A5042607595- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Single-cell and spatial transcriptomics
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- RNA regulation and disease
- HIV, Drug Use, Sexual Risk
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Pneumocystis jirovecii pneumonia detection and treatment
- Innovation and Socioeconomic Development
- HIV/AIDS Research and Interventions
- RNA Research and Splicing
- CAR-T cell therapy research
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
University of Massachusetts Chan Medical School
2023-2024
University of California, San Diego
2020-2024
La Jolla Bioengineering Institute
2023
Abstract Guide RNAs offer programmability for CRISPR-Cas9 genome editing but also add challenges delivery. Chemical modification, which has been key to the success of oligonucleotide therapeutics, can enhance stability, distribution, cellular uptake, and safety nucleic acids. Previously, we engineered heavily fully modified SpyCas9 crRNA tracrRNA, showed enhanced stability retained activity when delivered cultured cells in form ribonucleoprotein complex. In this study, report that a short,...
Abstract Cell-cycle control is accomplished by cyclin-dependent kinases (CDKs), motivating extensive research into CDK targeting small-molecule drugs as cancer therapeutics. Here we use combinatorial CRISPR/Cas9 perturbations to uncover an network of functional interdependencies among CDKs and related factors, identifying 43 synthetic-lethal 12 synergistic interactions. We dissect using single-cell RNAseq, for which develop a novel computational framework precisely quantify cell-cycle...
Adherence to medication and retention in care are key contributors the efficacy of pre-exposure prophylaxis (PrEP) for prevention HIV. Therefore, it is important understand factors that may impact various settings prescribe PrEP.We evaluated associated with 3 12 months after PrEP initiation at a primary HIV clinic San Diego. Retention was defined as having an office/virtual visit within 1 month from 3- or 12-months time point interacting leading being refilled.A total 199 patients were...
Abstract Understanding the consequences of single amino acid substitutions in cancer driver genes remains an unmet need. Perturb-seq provides a tool to investigate effects individual mutations on cellular programs. Here we deploy SEUSS, like approach, generate and assay at physical interfaces RUNX1 Runt domain. We measured impact 115 RNA profiles myelogenous leukemia cells used categorize into three functionally distinct groups: wild-type (WT)-like, loss-of-function (LOF)-like hypomorphic....
Abstract CRISPR-Cas genome editing tools enable precise, RNA-guided modification of genomes within living cells. The most clinically advanced editors are Cas9 nucleases, but many nuclease technologies provide only limited control over outcomes. Adenine base (ABEs) and cytosine (CBEs) precise efficient nucleotide conversions A:T-to-G:C C:G-to-T:A pairs, respectively. Therapeutic use (BEs) provides an avenue to correct approximately 30% human pathogenic variants. Nonetheless, factors such as...
Abstract Adenosine deaminases acting on RNA (ADARs) impact diverse cellular processes and pathological conditions, but their functions in early cell-fate specification remain less understood. To gain insights here, we began by charting time-course editing profiles human organs from fetal to adult stages. Next, utilized hPSC differentiation experimentally probe ADARs, harnessing brain organoids as neural specific, teratomas pan-tissue developmental models. We show that time-series faithfully...
Single-gene missense mutations remain challenging to interpret. Here, we deploy scalable functional screening by sequencing (SEUSS), a Perturb-seq method, generate at protein interfaces of RUNX1 and quantify their effect on activities downstream cellular programs. We evaluate single-cell RNA profiles 115 in myelogenous leukemia cells categorize them into three functionally distinct groups, wild-type (WT)-like, loss-of-function (LoF)-like, hypomorphic, that validate orthogonal assays....
Guide RNAs offer programmability for CRISPR-Cas9 genome editing but also add challenges delivery. Chemical modification, which has been key to the success of oligonucleotide therapeutics, can enhance stability, distribution, cellular uptake, and safety nucleic acids. Previously, we engineered heavily fully modified SpyCas9 crRNA tracrRNA, showed enhanced stability retained activity when delivered cultured cells in form ribonucleoprotein complex. In this study, report that a short, stabilized...
Abstract Understanding the consequences of single amino acid substitutions in cancer driver genes remains an unmet need. High-throughput mutagenesis is emerging as a powerful tool to probe varying different across length protein or domain, however it currently limited specific functional readouts such target abundance assays. Studying effects genetic perturbations on cellular programs and fitness has been challenging using traditional pooled screens. Over last few years, there surge interest...
Understanding the consequences of single amino acid substitutions in cancer driver genes remains an unmet need. Perturb-seq provides a tool to investigate effects individual mutations on cellular programs. Here we deploy SEUSS, like approach, generate and assay at physical interfaces RUNX1 Runt domain. We measured impact 115 RNA profiles myelogenous leukemia cells used categorize into three functionally distinct groups: wild-type (WT)-like, loss-of-function (LOF)-like hypomorphic. Notably,...