcriptional level through interactions of small RNAs (microRNAs) and RNA-binding proteins (RBPs) with specific sites on messenger RNAs, affecting the stability and translation rates of the mRNAs, and altering the protein output. Binding of microRNAs or RBPs at nearby sites on the same mRNA allows for additive or synergistic interactions between the regulators themselves, imparting a higher order of combinatorial control. We focus on the overall mapping and principles of the interactions between mRNAs and their controlling factors - microRNAs and RBPs, and the interplay between these factors, employing a mixture of tools in molecular biology, bioinformatics and cell biology, with applications in neurobiology.
Visit Dr. Ted Karginov’s profile
Fungal Biology; Transposable elements; Genome Defense; Gene expression profiling
Research in the group studies fungi, their biology, and interactions with plant and animal hosts. We use genome and transcriptome profiling to examine microbe-host interactions, genome size evolution, and genome defenses impacting transposable elements.
Visit Dr. Jason Stajich's Profile
RNA Informatics
Alternative Splicing, Isoform, Algorithm
We are interested in computational analyses and methods concerning all aspects of alternative splicing such as transcriptome assembly and abundance quantification, the inference of isoform functions, subcellular localization and interactions, the usages of splice sites, the impact of mutations on splicing, etc.
Genome Biology and Chemical Genomics
The Girke lab focuses on fundamental research questions at the intersection of genome biology and chemical genomics. These include: Which factors in genomes, transcriptomes, proteomes and metabolomes are functionally relevant and perturbable by small molecules? What properties of small molecules and their targets are the main drivers for compound-target interactions? How can these insights be used to develop precision perturbation strategies for biological processes with translational applications in both agriculture and human health? To address these questions, the group develops computational methods for analyzing both large-scale omics and small molecule bioactivity data. This includes discovery-oriented projects, as well as algorithm and software development projects for data types from a variety of Big Data technologies, such as NGS, genome-wide profiling approaches and chemical genomics. As part of the multidisciplinary nature of my field, the group frequently collaborates with experimental scientists on data analysis projects of complex biological problems.
Visit Dr. Thomas Girke’s profile
Transcription Control, Epigenetics, Chromatin
The Lonardi lab is primarily interested in the analysis of sequencing data for a variety of molecular biology applications, e.g., de novo genome assembly, epigenetics, gene expression, 3D genome structure, genome editing, among others. In the RNA domain, the group has studied small RNAs in plants (doi:10.1186/1471-2199-9-6 and doi:10.1093/mp/sst051), gene expression in metastatic melanoma (doi:10.1073/pnas.0905139106), cancer type classification (doi:10.1007/978-3-030-00834-5_7), transcription control in the human malaria parasite (doi:10.1101/gr.101063.109 and doi:10.1186/1471-2164-15-347), discovery of transcription factor binding sites (doi:10.1186/1471-2164-12-601), chromatin structure from Hi-C data (doi:10.1093/bioinformatics/btz362, doi:10.1186/s13059-020-02167-0), detection of essential genes (doi:10.1186/s12859-020-03688-y), and genome editing (doi:10.1038/s41467-022-28540-0, doi:10.1016/j.ymben.2019.06.007)
Visit Dr. Stefano Lonardi’s profile
Statistical Genomics
The Vivian Li Lab is interested in statistical/computational modeling and algorithm development, as well as their applications to bulk-tissue and single-cell high-throughput sequencing data. Major research topics of our lab include (1) developing statistical and machine learning models to denoise, deconvolve, and compare genomics data, and (2) using statistical and computational models to advance knowledge in the regulation of gene expression and RNA processing.
Mathematical and Computational Biology
The Heyrim Cho lab is interested in developing mathematical models that describe the cell state dynamics of transcriptomics and computational methods that allow to efficiently simulate the models. The group has developed phenotype structured cell state models of hematopoiesis and acute myeloid leukemia progression using single-cell RNA sequencing data, and compared/contrasted continuum cell state models in distinct cell state geometries including graph and multi-dimensional space derived from single-cell sequencing data.
VISIT DR. HEYRIM CHO'S PROFILE
Exploring Biophysics Through Computations
The Palermo lab masters molecular dynamics and multiscale modeling, quantum mechanical methods and cryo-electron microscopy (cryo-EM) processing techniques. Through these methods, we perform large-scale simulations of proteins and nucleic acids, with interest in bimolecular allostery, conformational change, and catalysis.