A5030593970- Synthesis and properties of polymers
- Cancer, Hypoxia, and Metabolism
- Click Chemistry and Applications
- Ultrasound and Hyperthermia Applications
- RNA Interference and Gene Delivery
- Synthesis and Characterization of Heterocyclic Compounds
- Biopolymer Synthesis and Applications
- Protein Degradation and Inhibitors
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Fibroblast Growth Factor Research
- RNA modifications and cancer
- Synthesis and Biological Evaluation
- Adipose Tissue and Metabolism
- HER2/EGFR in Cancer Research
- Neuroscience and Neural Engineering
- DNA and Nucleic Acid Chemistry
- Histone Deacetylase Inhibitors Research
- Microfluidic and Bio-sensing Technologies
- Multiple Myeloma Research and Treatments
- Cancer-related Molecular Pathways
- Historical and Cultural Studies of Poland
- Photoreceptor and optogenetics research
Rice University
2020-2024
California Institute of Technology
2013-2024
University of California, Los Angeles
2013
Universitat Politècnica de València
2011
Universitat de València
2011
Massachusetts Institute of Technology
2009-2010
We introduce a family of protein nanoparticles capable sensing analytes in conjunction with magnetic resonance imaging (MRI). The new sensors are derived from the iron storage ferritin (Ft); they designed and optimized using facile engineering methods, self-assembled cells harboring specific combinations DNA coding sequences. As illustration, we show that suitably constructed Ft-based can report activity important neural signaling enzyme kinase A (PKA). Phosphorylation engineered by PKA...
Abstract Pyrrole-imidazole (Py–Im) polyamides are a class of programmable DNA minor groove binders capable modulating the activity DNA-binding proteins and affecting changes in gene expression. Estrogen receptor alpha (ERα) is ligand-activated hormone that binds as homodimer to estrogen response elements (ERE) driving oncogene majority breast cancers. We tested selection structurally similar Py–Im with differing sequence specificity for against 17β-estadiol (E2)–induced transcription...
A hairpin pyrrole-imidazole polyamide (1) targeted to the androgen receptor consensus half-site was found exert antitumor effects against prostate cancer xenografts. previous animal study showed that 1, which has a chiral amine at α-position of γ-aminobutyric acid turn (γ-turn), did not exhibit toxicity doses less than 10 mg/kg. In same study, with an acetamide β-position γ-turn resulted in morbidity 2.3 To identify structural motifs cause toxicity, we synthesized polyamides 1–4 variations...
Subcutaneous xenografts represent a popular approach to evaluate efficacy of prospective molecular therapeutics in vivo. In the present study, C-14 labeled radioactive pyrrole–imidazole (Py-Im) polyamide 1, targeted 5′-WGWWCW-3′ DNA sequence, was evaluated with regard its uptake properties subcutaneous xenografts, derived from human tumor cell lines LNCaP (prostate), A549 (lung), and U251 (brain), respectively. Significant variation compound concentrations seen these three lines. Influence...
Abstract Multiple myeloma is incurable and invariably becomes resistant to chemotherapy. Although the mechanisms remain unclear, hypoxic conditions in bone marrow have been implicated contributing multiple progression, angiogenesis, resistance These effects occur via adaptive cellular responses mediated by hypoxia-inducible transcription factors (HIF), targeting HIFs can anticancer both solid hematologic malignancies. Here, it was found that most cell lines tested, HIF1α, but not HIF2α...
Hypoxic gene expression contributes to the pathogenesis of many diseases, including organ fibrosis, age-related macular degeneration, and cancer. Hypoxia-inducible factor-1 (HIF1), a transcription factor central hypoxic expression, mediates multiple processes neovascularization, cancer metastasis, cell survival. Pyrrole-imidazole polyamide 1: has been shown inhibit HIF1-mediated in culture but its activity vivo was unknown. This study reports subcutaneous tumors capable mounting response...
Gene expression is a critical component of brain physiology, but monitoring this in the living represents major challenge. Here, we introduce new paradigm called recovery markers through insonation (REMIS) for noninvasive measurement gene with cell type, spatial, and temporal specificity. Our approach relies on engineered protein that are produced neurons exit into brain’s interstitium. When ultrasound applied to targeted regions, it opens blood-brain barrier releases these bloodstream. Once...
ABSTRACT Targeted gene delivery to the brain is a critical tool for neuroscience research and has significant potential treat human disease. However, site-specific of common vectors such as adeno-associated viruses (AAVs) typically performed via invasive injections, limiting their scope clinical applications. Alternatively, focused ultrasound blood-brain-barrier opening (FUS-BBBO), noninvasively, enables entry AAVs into from systemic circulation. when used in conjunction with natural AAV...
ABSTRACT Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such often affect large brain regions. Moreover, applicability FUS-BBBO in treatment brain-wide has not yet been evaluated. Herein, we evaluated transduction efficiency and safety opening up 105 sites simultaneously. Increasing number targeted increased gene delivery at each site. We achieved 60% cells with comparable majority...
Acoustically Targeted Chemogenetics (ATAC) allows for the noninvasive control of specific neural circuits. ATAC achieves such through a combination focused ultrasound (FUS) induced blood-brain barrier opening (FUS-BBBO), gene delivery with adeno-associated viral (AAV) vectors, and activation cellular signaling engineered, chemogenetic, protein receptors their cognate ligands. With ATAC, it is possible to transduce both large small brain regions millimeter precision using single application....
ABSTRACT Neurological and psychiatric diseases often involve the dysfunction of specific neural circuits in particular regions brain. Existing treatments, including drugs implantable brain stimulators, aim to modulate activity these circuits, but are typically not cell type-specific, lack spatial targeting or require invasive procedures. Here, we introduce an approach modulating noninvasively with spatial, cell-type temporal specificity. This approach, called acoustically targeted...
Acoustically Targeted Chemogenetics (ATAC) allows for the noninvasive control of specific neural circuits. ATAC achieves such through a combination focused ultrasound (FUS) induced blood-brain barrier opening (FUS-BBBO), gene delivery with adeno-associated viral (AAV) vectors, and activation cellular signaling engineered, chemogenetic, protein receptors their cognate ligands. With ATAC, it is possible to transduce both large small brain regions millimeter precision using single application....
Blood tests are among the most common clinical tools due to their low cost, simplicity, and ability observe many markers at once. However, currently, blood can only monitor a fraction of physiological processes that happen have serum marker. Here, we will present our work on development synthetic track gene expression in intact brain cells with simple test. The marker approach has several advantages. First, detection existing may be challenging levels blood. With marker, one design reporter...
ABSTRACT Understanding transcription profiles of living tissues is critical for biology and medicine. However, measurement the transcript levels typically done in homogenized post-mortem. Here, we present a new platform that enables non-invasive monitoring specific mRNA vivo , without tissue destruction. We achieved this by combining two cutting-edge tools - synthetic serum markers, called Released Markers Activity ( RMAs ), RNA-based sensors transcription. call IN-vivo Tracking ACtive...