Welcome to the Chun Liu Lab
The iPSC-Perturbation Lab is focused on using stem cell research and high-throughput CRISPR screen to better understand the mechanisms of heart disease and develop new treatments. At the core of our lab's work are Induced Pluripotent Stem Cells (iPSCs) and CRISPR screening technology. Using iPSCs, we're creating patient-specific models to delve deep into the mysteries of the heart. And with the high-throughput of CRISPR screening, we're identifying novel drug targets faster than ever before.
Our Mission
To reprogram cells to repair damaged heart tissue or even prevent cardiovascular diseases before they strike. Read about our current research:
Induced Pluripotent Stem Cells
Induced pluripotent stem cells (iPSCs) are similar to the cells in an early-stage embryo, having the potential to become any cell type in the body. We create iPSCs by taking patient blood cells and "reprogramming" them using specific genes. These reprogrammed cells can then be guided to differentiate into specific heart cells, such as muscle cells for pumping or electrical cells for rhythm control. This process mimics the natural development in an embryo. Beyond the heart, iPSCs can also differentiate into other types of cells like those in the brain or liver. This technology is crucial for studying diseases and developing new treatments.
Disease Modeling
Induced pluripotent stem cells (iPSCs) are used to model heart diseases by turning them into heart tissue that mimics patient-specific conditions. CRISPR technology allows for targeted genetic edits in these iPSCs to study the role of specific genes in heart diseases. After editing, the iPSCs are differentiated into heart cells to observe the effects. This method is invaluable for understanding disease mechanisms and testing new treatments. In the emerging field of cardio-oncology, iPSCs also help us understand how cancer drugs impact heart health, aiming to balance effective cancer treatment with minimized cardiac risks.
CRISPRi/a Screening
CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) are high-throughput screening methods that enable large-scale exploration of gene function. Utilizing libraries of single-guide RNAs (sgRNAs), these techniques can target a vast number of genes simultaneously. CRISPRi silences genes, while CRISPRa activates them, without cutting the DNA. The large-scale nature of these screens allows us to rapidly identify key genes involved in specific biological processes or diseases. By observing the effects in cells, such as growth patterns or response to drugs, we can pinpoint critical genes, thereby accelerating the pace of research and the discovery of potential new treatments.
Perturb-seq in Organoid
In the study of heart disease, heart organoids derived from induced pluripotent stem cells (iPSCs) are game-changers. These 3D mini-heart models closely mimic the complexity of the human heart, making them invaluable for research. When combined with Perturb-seq, a technique that merges CRISPR gene editing with single-cell RNA sequencing, we can map the transcriptional effects of genetic perturbations at single-cell resolution. Combining CRISPR-based genetic screening with information-rich, single-cell RNA-sequencing phenotypes allows for an exceptionally detailed understanding of disease mechanisms and revolutionize the way to identify druggable targets.
Population-in-a-Dish
The "population-in-a-dish" approach uses a large collection of iPSC lines derived from a diverse group of patients to study diseases and drug effects at a population level. Each patient-derived iPSC line can be differentiated into relevant cell types, such as heart cells for studying cardiovascular diseases. By exposing these cells to drugs or other treatments, we can assess a range of responses across different genetic backgrounds. This enables the identification of commonalities and differences in how genes contribute to disease mechanisms and treatment outcomes. The method mimics population-level studies but with the added benefit of controlled, in vitro conditions, significantly advancing personalized medicine.
Chun Liu Lab Image Gallery
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Recent Publications
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(Belbachir N, Wu Y, Shen M, Zhang SL, Zhang JZ, Liu C, Knollmann BC, Lyon GJ, Ma N, Wu JC.) Circulation. 2023 Nov 14;148(20):1598-1601 PMID: 37956223 PMCID: PMC10697282 11/13/2023
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(Colville A, Liu JY, Rodriguez-Mateo C, Thomas S, Ishak HD, Zhou R, Klein JDD, Morgens DW, Goshayeshi A, Salvi JS, Yao D, Spees K, Dixon SJ, Liu C, Rhee JW, Lai C, Wu JC, Bassik MC, Rando TA.) Cell Metab. 2023 Oct 03;35(10):1814-1829.e6 PMID: 37699398 PMCID: PMC10597643 09/13/2023
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(Shen M, Zhao SR, Khokhar Y, Li L, Zhou Y, Liu C, Wu JC.) STAR Protoc. 2023 Apr 27;4(2):102256 PMID: 37119139 PMCID: PMC10173856 04/29/2023
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(Shen M, Liu C, Zhao SR, Manhas A, Sundaram L, Ameen M, Wu JC.) Circulation. 2023 Feb 07;147(6):515-518 PMID: 36745700 PMCID: PMC9909621 02/07/2023
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(Ye S, Wang C, Xu Z, Lin H, Wan X, Yu Y, Adhicary S, Zhang JZ, Zhou Y, Liu C, Alonzo M, Bi J, Ramirez-Navarro A, Deschenes I, Ma Q, Garg V, Wu JC, Zhao MT.) Circ Res. 2023 Jan 20;132(2):187-204 PMID: 36583388 PMCID: PMC9852089 12/31/2022
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(Chun Liu, Mengcheng Shen, Wilson L. W. Tan, Ian Y. Chen, Yu Liu, Xuan Yu, Huaxiao Yang, Angela Zhang, Yanxia Liu, Ming-Tao Zhao, Mohamed Ameen, Mao Zhang, Eric R. Gross, Lei S. Qi, Nazish Sayed & Joseph C. Wu.) Nature Cardiovascular Research. (2023). https://doi.org/10.1038/s44161-023-00267-1 05/08/2023
News from the Chun Liu Lab
Dr. Liu is AHA BCVS Outstanding Early Career Faculty Finalist
MCW Cancer Center Award
Second Century Early Faculty Independence Award
Getting Involved
Postdocs and Visiting Scholars
We are always looking for talented postdoc and scholars to join our innovative projects. If you're interested in iPSC, CRISPR screening, and cardiovascular diseases, contact Dr. Liu directly for details at chunliu@mcw.eduPhD Students
Prospective PhD students interested in joining my research group should apply directly to the Physiology PhD program or contact me before your application. The Department at MCW is committed to supporting all new PhD students with five years of funding through combinations of grants, university fellowships, and teaching assistantships.Why join our iPSC-Perturbation lab?
The rapid advancements in iPSC stem cell technology and CRISPR technology have thrust us into an era where science fiction becomes reality, offering tantalizing possibilities like eradicating genetic diseases, enhancing human capabilities, and potentially extending lifespan. "Designing babies" using pluripotent stem cells and CRISPR? The concept of "modified human" could easily slide from medically justifiable edits to "designer baby", it is "feasible" today and become a rising question needs regulation and oversight. But in our lab, we are using iPSC and CRISPR tools to revolutionize medicine by curing intractable diseases and possibly even addressing the age-old problem in heart attack.Our Team
Chun Liu, PhD
Assistant Professor
Wenjing Dong, PhD
Postdoctoral Researcher
Jake R. Minx, BS
Research Technologist
Coneria Nansubuga
Graduate Student
Contact Us
The iPSC-Perturbation Lab is part of the Department of Physiology and Medicine, Cardiovascular Center and Cancer Center at the 皇家华人. To contact the lab, please email Chun Liu directly.
Chun Liu Laboratory
8701 Watertown Plank Rd.
MEB 4720
Milwaukee, WI 53226
8701 Watertown Plank Rd.
MEB 4720
Milwaukee, WI 53226
