A5102890614- HIV Research and Treatment
- Evolution and Genetic Dynamics
- HIV/AIDS drug development and treatment
- Bacteriophages and microbial interactions
- Evolutionary Game Theory and Cooperation
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- Hydrocarbon exploration and reservoir analysis
- Hepatitis C virus research
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- Mast cells and histamine
- Remote Sensing and Land Use
- Advanced Measurement and Detection Methods
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Liquid Crystal Research Advancements
- vaccines and immunoinformatics approaches
- Coccidia and coccidiosis research
- RNA modifications and cancer
- Advanced Electron Microscopy Techniques and Applications
- Helminth infection and control
Westlake University
2025
EarthTech International (United States)
2025
University of California, Los Angeles
2008-2025
APLA Health
2024
Southeast University
2023
University Health Network
2020
Princess Margaret Cancer Centre
2020
Ontario Institute for Cancer Research
2018-2019
University of Toronto
2018
Zhejiang University
2014-2017
Optical imaging of nanoscale objects, whether it is based on scattering or fluorescence, a challenging task due to reduced detection signal-to-noise ratio and contrast at subwavelength dimensions. Here, we report field-portable fluorescence microscopy platform installed smart phone for individual nanoparticles as well viruses using lightweight compact opto-mechanical attachment the existing camera module cell phone. This hand-held fluorescent device utilizes (i) 450 nm laser diode that...
X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, large number families mapping to remained unresolved suggesting that more XLID or loci are yet be Here, we investigated 405 with XLID. We employed massively parallel sequencing all exons index males. The majority these males were previously tested negative for copy variations mutations subset known by...
The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on were confined to either the neighborhood around wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph only two amino acids at each site. In reality, dimensionality sequence space higher (20L) there may be higher-order interactions among more than sites. Here we experimentally characterized landscape four sites in GB1,...
We report the recording and reconstruction of x-ray diffraction patterns from single, unstained viruses, for first time. By separating pattern virus particles that their surroundings, we performed quantitative high-contrast imaging a single virion. The structure viral capsid inside virion was visualized. This work opens door broad range specimens protein machineries viruses to cellular organelles. Moreover, our experiment is directly transferable use free electron lasers, represents an...
HIV-1 persists as a global health challenge due to its ability establish latent reservoirs that evade eradication by antiretroviral therapy (ART). This study introduces high-diversity barcoded library combined with novel peptide barcode system enable single-cell multi-dimensional analysis of viral integration, transcription, splicing, and translation distinct mRNA isoform. Our method revealed over 80 splicing isoforms uncovered significant temporal variation in diversity, driven integration...
Autosomal-inherited progressive external ophthalmoplegia (PEO) is an adult-onset disease characterized by the accumulation of multiple mitochondrial DNA (mtDNA) deletions in post-mitotic tissues. Mutations six different genes have been described to cause autosomal dominant form disease, but only mutations polymerase gamma gene are known recessive PEO (arPEO), leaving genetic background arPEO mostly unknown. Here we used whole-exome sequencing and identified compound heterozygous mutations,...
Abstract RAS-MAPK signaling mediates processes critical to normal development including cell proliferation, survival, and differentiation. Germline mutation of genes lead the Noonan-spectrum syndromes. Here, we present a patient affected by 6p-interstitial microdeletion with unknown underlying molecular etiology. Examination cases reveals shared clinical features consistent disorders short stature, facial dysmorphia cardiovascular abnormalities. We find RAS-responsive element binding...
The HIV-1 pandemic is not the result of a static pathogen but large genetically diverse and dynamic viral population. virus characterized by highly mutable genome rendering efforts to design universal vaccine significant challenge drives emergence drug resistant variants upon antiviral pressure. Gaining comprehensive understanding mutational tolerance each genomic position therefore critical importance. Here we combine high-density mutagenesis with power next-generation sequencing gauge...
Drug-resistant mutations often have deleterious impacts on replication fitness, posing a fitness cost that can only be overcome by compensatory mutations. However, the role of in evolution drug resistance has been overlooked clinical studies or vitro selection experiments, as these observations capture outcome selection. In this study, we systematically profile landscape resistance-associated sites HIV-1 protease using deep mutational scanning. We construct mutant library covering...
