Our lab focuses on the translation of novel cellular and genetic therapy. Our group is composed of molecular biologists, cell biologists, biochemists and non-invasive imaging specialists. We are applying tools to study the biology of stem cells, better understand stem cell immunogenicity and tumorigenicity, derive stem cells from adult cells, and identify novel therapeutic targets.
If you are interested in a predoctoral or postdoctoral position in the lab, please contact Dr. Joseph Wu.
We have made seminal discoveries on how human induced pluripotent stem cells (iPSCs) can be used to model mechanisms of inherited cardiomyopathies, channelopathies, and other acquired cardiovascular diseases. iPSCs can also be used to identify loci or pathways related to disease predisposition via genome editing techniques (e.g., CRISPR/Cas9), thus enabling genotype-phenotype correlations, and improve risk stratification and disease management. Representative publications include: Sun et al, Science Transl Med 2012; Lan et al, Cell Stem Cell 2013; Burridge et al, Nature Methods 2014; Lee et al, Nature 2019.
Genomics and Epigenomics
Human ESCs and iPSCs are defined by their self-renewal and pluripotency potential. My lab has been working on human ESCs since 2004 and on human iPSCs since 2008. We have made several seminal contributions to the field. We are interested in understanding the genomic and epigenetic landscape changes during reprogramming, differentiation, development, and in response to various stress factors or environmental stimuli. Representative publications include Zhao et al, PNAS 2017; Churko et al, Nat Biomed Eng 2017; Churko et al, Nature Comm 2018; Lee et al, Cell Stem Cell 2018; Paik et al, Circulation 2020; Wilson et al, Dev Cell.
Pharmacogenomics and Drug Discovery
Drug discovery is an arduous and expensive process. On average, new drug requires more than $1.8 billion and 12 years from the time of discovery to commercial launch. Taking a cue from the Precision Medicine Initiative, we have been focusing on how we can use human iPSCs combined with human genomics to better understand pharmacogenomics and hence accelerate drug discovery. Representative publications include: Liang et al, Circulation 2013; Mordwinkin et al, JAMA 2013, Wilson et al, JAMA 2015; Burridge et al, Nature Medicine 2016; Sharma et al, Science Transl Med 2017; Zhang et al, Cell Stem Cell 2019.
Precision medicine seeks to link molecular data with the clinical disease phenotypes and to identify patient subpopulations that differ in their disease susceptibility, progression, and prognosis. Instead of one-drug-fits-all model, the ultimate goal is to customize prevention and treatment tailored for individual patient. My lab has been integrating genomics, transcriptomics, proteomics, metabolomics, bioinformatics, and imaging to exactly answer this question. Representative publications include Ebert et al, Science Transl Med 2014; Wu et al, Cell Stem Cell 2015, Matsa et al, Cell Stem Cel 2016; Sayed et al, Science Transl Med 2020.
Clinical trials using adult stem cells (e.g., BMSCs, MSCs, CPCs) for post-myocardial infarction patients have been intensively investigated. However, the challenges for using ESC- or iPSC-based cardiac therapies are significantly greater given the hurdles of tumorigenicity, immunogenicity, safety monitoring, and cost-effectiveness. We have performed several seminal studies addressing these specific areas ranging from basic to clinical arenas. Representative publications include Vrtovec et al, Circ Res 2013; Vrtovec et al, Circulation 2013; Nguyen et al, JAMA Cardiol 2016; Vrtovec et al, Circ Res 2018; Lee et al, Nat Biomed Eng 2018.
The efficacy of cell and gene therapy remains uncertain and has many unanswered questions. These include the following: 1) What are the molecular and cellular factors that affect myocardial improvement? (2) What are the optimal cellular and/or genetic therapies, delivery times and techniques, and dosage? (3) Do these transplanted or genetically modified cells survive, integrate, and proliferate in the target organ? (4) In the long-term, do these cells engraft, differentiate, and/ or proliferate? To address these important questions, we apply various in vivo imaging techniques including microSPECT/CT/PET, fluorescence, small animal MRI, bioluminescence, and ultrasound to track cell and gene therapy. Representative publications include Nguyen et al, Circ Res 2011; Chen et al, Circulation 2011; Nguyen et al, Cell Stem Cell 2014; Qin et al, Adv Funct Mater 2018.
Immunogenicity and iPSC Cancer Vaccine
Over a century ago, it was reported that immunization with embryonic/fetal tissue could lead to the rejection of transplanted tumors in animals. Recently, we have shown that cancers and iPSCs share many overlapping oncofetal antigens. In several models (melanoma, breast cancer, pancreatic cancer, mesothelioma), we demonstrated efficacy of iPSC-based cancer vaccine as both prophylactic and therapeutic treatment. Our goal is to further develop the concept of using autologous iPSCs for various other types of cancer models. Representative publications include Pearl et al, Cell Stem Cell 2011; de Almeida et al, Nat Comm 2014; Kooreman et al, Cell Reports 2017; Kooreman et al, Cell Stem Cell 2018.