- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Acute Lymphoblastic Leukemia research
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Plant Molecular Biology Research
- RNA modifications and cancer
- Hedgehog Signaling Pathway Studies
- Neuroblastoma Research and Treatments
- Craniofacial Disorders and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Microtubule and mitosis dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cleft Lip and Palate Research
- Molecular Biology Techniques and Applications
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Hippo pathway signaling and YAP/TAZ
- Genomic variations and chromosomal abnormalities
Children's Mercy Hospital
2024
Mercy Research
2021-2024
Stowers Institute for Medical Research
2016-2024
Mercy Hospital
2024
Michigan State University
2014-2016
Enhancers constitute one of the major components regulatory machinery metazoans. Although several genome-wide studies have focused on finding and locating enhancers in genomes, fundamental principles governing their internal architecture cis-regulatory grammar remain elusive. Here, we describe an extensive, quantitative perturbation analysis targeting dorsal-ventral patterning gene network (GRN) controlled by Drosophila NF-κB homolog Dorsal. To understand transcription factor interactions...
Hoxa1 has diverse functional roles in differentiation and development. We identify characterize properties of regions bound by HOXA1 on a genome-wide basis differentiating mouse ES cells. HOXA1-bound are enriched for clusters consensus binding motifs HOX, PBX, MEIS, many display co-occupancy PBX MEIS. MEIS members the TALE family analysis multiple (PBX, TGIF, PREP1, PREP2) shows that nearly all targets occupancy one or more members. The combinatorial patterns proteins define distinct classes...
ABSTRACT A core framework of the gene regulatory network (GRN) governing neural crest (NC) cell development has been generated by integrating separate inputs from diverse model organisms rather than direct comparison. This limited insights into diversity genes in NC GRN and extent conservation newly identified transcriptional signatures differentiation invasion. Here, we address this leveraging strengths accessibility avian embryo to precise developmental staging egg incubation use an...
HiC sequencing is a DNA-based next-generation method that preserves the 3D conformation of genome and has shown promise in detecting genomic rearrangements translational research studies. To evaluate as potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia sarcoma specimens previously positive for clinically significant rearrangements. Archived specimen types tested included viable nonviable frozen...
Hi-C sequencing is a DNA-based next-generation method that preserves the 3D genome conformation and has shown promise in detecting genomic rearrangements translational research studies. To evaluate as potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia sarcoma specimens. Archived viable non-viable frozen leukemic cells formalin-fixed paraffin-embedded (FFPE) tumor specimens were analyzed. Pediatric acute...
Abstract Pre-cancerous cells are normally recognized and eliminated by immune cells. Cancer progresses only when this immunosurveillance system fails. Although immunotherapy has driven the most significant exciting advances in cancer treatment modern times, current approaches running into barriers. An emerging area of interest includes evidence for rare but highly potent stem cell-like T Stem-like combine long-term persistence high potency with immunological memory. Our recent findings...
Abstract Hoxa1 has diverse functional roles in differentiation and development. We have identified characterized properties of regions bound by on a genome-wide basis differentiating mouse ES cells. are enriched for clusters consensus binding motifs Hox, Pbx Meis many display co-occupancy Meis. members the TALE family analysis multiple (Pbx, Meis, TGIF, Prep1 Prep2) show that nearly all targets occupancy one or more members. The combinatorial patterns proteins defines distinct classes...
Abstract Hox genes play a key role in head formation by specifying the axial identity of neural crest cells (NCCs) migrating into embryonic pharyngeal arches. In absence Hoxa2 , NCC derivatives second arch (PA2) undergo homeotic transformation and duplicate structures formed first (PA1) NCCs. Current models postulate that PA1 represents ‘ground state’ loss causes reversion PA2 NCCs to state’. We use bulk single-cell RNAseq investigate molecular mechanisms driving this phenotypic mouse. -/-...
Craniofacial structures are shaped by the formation, migration, and differentiation of cranial neural crest cells (cNCCs) in developing embryo. Many craniofacial defects caused misregulation this embryonic cell population. Recent work has identified key components gene regulatory network (GRN) responsible for cNCC development, but there remain gaps our knowledge. One such example is Hox family genes, which known to pattern subsets cNCCs show jaw, ear, palate when misexpressed, yet whose role...
Abstract Two-thirds of infants diagnosed with acute lymphoblastic leukemia (ALL) KMT2A gene rearrangement (KMT2A-r) relapse; however, the biological mechanisms underlying this relapse are unknown. Relapsed infant ALL carries a particularly poor prognosis and is often resistant to further attempts at re-induction. Here, we use single-cell RNA sequencing (scRNAseq) data on samples collected diagnosis from KMT2A-r patients identify genes differentially expressed between cases known later versus...