Abstract The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays latently cells. This study utilizes barcoded analyze humanized mice. Using bulk PCR and deep sequencing methodologies, we retrieve 890 viral RNA barcodes 504 linked 15,305 integration sites at single...
HIV latency prevents cure of infection with antiretroviral therapy (ART) alone. One strategy for eliminating latently infected cells involves the induction viral protein expression via latency-reversing agents (LRAs), allowing killing host by cytopathic effects or immune effector mechanisms. Here, we combine a barcoded approach and humanized mouse model to study designed, synthetic kinase C modulating LRA on rebound. We show that administration this compound during ART results in delay...
ABSTRACT Certain “protective” major histocompatibility complex class I (MHC-I) alleles, such as B*57 and B*27, are associated with long-term control of HIV-1 in vivo mediated by the CD8 + cytotoxic-T-lymphocyte (CTL) response. However, mechanism superior protection is not fully understood. Here we combined high-throughput fitness profiling mutations Gag, silico prediction MHC-peptide binding affinity, analysis intraperson virus evolution to systematically compare differences respect CTL...
Abstract Cancer is a disease of the genome, but dramatic inter-patient variability in mutation number poorly understood. Tumours same type can differ by orders magnitude their rate. To understand potential drivers and consequences underlying heterogeneity rate across tumours, we evaluated both local global measures density: single-stranded double-stranded DNA breaks 2,460 tumours 38 cancer types. We find that SCNAs thousands genes are associated with elevated rates point-mutations, while...
Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this difficult to elucidate in vivo. Here we provide controlled assessments fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented two protective (B*57 B*27) one non-protective (A*02) MHC-I types. Libraries saturation mutagenesis CTL propagated without selective pressure define...
Abstract The structure of fitness landscapes is critical for understanding adaptive protein evolution (e.g. antimicrobial resistance, affinity maturation, etc.). Due to limited throughput in measurements, previous empirical studies on were confined either the neighborhood around wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph only two amino acids at each site. In reality, however, dimensionality sequence space higher (20 L , being length...
We present VGA, an accurate method for viral quasispecies assembly from ultra-deep sequencing data. The proposed consists of a high-fidelity protocol and assembly, referred to as Viral Genome Assembler (VGA). is able eliminate errors by using individual barcodes attached the fragments. Results on both synthetic real datasets show that our accurately assemble HIV detect rare previously undetectable due errors. VGA outperforms state-of-the-art methods assembly. Furthermore, first which scales...
Acute HIV-1 infection is characterized by the rapid generation of highly diverse genetic variants to adapt new host environment. Understanding dynamics viral variation at this stage critical for vaccine design efforts and early drug treatment. Here, using a high-resolution deep sequencing approach targeting gag region, we reveal very immune pressure with dramatic subpopulation shifts in single acutely infected participant providing further insight into acute infection.
Abstract Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. The exclusion of T cells from the tumor presence a dysfunctional compartment within microenvironment (TME) constitute two central hallmarks ICI NSCLC. Seminal studies have identified that loss LKB1 KRAS-mutant NSCLC drives ICI, potentially by suppressing STING, thereby leading dysregulation...
Abstract As a result of high rate mutations and recombination events, an RNA-virus exists as heterogeneous “swarm” mutant variants. The long read length offered by single-molecule sequencing technologies allows each variant to be sequenced in single pass. However, error limits the ability reconstruct viral population composed rare, related In this paper, we present 2SNV, method able tolerate error-rate protocol 2SNV uses linkage between nucleotide variations efficiently distinguish them from...
Abstract Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes effective treatment via combination therapies. Yet rapid evolution and high diversity HCV populations, combined with the reality suboptimal adherence, make drug resistance a clinical public health concern. We develop general model incorporating viral dynamics pharmacokinetics/pharmacodynamics to assess how adherence affects development outcomes. derive design principles adaptive...
Abstract The aryl hydrocarbon receptor (AHR) mediates many of the toxic effects 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). However, AHR alone is insufficient to explain widely different outcomes among organisms. Attempts identify unknown factor(s) have been confounded by genetic variability model Here, we evaluated three transgenic mouse lines, each expressing a rat isoform (rWT, DEL, and INS), as well C57BL/6 DBA/2 mice. We supplement these with whole-genome sequencing transcriptomic...