- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Cancer Genomics and Diagnostics
- Diabetes and associated disorders
- Genetics, Aging, and Longevity in Model Organisms
- Congenital Heart Disease Studies
- Hedgehog Signaling Pathway Studies
- Metabolism, Diabetes, and Cancer
- Genetic and Kidney Cyst Diseases
- Cancer-related gene regulation
- Gene Regulatory Network Analysis
- Developmental Biology and Gene Regulation
- RNA modifications and cancer
- Genetic Syndromes and Imprinting
- RNA and protein synthesis mechanisms
- Diet and metabolism studies
- Tissue Engineering and Regenerative Medicine
- Biomedical Ethics and Regulation
Kettering University
2015-2025
Memorial Sloan Kettering Cancer Center
2014-2025
New York Proton Center
2023
Developmental Studies Center
2022
University of Wisconsin–Madison
2018
Massachusetts General Hospital
2018
Harvard Stem Cell Institute
2007-2010
Harvard University
2007-2010
Howard Hughes Medical Institute
2007-2010
Cornell University
2002-2005
The intraflagellar transport (IFT) proteins Ift172/Wimple and Polaris/Ift88 the anterograde IFT motor kinesin-II are required for production maintenance of cilia. These also activation targets mouse Hedgehog (Hh) pathway by Gli transcription factors. phenotypes mutants, however, not identical to mutants that lack Smoothened (Smo), an essential activator Hh pathway. We show here embryos both Ift172 Smo single which indicates acts downstream Smo. have a weaker neural patterning phenotype than...
Understanding how cells respond differently to perturbation is crucial in cell biology, but existing methods often fail accurately quantify and interpret heterogeneous single-cell responses. Here we introduce the perturbation-response score (PS), a method diverse responses at level. Applied datasets such as Perturb-seq, PS outperforms quantifying partial gene perturbations. further enables dosage analysis without needing titrate perturbations, identifies 'buffered' 'sensitive' response...
In healthy adult mice, the beta cell population is not maintained by stem cells but instead replication of differentiated cells. It known, however, whether all contribute equally to growth and maintenance, as it may be that some replicate while others do not. Understanding precisely which are responsible for will inform attempts expand in vitro, a potential source replacement therapy treat diabetes. Two experiments were performed address this issue. First, level fluorescence generated pulse...
Transcriptional regulatory mechanisms of lineage priming in embryonic development are largely uncharacterized because the difficulty isolating transient progenitor populations. Directed differentiation human pluripotent stem cells (hPSCs) combined with gene editing provides a powerful system to define precise temporal requirements for progressive chromatin changes during cell fate transitions. Here, we map dynamic landscape associated sequential stages pancreatic from hPSCs. Our analysis...
The development of new gene-editing tools, in particular the CRISPR/Cas system, has greatly facilitated site-specific mutagenesis human embryonic stem cells (hESCs), including introduction or correction patient-specific mutations for disease modeling. However, integration a reporter gene into an endogenous locus hESCs still requires lengthy and laborious two-step strategy that involves first drug selection to identify correctly targeted clones then excision drug-resistance cassette. Through...
DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition removal of are known, but how they cooperate regulate the landscape remains a central question. Using knockin reporter, we performed genome-wide CRISPR-Cas9 screen in human embryonic stem cells discover regulators. The top hit was an uncharacterized gene, QSER1, which proved be key guardian bivalent promoters poised enhancers developmental...