Xiansi Zhao

Served as lead project manager in charge of conducting long noncoding RNA (lncRNA) let-7/Lin28 targeted drug discovery project and directing 2–3 associate scientists. Supervised and effectively facilitated training for improving laboratory skills and data analysis.

• Developed and executed low to high throughput cell-based phenotypic and functional assays with tumor cells and primary immune T cell/macrophage cells for target identification and drug discovery.
• Established and utilized mouse xenograft tumor models to describe PK/PD relationships, and in vivo proof of concept for target validation in an immuno-oncology discovery environment.
• Discovered new targets of lncRNA by applying CRISPR and next generation sequencing (NGS), validated targets in both in vitro and in vivo models with siRNA, ASO or mRNA treatment.
• Responsible for communication between functional groups and formulated data-driven decisions for program teams.
• Overcame technique difficulties and established sensitive assay that can consistently detect the change of miRNA levels (qPCR, ddPCR).
• Developed and validated immuno-oncology cell phenotypic assays, including T cells/macrophages activation, T cell-mediated chemotaxis assay, microfluidic 3D spheroid co-culture, 3D colony formation assays, immunofluorescence, and Incucyte image-based live-cell assays to identify the effect of identified target on T cell-mediated tumor cell killing.
• Negotiated with and optimized CROs to design and oversee in vivo animal experiments, handled downstream blood and tissue treatment, assays, data analysis and interpretation.

Managed and executed projects of developing antisense oligonucleotides (ASO) drug for therapy of rare genetic diseases.

• Successfully developed active ASO drugs and transferred the projects into clinical trials.
• Increased output and reduced timelines for drug development through establishing automatic high throughput platform for nucleic acid extraction and drug screening.
• Planned, executed, and analyzed biological experiments in the projects of CNS neurological diseases including schizophrenia, Amyotrophic Lateral Sclerosis (ALS) and Huntington’s Disease (HD); liver nonalcoholic steatohepatitis (NASH) disease; and muscular Duchenne muscular dystrophy (DMD) Exon splicing.
• Selected and applied iPSC-derived neurons, primary human hepatic cells, and patient-derived myoblast cells as disease-relevant in vitro models for drug screening, target validation, and pharmacology assays.
• Performed tier 1 ADME assays, in vivo PK/PD and TK assays, PBMC multiplex cytokine assays, and human primary hepatic cell CYP 450 assay to evaluate ASO candidates.
• Developed molecular/cellular assays including RT-qPCR, enzyme assays, western blot, RNAscope, reporter assays, MSD, ELISA, flow cytometry, fluorescent imaging.
• Generated stable Duchenne muscular dystrophy (DMD) Exon deletion myoblast cell line by applying CRISPR/cas9 editing technology. Operated Illumina sequencing to detect and confirm exon deletion in selected cell clones.

• Managed and operated integrated lab automation infrastructure including Echo, Bravo, Combine, and HighRes BioSolutions integrated automation system to support project-based HTS screening.
• Developed and executed high throughput cell-based phenotypic assays and biochemical-based immunoassays for oncology drug discovery and identification; for therapeutic antibody screening and functional analysis (internalization activity, ADCC/CDC activity, T cell killing-LDH).
• Built and implemented high throughput immunofluorescence (IF) high-content cell image assays to identify and validate therapeutic antibody, and to study MOA of lead compounds.
• Established and performed different types of ELISA assays (384 well plate) to screen and validate binding affinity, PK/ADA, and species cross-reactivity of therapeutic and ADC antibodies.
• Executed multicolor flow-cytometry (iQue Screener PLUS) to detect immune T cell activation, proliferation, and suspend tumor cell response to therapeutic antibody or ADC treatment.
• Developed and performed biochemical assays for signal pathway and drug discovery, including TR-FRET, HTRF, AlphaLISA assay.

• Generated DUB and UB shRNA library with molecular cloning followed by transfection and screening. USP13 was discovered and identified as a new therapeutic target for melanoma therapy.
• Characterized USP13 by mRNA deletions and point mutation strategy.
• Validated USP13 function in melanoma development through xenograft tumor model.
• Secured NIH grant and published in Nature Communications (2011).