A5035769655- Genomics and Chromatin Dynamics
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Genetic and rare skin diseases.
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- Tumors and Oncological Cases
- Transplantation: Methods and Outcomes
- T-cell and B-cell Immunology
- Cardiac Fibrosis and Remodeling
- Cytomegalovirus and herpesvirus research
- Developmental Biology and Gene Regulation
- Nuclear Structure and Function
- Cardiomyopathy and Myosin Studies
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- melanin and skin pigmentation
- Long-Term Effects of COVID-19
- Skin and Cellular Biology Research
- Colorectal and Anal Carcinomas
Stanford University
2019-2025
Patient-specific iPSCs model endothelial dysfunction in lamin A and C–related dilated cardiomyopathy identify lovastatin as a therapy.
Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms Smoothened (SMO) inhibitor resistance. We previously identified nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, characteristics drivers the nMRTF state unknown. Here, we use single RNA-sequencing patient tumors identify...
Abstract Cancer immunotherapies have revolutionized treatment but shown limited success as single-agent therapies highlighting the need to understand origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell imaging-based spatial analysis elucidate three microenvironmental neighborhoods surrounding basal cell carcinoma epithelia. Within highly proliferative neighborhood, find that TREM2 + skin cancer-associated macrophages (SCAMs) support proliferation a...
Summary Regulation of gene expression hinges on the interplay between enhancers and promoters, traditionally explored through pairwise analyses. Recent advancements in mapping genome folding, like GAM, SPRITE, multi-contact Hi-C, have uncovered multi-way interactions among super-enhancers (SEs), spanning megabases, yet not measured their frequency single cells or relationship clustering transcription. To close this gap, here we used multiplexed imaging to map 3D positions 376 SEs across...
Abstract We present Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a scalable platform producing autologous organotypic iPS cell-derived induced skin composite (iSC) grafts for definitive treatment. Clinical-grade manufacturing integrates CRISPR-mediated genetic correction with reprogramming into one step, accelerating derivation of COL7A1 -edited cells from patients. Differentiation epidermal, dermal and melanocyte progenitors is followed by CD49f-enrichment, minimizing maturation...
Memory T cells exhibit considerable diversity that determines their ability to be protective. Here, we examine whether changes in cell heterogeneity contribute the age-associated failure of immune memory. By screening for age-dependent cell-surface markers, identify CD4 and CD8 memory subsets are unrelated previously defined central effector cells. expressing ecto-5'-nucleotidase CD73 constitute a functionally distinct subset declines with age. They resemble long-lived, polyfunctional but...
Summary Background Gene editing in induced pluripotent stem (iPS) cells has been hailed to enable new cell therapies for various monogenetic diseases including dystrophic epidermolysis bullosa (DEB). However, manufacturing, efficacy and safety roadblocks have limited the development of genetically corrected, autologous iPS cell-based therapies. Methods We developed Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a generation GMP-compatible (cGMP), reproducible, scalable platform...
While squamous transdifferentiation within subpopulations of adenocarcinomas represents an important drug resistance problem, its underlying mechanism remains poorly understood. Here, using surface markers resistant basal cell carcinomas (BCCs) and patient single-cell bulk transcriptomic data, we uncover the dynamic roadmap to carcinoma transition (BST). Experimentally induced BST identifies activator protein 1 (AP-1) family members in regulating tumor plasticity, show that c-FOS plays a...
Ectodermal dysplasias including skin abnormalities and cleft lip/palate result from improper surface ectoderm (SE) patterning. However, the connection between SE gene regulatory networks disease remains poorly understood. Here, we dissect human differentiation with multiomics establish GRHL2 as a key mediator of early commitment, which acts by skewing cell fate away neural lineage. master regulator AP2a balance output, facilitating binding to loci. In turn, restricts DNA de novo chromatin...
Improved response to canonical therapies requires a mechanistic understanding of dynamic tumor heterogeneity by identifying discrete cellular populations with enhanced plasticity. We have previously demonstrated distinct resistance mechanisms in skin basal cell carcinomas, but comprehensive the states and markers associated these remains poorly understood. Here we identify pre-existing resistant population naive carcinoma tumors marked surface marker LY6D. LY6D
Abstract Background Cardiomyopathies are a leading cause of progressive heart failure and sudden cardiac death; however, their genetic aetiology remains poorly understood. We hypothesised that variants in noncoding regulatory regions oligogenic inheritance mechanisms may help close the diagnostic gap. Methods first analysed whole-genome sequencing data 143 parent–offspring trios from Genomics England 100,000 Genomes Project. used gene panel testing phenotype-based, variant prioritisation...
The repurposing of biomedical data is inhibited by its fragmented and multi-formatted nature that requires redundant investment time resources scientists. This particularly true for Type 1 Diabetes (T1D), one the most intensely studied common childhood diseases. Intense investigation contribution pancreatic β-islet T-lymphocytes in T1D has been made. However, genetic contributions from B-lymphocytes, which are known to play a role subset patients, remain relatively understudied. We have...
Abstract Memory T cells exhibit considerable diversity that determines their ability to be protective and durability. Here, we examined whether changes in cell heterogeneity contribute the age-associated failure of immune memory. By screening for age-dependent surface markers, have identified CD4 CD8 memory subsets are unrelated previously defined central effector cells. expressing ecto-5’-nucleotidase CD73 constitute a functionally distinct subset declines with age. They many features...
Heart transplantation continues to be a life-saving therapy for patients with end-stage heart failure; yet the average long-term graft survival remains at only 12.5 years. Cardiac allograft vasculopathy (CAV) and cardiac dysfunction are both key contributors morbidity mortality in transplant population. Studies have suggested that immunosuppressive agents may modulate cardiovascular function, mechanisms this modulation is incompletely understood. The primary classes of utilized post-heart...
ABSTRACT While basal cell carcinomas (BCCs) arise from ectopic hedgehog pathway activation and can be treated with inhibitors, sporadic BCCs display high resistance rates while tumors arising in Gorlin syndrome patients germline Patched ( PTCH1 ) mutations are uniformly suppressed by inhibitor therapy. In rare cases, on long-term therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this remains unstudied. Here we report a case an SMO i -resistant...
ABSTRACT Human pluripotent stem cell-derived tissue engineering offers great promise in designer cell-based personalized therapeutics. To harness such potential, a broader approach requires deeper understanding of tissue-level interactions. We previously developed manufacturing system for the ectoderm-derived skin epithelium cell replacement therapy. However, it remains challenging to manufacture endoderm-derived esophageal epithelium, despite both possessing similar stratified structure....