A5077237376- Amphibian and Reptile Biology
- Phytochemical compounds biological activities
- Species Distribution and Climate Change
- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Chemical Synthesis and Analysis
- Plant and animal studies
- Cell death mechanisms and regulation
- Plant biochemistry and biosynthesis
- Computational Drug Discovery Methods
- Mercury impact and mitigation studies
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Microbial Natural Products and Biosynthesis
- Ecology and Vegetation Dynamics Studies
- Wildlife Ecology and Conservation
- Animal Vocal Communication and Behavior
- Rangeland and Wildlife Management
- Toxin Mechanisms and Immunotoxins
- Paleontology and Evolutionary Biology
- Evolution and Paleontology Studies
- Animal Behavior and Reproduction
- Turtle Biology and Conservation
- RNA modifications and cancer
- Cancer-related Molecular Pathways
Boston University
2016-2025
Center for Discovery
2017-2024
Westmead Hospital
2024
Molecular Discovery (United Kingdom)
2024
Levine Children's Hospital
2023
University of Aberdeen
2023
University of Massachusetts Amherst
2020-2022
Bristol-Myers Squibb (United States)
2022
Illinois State University
1999-2021
University of Massachusetts Boston
2021
Abstract Rocaglamide has been reported to sensitize several cell types TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led generation of novel rocaglamide analogs. However, these not extensively analyzed as TRAIL sensitizers, particularly TRAIL-resistant renal carcinoma cells. Evaluation and analogs identified 29 compounds that are able ACHN cells TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated their protein synthesis inhibitors...
Abstract New strategies are needed to counter the escalating threat posed by drug-resistant fungi. The molecular chaperone Hsp90 affords a promising target because it supports survival, virulence and drug-resistance across diverse pathogens. Inhibitors of human under development as anticancer therapeutics, however, exert host toxicities that preclude their use antifungals. Seeking route species-selectivity, we investigate nucleotide-binding domain (NBD) from most common fungal pathogen,...
Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with limited treatment options. Although metabolic reprogramming hallmark of many cancers, including PDA, previous attempts to target changes therapeutically have been stymied by drug toxicity and tumour cell plasticity. Here, we show that PDA cells engage an eIF4F-dependent translation program supports redox central carbon metabolism. Inhibition the eIF4F subunit, eIF4A, using synthetic rocaglate CR-1-31-B (CR-31) reduced...
Abstract In the colon, long-term exposure to chronic inflammation drives colitis-associated colon cancer (CAC) in patients with inflammatory bowel disease. While causal and clinical links are well established, molecular understanding of how leads development is lacking. Here we deconstruct evolving microenvironment CAC by measuring proteomic changes extracellular matrix (ECM) organization over time a mouse model CAC. We detect early ECM structure composition, report crucial role for...
Abstract Tumors initiate by mutations in cancer cells, and progress through interactions of the cells with non-malignant tumor microenvironment. Major players microenvironment are cancer-associated fibroblasts (CAFs), which support malignancy, comprise up to 90% mass pancreatic cancer. CAFs transcriptionally rewired cells. Whether this rewiring is differentially affected different largely unknown. Here we address question dissecting stromal landscape BRCA -mutated Wild-type ductal...
Targeting translation initiation in multiple myeloma induces inhibition of a specific oncogenic program.
Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities pre-clinical cancer studies. As result, this compounds has been significantly expanded through the development efficient synthetic schemes. However, it is unknown whether all members rocaglate act similar mechanisms action. Here, we present comprehensive study comparing biological >200 rocaglates better understand how presence different...
SUMMARY By means of trapping experiments, the times activity Apodemus Glethrionomys and Microtus were studied in field mainly areas where populations had been marked. The results serve to compare observations with data already published from controlled laboratory experiments. Clethrionomys, living same habitat, showed a wellmarked nocturnal‐diurnal rhythm. In both species their twenty‐four hour cycle its peak around dusk dawn. Except that there was no two period complete inactivity at...
The molecular chaperone Hsp90, essential in all eukaryotes, plays a multifaceted role promoting survival, virulence, and drug resistance across diverse pathogenic fungal species. is also critically important, however, to the pathogen's human host, preventing use of known clinical Hsp90 inhibitors antifungal applications due concomitant host toxicity issues. With goal developing with acceptable therapeutic indices for treatment invasive infections, we initiated program design synthesize...
