A5005057288- Bacteriophages and microbial interactions
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Bacterial Genetics and Biotechnology
- Micro and Nano Robotics
- Lipid Membrane Structure and Behavior
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Cancer-related gene regulation
- Microfluidic and Bio-sensing Technologies
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Rare Diseases
- Peptidase Inhibition and Analysis
- Diffusion and Search Dynamics
- Machine Learning in Bioinformatics
Northeastern University
2017-2025
Boston Children's Hospital
2020-2025
Boston Children's Museum
2020-2025
Imperial College London
2022
Boston University
2019
Brown University
2013-2016
Providence College
2014
Harvard University
2014
Durham University
2013
Duke Medical Center
2000
HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during replication. However, host factors that trigger uncoating remain unidentified. Recent studies show infectious cores enter nucleus uncoat near site of integration. Here, we efficient nuclear requires synthesis a double-stranded DNA (dsDNA) >3.5 kb efficiency correlates with size. Core disruption by capsid inhibitors releases DNA, some integrates. most is degraded, indicating intact core...
We resolve the 3D trajectory and orientation of individual cells for extended times, using a digital tracking technique combined with reconstructions. have used this to study motility uniflagellated bacterium Caulobacter crescentus found that each cell displays two distinct modes motility, depending on sense rotation flagellar motor. In forward mode, when flagellum pushes cell, body is tilted respect direction motion, it precesses, tracing out helical trajectory. reverse pulls precession...
The SARS-CoV-2 nucleocapsid (N) protein performs several functions including binding, compacting, and packaging the ∼30 kb viral genome into particle. N consists of two ordered domains, with terminal domain (NTD) primarily associated RNA binding C (CTD) dimerization/oligomerization, three intrinsically disordered regions, an N-arm, a C-tail, linker that connects NTD CTD. We utilize optical tweezers system to isolate long single-stranded nucleic acid substrate measure directly function at...
Abstract Single-stranded nucleic acid (ssNA) binding proteins must both stably protect ssNA transiently exposed during replication and other NA transactions, also rapidly reorganize dissociate to allow further processing. How these seemingly opposing functions can coexist has been recently elucidated by optical tweezers (OT) experiments that isolate manipulate single long molecules measure conformation in real time. The effective length of an substrate held at fixed tension is altered upon...
ABSTRACT Genes involved in the regulation of chromatin structure are frequently disrupted cancer, contributing to an aberrant transcriptome and phenotypic plasticity. Yet, therapeutics targeting mutant forms chromatin-modifying enzymes have yielded only modest clinical utility, underscoring difficulty epigenomic underpinnings gene regulatory networks. Here, we sought identify novel epigenetic vulnerabilities diffuse large B-cell lymphoma (DLBCL). Through screens biochemical analysis,...
Chloroquine has been used as a potent antimalarial, anticancer drug, and prophylactic. While chloroquine is known to interact with DNA, the details of DNA–ligand interactions have remained unclear. Here we characterize chloroquine–double-stranded DNA binding four complementary approaches, including optical tweezers, atomic force microscopy, duplex melting measurements, isothermal titration calorimetry. We show that intercalates into double stranded (dsDNA) KD ~ 200 µM, this entropically...
Abstract Background. Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated safety, tolerability, efficacy combination capecitabine, oxaliplatin, bevacizumab in treatment metastatic esophagogastric adenocarcinomas. Methods. Thirty-seven patients or unresectable gastric/gastroesophageal junction tumors were enrolled treated capecitabine 850 mg/m2 BID on days 1–14,...
APOBEC3G (A3G) is a human enzyme that inhibits immunodeficiency virus type 1 (HIV-1) infectivity, in the absence of viral infectivity factor Vif, through deoxycytidine deamination and deamination-independent mechanism. A3G converts from fast to slow binding state oligomerization, which suggests large oligomers could block HIV-1 reverse transcriptase-mediated DNA synthesis, thereby inhibiting replication. However, it unclear how small number molecules found form oligomers. Here we measure...
Abstract Escherichia coli SSB (EcSSB) is a model single-stranded DNA (ssDNA) binding protein critical in genome maintenance. EcSSB forms homotetramers that wrap ssDNA multiple conformations to facilitate replication and repair. Here we measure the wrapping of many proteins single long substrate held at fixed tensions. We show binds biphasic manner, where initial events are followed by unwrapping as ssDNA-bound density passes saturation high free concentration increases fraction EcSSBs...
The HIV-1 nucleocapsid protein (NC) is a multi-functional necessary for viral replication. Recent studies have demonstrated reverse transcription occurs inside the fully intact capsid and that timing of uncoating are correlated. How nearly 10 kbp DNA genome stably contained within narrow with diameter similar to persistence length double-stranded (ds) DNA, role NC in this process, not well understood. In study, we use optical tweezers, fluorescence imaging, atomic force microscopy observe...
Abstract Bacteriophage T4 gene 32 protein (gp32) is a model single-stranded DNA (ssDNA) binding protein, essential for replication. gp32 forms cooperative filaments on ssDNA through interprotein interactions between its core and N-terminus. However, detailed understanding of filament structure organization remains incomplete, particularly longer, biologically-relevant lengths. Moreover, it unclear how these tightly-bound dissociate from during complementary strand synthesis. We use optical...
Bacteriophage T4 gene 32 protein (gp32) is a single-stranded DNA (ssDNA) binding essential for replication. gp32 forms stable filaments on ssDNA through cooperative interactions between its core and N-terminal domain. gp32's C-terminal domain (CTD) believed to primarily help coordinate replication via direct with constituents of the replisome. However, exact mechanisms these are not known, it unclear how tightly-bound readily displaced from as required genomic processing. Here, we utilized...