Research Interests
1. Gene regulation of muscle regeneration.
2. Genomics technology development.
3. Genetic and epigenetic control of rhabdomyosarcoma.
2. Genomics technology development.
3. Genetic and epigenetic control of rhabdomyosarcoma.
Selected Grants
Engineering Heterocellular Human Skeletal Muscle Tissues to Recreate and Study Native Stem Cell Niche Function
ResearchCollaborator · Awarded by National Institutes of Health · 2024 - 2029Chromatin dysregulation in neurodevelopmental disorders
ResearchCollaborator · Awarded by National Institutes of Health · 2024 - 2029Enhancing limb regeneration with gene therapy informed by comparative biology
ResearchCollaborator · Awarded by National Institutes of Health · 2024 - 2029Molecular Analysis of Developmental Brain Disorders Associated with Synaptic Pathology
ResearchInvestigator · Awarded by National Institute of Mental Health · 2022 - 2027Medical Scientist Training Program
Inst. Training Prgm or CMEPreceptor · Awarded by National Institute of General Medical Sciences · 2022 - 2027Localization of adenosine to promote fracture healing
ResearchCo Investigator · Awarded by National Institute on Aging · 2022 - 2027Training Program in Developmental and Stem Cell Biology
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2001 - 2027Cell and Molecular Biology Training Program
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2021 - 2026Regulation of Skeletal Muscle Fibrosis in Duchenne Muscular Dystrophy
ResearchPrincipal Investigator · Awarded by Department of Defense · 2024 - 2026Engineering Human Heart Tissues with Polyploid Cardiomyocytes
ResearchCo Investigator · Awarded by National Institutes of Health · 2022 - 2026Epigenome Editing for Stable Reactivation of Maternal PWS Genes
ResearchCo Investigator · Awarded by Foundation for Prader-Willi Research · 2024 - 2026The 4D nucleome of muscle regeneration in ischemia-induced tissue damage and repair
ResearchPrincipal Investigator · Awarded by National Heart, Lung, and Blood Institute · 2020 - 2025Multi-omics functional analysis of non-coding regulatory genome for genomic medicine
ResearchPrincipal Investigator · Awarded by National Human Genome Research Institute · 2020 - 2025Genetic and Genomics Training Grant
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2020 - 2025LIVE IMAGING OF BONE REGENERATION IN ZEBRAFISH
ResearchInvestigator · Awarded by National Institute of Arthritis and Musculoskeletal and Skin Diseases · 2020 - 2025Targeting CDK8 in fusion-positive rhabdomyosarcoma
ResearchCollaborator · Awarded by Rally! Foundation · 2021 - 20232023 Triangle Regeneration Biology Symposium
ConferencePrincipal Investigator · Awarded by North Carolina Biotechnology Center · 2023 - 2023Role of the macro lncRNA KCNQ1OT1 in embryonal rhabdomyosarcoma tumorigenesis
ResearchCollaborator · Awarded by Kate Amato Foundation Inc. · 2019 - 2023Assessing healthspan in aged mice after prolonged exposure to young circulation
ResearchCo Investigator · Awarded by National Institutes of Health · 2020 - 2023Role of the macro lncRNA KCNQ1OT1 in embryonal rhabdomyosarcoma tumorigenesis
ResearchCo Investigator · Awarded by Alex's Lemonade Stand · 2019 - 2023Study of a novel kinase and its targeted inhibitor in Rhabdomyosarcoma
ResearchPrincipal Investigator · Awarded by Elsa U. Pardee Foundation · 2020 - 2021Transcriptional regulatory network that controls fusion-positive rhabdomyosarcoma tumorigenesis
ResearchPrincipal Investigator · Awarded by V Foundation for Cancer Research · 2019 - 2021Super-resolution Imaging via Multiple Modalities with the Zeiss Elyra 7
EquipmentMinor User · Awarded by National Institutes of Health · 2020 - 2021Role of MST/Hippo kinase inactivation in driving fusion-positive rhabdomyosarcoma
FellowshipCollaborator · Awarded by National Institutes of Health · 2020 - 2021HARDAC-M: Enabling memory-intensive computation for genomics
EquipmentMajor User · Awarded by North Carolina Biotechnology Center · 2020 - 2021Organization and Function of Cellular Structure
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 1975 - 2020Identification and application of cis-regulatory enhancer elements for muscle stem cell function and muscle regeneration in aging
ResearchPrincipal Investigator · Awarded by American Federation for Aging Research · 2019 - 2020Fellowships, Gifts, and Supported Research
Functional analysis of Alzheimer’s Disease associated genetic risk variants in astrocytes ·
2019
- 2020
PI ·
Awarded by: Kahn program and Translating Duke Health
Most genome-wide association studies signals are enriched at the regulatory sequences of the genome, leading to the hypothesis that risk genetic variations contribute to diseases via affecting enhancer function. In Alzheimer’s Diseas (AD), emerging evidence suggests that the intricate balance between neurons and astrocytes becomes perturbed. However, role of astrocyte in AD is much less studied. Since the non-coding genome is less conserved between human and mouse, there is an urgent need to determine the consequences of AD risk variants in human cells, and to identify their affected genes that can be further studied in animal. In this study, we will utilize cutting-edge functional genomic approaches and human astrocyte model, to identify the causal genetic variation that affect enhancer activity in astrocyte and therefore predispose for AD. The results from this work can be used as biomarkers of AD risk and identify pathways that can be targeted for treatments.
Targeted reprogramming of human epigenome using CRISPR/Cas9 system ·
2014
- 2017
PI ·
Awarded by: The Human Frontier Science Program (HFSP)
How genetic and epigenetic mechanisms control proper gene expression is a fundamental unresolved problem. At the sequence level, enhancers regulate transcription in a cell-type- and cell-state-specific manner. On top of enhancer sequence, dynamic DNA methylation and histone modification processes have been correlated with transcription regulation. The host lab has provided the first indication that histone modification patterns can be used for enhancer annotation. However, mechanisms of enhancer regulation by chromatin modification are not completely understood, mostly due to the inability of targeted reprogramming of epigenome. Here I will develop tools which enable us to targeted edit the epigenome in human cells(Aim 1). In hESC, I will express fusion proteins containing mutant Cas9(dCas9, lacking nuclease activity) and chromatin modifying enzymes, which can be guided to target DNA sequence by sgRNA to edit chromatin modifications. Next, I will study the role of enhancer-like chromatin modification in gene regulation and cell fate determination(Aim 2). I will create H3K4me1 modification near NKX2-5 locus in hESC, a master regulator of cardiac progenitor cells, followed by monitoring changes in NKX2-5 expression, histone modification and cell fate. I will also study if chromatin modifications play a causative role in enhancer activity and transcription(Aim 3). The chromatin modifications on OCT4 enhancers in hESC will be reprogrammed by CRISPR/Cas9 system. I will then perform a rigorous genomic analysis to study the dependency between chromatin modification, OCT4 enhancer activity and hESC pluripotency. Using these data, I will explore the role chromatin modifications in enhancer regulation. I expect this project will have a major impact on the understanding of functional human epigenome and on developmental biology. The developed CRISPR/Cas9 system will be widely applicable in epigenetic studies in other model systems.