Candida auris is an emerging fungal pathogen that exhibits resistance to multiple drugs, including the most commonly prescribed antifungal, fluconazole. Here, we use a combinatorial screening approach identify bis-benzodioxolylindolinone (azoffluxin) synergizes with fluconazole against C. auris. Azoffluxin enhances activity through inhibition of efflux pump Cdr1, thus increasing intracellular levels. This conserved across clades, exception clade III. also inhibits in highly azole-resistant...
Exposure to anthropogenic endocrine disruptors has been listed as one of several potential causes amphibian declines in recent years. We examined gonads 814 cricket frogs (Acris crepitans) collected Illinois and deposited museum collections elucidate relationships between the decline this species spatial temporal distribution individuals with intersex gonads. Compared preorganochlorine era studied (1852-1929), percentage increased during period industrial growth initial uses polychlorinated...
Identification of novel drug targets and affordable therapeutic agents remains a high priority in the fight against chronic hepatitis C virus (HCV) infection. Here, we report that cellular proteins prohibitin 1 (PHB1) 2 (PHB2) are pan-genotypic HCV entry factors functioning at post-binding step. While predominantly found mitochondria, PHBs localize to plasma membrane hepatocytes through their transmembrane domains interact with both EGFR CRaf. Targeting PHB by rocaglamide (Roc-A), natural...
The essential eukaryotic chaperone Hsp90 regulates the form and function of diverse client proteins, many which govern thermotolerance, virulence, drug resistance in fungal species. However, use inhibitors as antifungal therapeutics has been precluded by human host toxicities suppression immune responses. We recently described resorcylate aminopyrazoles (RAPs) first class capable discriminating between (Cryptococcus neoformans, Candida albicans) isoforms biochemical assays. Here, we report...
Nanoparticle-mediated intervalence transfer was reported with ferrocene moieties that were attached onto the ruthenium nanoparticle surface by ruthenium−carbene π bonds. The resulting particles exhibited two pairs of voltammetric waves a potential spacing about 200 mV and rather intense absorption peak in near-infrared range (∼1930 nm) at mixed valence. Both features suggested Class II characteristics intraparticle mainly arose from through-bond interactions between metal centers. Quantum...
Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within medical community public at large. This is unusually resistant to antifungals, threatening overwhelm current management options. By screening a library structurally diverse molecules, we found that C. surprisingly sensitive translation inhibition by class compounds known as rocaglates (also flavaglines). Despite high level conservation across fungi in their protein synthesis machinery, these inhibited...
Macrocyclic compounds (MCs) are of high interest for inhibition challenging drug targets, but existing oral MC drugs occupy regions chemical space that not well sampled by many available synthetic chemotypes.
Abstract Use of three topical antiseptic compounds—benzalkonium chloride (BAC), benzethonium (BZT), and chloroxylenol (PCMX)—has recently increased because the phaseout other antimicrobial ingredients (such as triclosan) in soaps disinfecting sanitizing products. Further, use products general during coronavirus (COVID‐19) pandemic. We assessed environmental safety BAC, BZT, PCMX based on best available fate effects data from scientific literature privately held sources. The ecological...
Tree species composition and density were monitored in closed oak‐hickory forest forest‐prairie edge for a period of five years after prescribed burn. In the forest, tree stem declined markedly following basal area decreased from 17.5 m 2 /ha 630 trees/ha preburn sample to 12.0 310 later. contrast, on edge, increased slightly during same time 3.0 117 5.2 172 trees/ha. Our data suggest that canopy forests fire susceptible areas accumulate fuels levels encourage fires sufficient intensity...
In an effort to expand the stereochemical and structural complexity of chemical libraries used in drug discovery, Center for Chemical Methodology Library Development at Boston University has established infrastructure translate methodologies accessing diverse chemotypes into arrayed biological evaluation. a collaborative effort, NIH Genomics determined IC 50 ’s Plasmodium falciparum viability each 2,070 members CMLD-BU compound collection using quantitative high-throughput screening across...
Mercury-specific diffusive gradient in thin films (DGTs) were used laboratory microcosms as a biomonitoring tool to assess the lability of mercury (Hg) total and monomethylmercury Hg (MeHg), develop relationship between chemical bioavailability estuarine sediments. Time-series deployment DGTs sediments showed that sediment-bound MeHg is more labile than inorganic Hg. In subsequent experiments, deployed simultaneously with three benthic macroinvertebrates (the amphipod, Leptocheirus...