Wu LAB

Dr. Tongbin Wu is dedicated to the study of left ventricular noncompaction (LVNC) and dilated cardiomyopathy (DCM). Using genetics, next-generation sequencing tools and molecular biology, his work aims to understand LVNC and DCM during embryonic development to prevent congenital heart disease and to improve the treatment and diagnosis of patients worldwide. Dr. Wu’s goal is to gain a deeper understanding of these networks, paving the way for the identification of novel therapeutic targets and the development of more effective treatments not only for LVNC but also for other heart diseases.

News From The Wu Lab

Tongbin Wu, Ph.D., has been recruited to Utica and named associate professor of biomedical research and translational medicine at MMRI. In this role, Wu will oversee a laboratory dedicated to heart development and cardiovascular medicine.

Areas of Investigation

Transcriptional regulation in heart development and disease: According to the "Central Dogma”, genetic information flows from DNA to RNA, and then from RNA to protein. As the initial step, transcription is the process of copying a segment of DNA, known as “gene”, into RNA. Transcription regulation determines when and where genes are expressed, influencing the production of proteins, which are indispensable for nearly all biological processes in our body. Transcription regulation profoundly affects the development and function of our body. In the Wu laboratory, we focus on studying transcription factors – proteins regulate transcription – whose malfunction often leads to LVNC and other heart diseases. Understanding the molecular mechanisms by which these transcription factors regulate gene expression during heart development, and how their dysfunction leads to disease, will contribute to the development of innovative therapies in the future.

Post-transcriptional regulation in heart development and disease: Following transcription from DNA, the initial RNA form is known as precursor messenger RNA (pre-mRNA). Pre-mRNA undergoes various post-transcriptional processing or modifications to mature into messenger RNA (mRNA), which serves as the template for protein synthesis. Often mediated by RNA-binding proteins (RBPs), post-transcriptional regulation significantly influences the composition and function of proteins, making it pivotal for the development and function of our body. Built on Dr. Wu’s expertise in RNA biology and cardiovascular medicine, the other major focus of our group is post-transcription regulation by RBPs that are mutated or dysregulated in heart diseases. Utilizing a range of genetic and genomic research tools, our aim is to decipher the intricate gene regulation network within the heart. By doing so, we can identify potential drug targets and devise innovative therapeutic approaches.

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Lab Focus

Genetics

The Wu lab employs models to study heart diseases. Using CRISPR-Cas9 technology, genetic mutations or deletions identified in humans are introduced into the genome, allowing for the observation of disease phenotypes. These models serve as valuable tools for elucidating the molecular mechanisms underlying heart diseases and for conducting pre-clinical testing of potential therapeutic interventions.

Genomics

The Wu lab employs multi-omics genomic approaches to unravel the gene regulation network within the heart. Specifically, bulk or single-cell RNA sequencing (RNA-seq) and spatial gene expression technology are utilized to analyze spatiotemporal gene expression changes during development or under diseased conditions (transcriptomics). Mass spectrometry is employed to investigate protein expression alterations (proteomics) and map out protein interaction networks (interactome). Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is used to pinpoint the binding locations of transcription factors on the genome (epigenomics), while crosslinking and immunoprecipitation followed by sequencing (CLIP-seq) is applied to determine the locations where RNA binding proteins occupy on the RNA (transcriptomics). The integration of information obtained from these techniques provides insights into how gene expression is regulated transcriptionally and post-transcriptionally in the heart at the molecular level.

Molecular & Cell biology

Our lab performs routine molecular and cell biology techniques as the basis for all our research, including polymerase chain reaction (PCR), gel electrophoresis, western blot, immunofluorescence, primary cell cultures, cell line cultures, and more.

Meet Dr. Tongbin Wu

Assistant Professor of Biomedical Research and Translational Medicine

Wu completed his Ph.D. in biochemistry and molecular biology at Wuhan University, Wuhan, China, and his postdoctoral training in molecular cardiology at the University of California San Diego (UCSD), San Diego, California. While at UCSD, Wu’s work was published in highly regarded scientific journals including, Circulation, PNAS, Circulation Research, PLOS Genetics and Nature Structure and Molecular Biology.

Lab Members

Enxu Li, Ph.D.

Postdoctoral Fellow

Li holds a Ph.D. in nutrition and metabolism from the University of Tokyo, Bunkyo, Japan. Li joined MMRI in 2024 with a focus on post-transcriptional regulation of heart development and diseases focusing on Cardiovascular Physiology.

Elise Stanley

Research Assistant

Stanley holds a bachelor's degree in chemistry from Johns Hopkins University, Baltimore, Maryland. Stanley joined MMRI in 2024 with a focus on RBPMS, a vital RNA-binding protein within cardiomyocytes, and Pdlim5, whose alternative splicing/protein isoform expression is regulated by RBPMS.

2024 Summer Fellows

Zhijie Han
Reaghan Sassower

Past Members

Zizhen Liu, 2023-2024

Key Publications

PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle.

Wu, T, Liang, Z, Zhang, Z, Liu, C, Zhang, L, Gu, Y et al.. Circulation. 2022;145 (8):586-602. doi: 10.1161/CIRCULATIONAHA.121.056666. PubMed PMID:34915728 PubMed Central PMC8860879.

Mutations in the PRDM16 gene cause left ventricular noncompaction cardiomyopathy (LVNC) in patients. Using mouse genetics, genomics, and molecular biology tools, Dr. Wu discovered that the loss-of-function of PRDM16 causes “identity crisis” in cardiac cells during heart development, which could be a universal mechanism underlying the etiology of LVNC.

Filamin C is essential for mammalian myocardial integrity

Wu, T, Xu, Y, Zhang, L, Liang, Z, Zhou, X, Evans, SM et al.. PLoS Genet. 2023;19 (1):e1010630. doi: 10.1371/journal.pgen.1010630. PubMed PMID:36706168 PubMed Central PMC9907827.

HSPB7 is indispensable for heart development by modulating actin filament assembly.

Wu, T, Mu, Y, Bogomolovas, J, Fang, X, Veevers, J, Nowak, RB et al.. Proc Natl Acad Sci U S A. 2017;114 (45):11956-11961. doi: 10.1073/pnas.1713763114. Pub-Med PMID:29078393 PubMed Central PMC5692592.

Mechanisms for U2AF to define 3' splice sites and regulate alternative splicing in the human genome.

Shao, C, Yang, B, Wu, T, Huang, J, Tang, P, Zhou, Y et al. Nat Struct Mol Biol. 2014;21 (11):997-1005. doi: 10.1038/nsmb.2906. PubMed PMID:25326705 PubMed Central PMC4429597.

See the full list of all Dr. Wu’s publications

Chase Kessinger, Ph.D.

Thank You

You Can Help Fund the Wu Lab at MMRI

When you donate to the Wu Lab at MMRI, you’re helping to fund cutting-edge research projects aimed at improving the lives of those suffering from LVNC, a relatively rare but devastating heart disease that mostly affects young children. Your donation allows MMRI to focus on propelling medical science, empowering scientists to take risks, sharing ideas and building an inclusive community.

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Chase Kessinger, Ph.D.