- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Click Chemistry and Applications
- Virus-based gene therapy research
- Genetics, Aging, and Longevity in Model Organisms
- Peptidase Inhibition and Analysis
- Nonmelanoma Skin Cancer Studies
- Nematode management and characterization studies
- Chemical Synthesis and Analysis
- Advanced biosensing and bioanalysis techniques
- Circadian rhythm and melatonin
- Immune Cell Function and Interaction
- Gut microbiota and health
- Photodynamic Therapy Research Studies
- Corneal Surgery and Treatments
- Cancer Immunotherapy and Biomarkers
- Advanced Biosensing Techniques and Applications
- Oral and Maxillofacial Pathology
- Nanoparticle-Based Drug Delivery
- Angiogenesis and VEGF in Cancer
- Synthetic Organic Chemistry Methods
- Metalloenzymes and iron-sulfur proteins
- Protease and Inhibitor Mechanisms
- Sinusitis and nasal conditions
- Ear Surgery and Otitis Media
Stanford University
2015-2024
Max Planck Institute for Developmental Biology
2014-2018
Cornell University
2011-2018
Center for Medical, Agricultural and Veterinary Entomology
2011
United States Department of Agriculture
2011
Columbia University Irving Medical Center
2009
In the model organism Caenorhabditis elegans, a family of endogenous small molecules, ascarosides function as key regulators developmental timing and behavior that act upstream conserved signaling pathways. The are based on dideoxysugar ascarylose, which is linked to fatty-acid-like side chains varying lengths derived from peroxisomal β-oxidation. Despite importance for many aspects C. elegans biology, knowledge their structures, biosynthesis, homeostasis remains incomplete. We used an...
Chemistry the worm's way: The nematode Pristionchus pacificus constructs elaborate small molecules from modified building blocks of primary metabolism, including an unusual xylopyranose-based nucleoside (see scheme). These compounds act as signaling to control adult phenotypic plasticity and dauer development provide examples modular generation structural diversity in metazoans.
Significance Early detection by white-light endoscopy (WLE) is the key procedure used in clinical care to prevent colorectal cancer (CRC). In high-risk patients develop CRC, like inflammatory bowel disease, miss-rate of dysplastic lesions three times higher compared healthy individuals. this study we explored use a near-infrared probe with fluorescence as an adjunct WLE highlight adenomas. We demonstrated clinically relevant animal models carcinogenesis and ulcerative colitis that our...
<b>Objective:</b> To investigate transcranial magnetic stimulation (TMS) measures as clinical correlates and longitudinal markers of amyotrophic lateral sclerosis (ALS). <b>Methods:</b> We prospectively studied 60 patients with ALS subtypes (sporadic ALS, familial progressive muscular atrophy, primary sclerosis) using single pulse TMS, recording from abductor digiti minimi (ADM) tibialis anterior (TA) muscles. evaluated three measures: 1) TMS motor response threshold to the ADM, 2) central...
Nematodes use an extensive chemical language based on glycosides of the dideoxysugar ascarylose for developmental regulation (dauer formation), male sex attraction, aggregation, and dispersal. However, no examples a female- or hermaphrodite-specific attractant have been identified to date. In this study, we investigated pheromone system gonochoristic sour paste nematode Panagrellus redivivus , which produces sex-specific attractants opposite sex. Activity-guided fractionation P....
Molecularly targeted optical contrast agents have the potential to enable surgeons visualize specific molecular markers that can help improve surgical precision and thus outcomes. Fluorescently quenched substrates be used highlight tumor lesions by targeting proteases are highly abundant in microenvironment. However, majority of these other molecularly labeled with reporter dyes not ideally matched properties clinical camera systems, which typically optimized for detection indocyanine-green...
We describe a new type of collective behavior in C. elegans nematodes, aggregation starved L1 larvae. Shortly after hatching the absence food, larvae arrest their development and disperse search for food. In contrast, two or more days without worms change behavior--they start to aggregate. The requires small amount ethanol acetate environment. case ethanol, it has be metabolized, which functional alcohol dehydrogenase sodh-1. resulting is used de novo fatty acid synthesis, some newly made...
Abstract Purpose The reoperation rate for breast-conserving surgery is as high 15–30% due to residual tumor in the surgical cavity after surgery. In vivo tumor-targeted optical molecular imaging may serve a red-flag technique improve intraoperative margin assessment and reduce rates. Cysteine cathepsins are overexpressed most solid types, including breast cancer. We developed cathepsin-targeted, quenched fluorescent activity-based probe, VGT-309, evaluated whether it could be used detection...
Fluorescently quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection, and surgical guidance. These often designed to target specific enzymes associated with diseases by direct optimization using single purified enzymes. However, this can result painstaking chemistry efforts produce a probe suboptimal performance when applied vivo. We describe here an alternate, unbiased activity-profiling approach which...
A cross metathesis (CM)-based synthesis of the caeliferins, a family sulfooxy fatty acids that elicit plant immune responses, is reported. Unexpectedly, detailed NMR spectroscopic and mass spectrometric analyses CM reaction mixtures revealed extensive isomerization homologation starting materials products. It shown degree in strongly correlates with substrate chain length lipophilicity. Side-product suppression requires appropriate catalyst selection use 1,4-benzoquinone as hydride scavenger.
Keratinocyte carcinomas, including basal and squamous cell are the most common human cancers worldwide. While 75% of all keratinocyte carcinoma (4 million annual cases in United States) treated with conventional excision, this surgical modality has much lower cure rates than Mohs micrographic surgery, likely due to bread-loaf histopathologic assessment that visualizes <1% tissue margins. A quenched protease-activated fluorescent probe 6qcNIR, which produces a signal only protease-rich tumor...
Otitis media (OM) or middle ear infection is one of the most common diseases in young children around world. The diagnosis OM currently performed using an otoscope to detect fluid and inflammatory changes manifested tympanic membrane. However, conventional otoscopy cannot visualize across membrane sample fluid. This can lead low diagnostic certainty overdiagnoses OM. To improve OM, we have developed a short-wave infrared (SWIR) combination with protease-cleavable biosensor, 6QC-ICG, which...
In the nematode model organisms Caenorhabditis elegans and Pristionchus pacificus, a new class of natural products based on modular assembly primary-metabolism-derived building blocks control organismal development behavior. We report identification biological activities first pentamodular metabolite, pasa#9, 8-oxoadenine-containing npar#3 from P. pacificus. These structures suggest co-option nucleoside tryptophan metabolic pathways for biosynthesis endogenous metabolite libraries that...
Aus modifizierten Bausteinen des Primärmetabolismus, darunter auch ein ungewöhnliches Xylopyranose-Nucleosid (siehe Schema), baut der Nematode Pristionchus pacificus niedermolekulare Substanzen auf, die als Signalmoleküle Entwicklung und Elastizität adulten Phänotyps lenken. Sie sind Beispiele für modulare Erzeugung struktureller Diversität in Metazoen. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not...
ABSTRACT Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become standard care cancer surgeries. One the key parameters optimize agent is molecular size, which dictates much pharmacokinetic pharmacodynamic properties agent. Here, we describe development a class protease-activated...
Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become the standard care cancer surgeries. One key parameters optimize is molecular size, which dictates much pharmacokinetic pharmacodynamic properties agent. Here, we describe development a class protease-activated quenched fluorescent...