A5040756158- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
- Chromatin Remodeling and Cancer
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Gut microbiota and health
- Transgenic Plants and Applications
- Gene Regulatory Network Analysis
- Microbial Metabolic Engineering and Bioproduction
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Autophagy in Disease and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Protein Tyrosine Phosphatases
- Genetics and Neurodevelopmental Disorders
- Plant Water Relations and Carbon Dynamics
- Ubiquitin and proteasome pathways
- Clostridium difficile and Clostridium perfringens research
- Nanofabrication and Lithography Techniques
- Plant Virus Research Studies
- Testicular diseases and treatments
University of California, Irvine
2023-2025
University of California System
2025
University of Minnesota Medical Center
2024
University of Minnesota System
2024
California Institute of Technology
2019-2022
University of Minnesota
2017-2019
UC Irvine Health
2019
When nature evolves a gene over eons at scale, it produces diversity of homologous sequences with patterns conservation and change that contain rich structural, functional, historical information about the gene. However, natural accumulates slowly likely excludes large regions functional sequence space, limiting is encoded extractable. We introduce upgraded orthogonal DNA replication (OrthoRep) systems radically accelerate evolution chosen genes under selection in yeast. applied to...
In neurofibromatosis type 1 (NF1) and in highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), constitutively active RAS-GTP increased MAPK signaling are important tumorigenesis. Dual specificity phosphatases (DUSPs) negative regulators of that dephosphorylate p38, JNK, ERK different settings. Although often acting as tumor suppressors, DUSPs may also act oncogenes, helping cells adapt to high levels signaling. We hypothesized inhibiting might be selectively toxic from...
Abstract Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma CNS-PNET. Cross-species gene expression analyses classified SB-driven into distinct CNS-PNET subgroups, indicating they resemble human Sonic hedgehog group 3 4 CNS neuroblastoma FOXR2 activation. This represents the...
Multistability and hysteresis is a potential mechanism to describe shifts persistence of aerobe-anaerobe communities.
Efficient methods for diversifying genes of interest (GOIs) are essential in protein engineering. For example, OrthoRep, a yeast-based orthogonal DNA replication system that achieves the rapid vivo diversification GOIs encoded on cytosolic plasmid (p1), has been successfully used to drive numerous engineering campaigns. However, OrthoRep-based GOI evolution almost always started from single sequences, limiting number locations fitness landscape where evolutionary search begins. Here, we...
Abstract Advances in synthetic biology, bioengineering, and computation allow us to rapidly reliably program cells with increasingly complex useful functions. However, because the functions we engineer perform are typically burdensome cell growth, they can be lost due processes of mutation natural selection. Here, show that a strategy terminal differentiation improves evolutionary stability general manner by realizing reproductive metabolic division labor. To implement this strategy, develop...
Abstract Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome, caused by heterozygous loss of function mutations in the tumor suppressor gene NF1 . Individuals with develop benign tumors peripheral nervous system (neurofibromas), originating from Schwann cell linage after somatic wild type allele, some which progress further to malignant nerve sheath (MPNST). There only one FDA approved targeted therapy for symptomatic plexiform neurofibromas and none MPNST. The genetic...
We recently developed "autonomous hypermutation yeast surface display" (AHEAD), a technology that enables the rapid generation of potent and specific antibodies in yeast. AHEAD pairs display with an error-prone orthogonal DNA replication system (OrthoRep) to continuously rapidly mutate surface-displayed antibodies, thereby enabling enrichment for stronger binding variants through repeated rounds cell growth fluorescence-activated sorting. currently utilizes standard galactose induction drive...
Orthogonal replication enables rapid continuous biomolecular evolution in
When nature maintains or evolves a gene's function over millions of years at scale, it produces diversity homologous sequences whose patterns conservation and change contain rich structural, functional, historical information about the gene. However, natural gene likely excludes vast regions functional sequence space includes phylogenetic evolutionary eccentricities, limiting what we can extract. We introduce an accessible experimental approach for compressing long-term evolution to...
Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) can arise from atypical neurofibromas (ANF). Loss of the polycomb repressor complex 2 (PRC2) is a common event. Previous studies on PRC2-regulated genes in MPNST used genetic add-back experiments highly aneuploid cell lines which may miss NF1-mutant ANF-like precursor cells. A set human Schwann cells (SCs) has not been defined. We hypothesized that PRC2 loss direct and indirect effects gene expression resulting MPNST, so...
Efficient methods for diversifying genes of interest (GOIs) are essential in protein engineering. For example, OrthoRep, a yeast-based orthogonal DNA replication system that achieves the rapid vivo diversification GOIs encoded on cytosolic plasmid (p1), has been successfully used to drive numerous engineering campaigns. However, OrthoRep-based GOI evolution almost always started from single sequences, limiting number locations fitness landscape where evolutionary search begins. Here, we...
Abstract We recently developed ‘autonomous hypermutation yeast surface display’ (AHEAD), a technology that enables the rapid generation of potent and specific antibodies in yeast. AHEAD pairs display with an error-prone orthogonal DNA replication system (OrthoRep) to continuously rapidly mutate surface-displayed antibodies, thereby enabling enrichment for stronger binding variants through repeated rounds cell growth fluorescence activated sorting (FACS). currently utilizes standard galactose...
Abstract MAPK pathway activation is found across central nervous system tumors. Neurofibromin 1 (NF1) protein a GTPase-activating and tumor suppressor that negatively regulates RAS activity. A NF1 loss of function mutation results in upregulation associated with pediatric gliomas. We previously demonstrated autophagy inhibition improves response to BRAF inhibition. Here we investigate the role cells presence or absence MEK (MEKi). wild type (WT) knockout (KO) (HSC1λ, immortalized human...
Abstract Neurofibromatosis Type 1 (NF1) is a common (1:2500 births) genetic disorder and cancer predisposition syndrome, caused by mutations in the tumor suppressor gene NF1. One of known functions protein encoded NF1 (neurofibromin) that negative regulator Ras pathway signaling, through its Ras-GAP activity. Among other symptoms, individuals with often develop benign tumors peripheral nervous system (called dermal or plexiform neurofibromas), originating from Schwann cell linage their...
Abstract Advances in synthetic biology, bioengineering, and computation allow us to rapidly reliably program cells with increasingly complex useful functions. However, because the functions we engineer perform are typically unnecessary for cellular survival burdensome cell growth, they can be lost due processes of mutation natural selection. To improve evolutionary stability engineered a general manner, developed an integrase-recombination-based differentiation gene circuit Escherichia coli...
<p>Figure S4. Shows ARHGAP36 expression in mouse and human neural tissue. Figure S5. characterization of Megf10 C17.2 cells Figures S6-S7 show mechanistic analysis FOXR2 HSC1L cells</p>
<p>Figure S4. Shows ARHGAP36 expression in mouse and human neural tissue. Figure S5. characterization of Megf10 C17.2 cells Figures S6-S7 show mechanistic analysis FOXR2 HSC1L cells</p>
<div>Abstract<p>Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain with limited effective therapies. Using <i>Sleeping Beauty</i> (<i>SB</i>) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma CNS-PNET. Cross-species gene expression analyses classified <i>SB</i>-driven into distinct CNS-PNET subgroups, indicating they resemble human Sonic...
<p>Characterization of SB-induced medulloblastomas and CNS-PNETs.</p>
<p>Characterization of SB-induced medulloblastomas and CNS-PNETs.</p>