David Wong Lab

Liquid Biopsy Detection of Non-Small-Cell Lung Carcinoma: Liquid biopsy has found its way into the cancer lexicon as a reference to tumor biomarkers within blood or other readily accessible biospecimens such as saliva that reflect the presence and biology of cancer. This project interleaves the expertise of lung cancer biologists, clinicians, and biostatisticians with industry engineers, converging on a novel liquid biopsy technology "EFIRM-Liquid biopsy (eLB)" that has already shown high sensitivity detecting circulating DNA mutations in patients with EGFR-mutant lung cancers. To address early lung cancer detection we are developing and validating independent assay for circulating tumor DNA (ctDNA) and microRNA in mutations commonly observed in lung cancer. This integrated platform will be validated in patients with screen- or incidentally- detected lung nodules in the size ranges that are most diagnostically challenging. Our overall research proposition is that blood-based biomarkers using the eLB-Lung Cancer Detection Panel (eLB-LCDP) will inform the accurate and robust classification of nodules as benign or malignant. Additionally, we are examining the unique physical characteristics of ctDNA in plasma and saliva and using state-of-the-art techqniues and methods.

Supporting Grants: U01 CA233370 (EFIRM-Liquid Biopsy (eLB): Ultrasensitive ctDNA and miRNA Detection for Early Assessment of Lung Cancer), UH2/UH3 CA206126 (Advancing EFIRM-Liquid Biopsy (eLB) to a CLIA-Certified Laboratory Developed Test (eLB-LDT) for Detection of Actionable EGFR Mutations in NSCLC Patients, and 1R21CA239052 (Ultra-short circulating tumor DNA (uctDNA) for liquid biopsy of non-small cell lung cancer).

Salivary Gastric Extracellular RNA Biomarkers for Gastric Cancer Detection: Extracellular RNA (exRNA) is an emerging paradigm as endocrine signals in cellular communication, biomarker development, therapeutic applications and systemic physiology. Our laboratory first reported the existence of a transcriptome and microRNA profile in  cell free saliva followed by its scientific characterizations and clinical utilities including biomarker development for molecular oncology applications. Most recently we have performed RNA-sequencing in cell free saliva and reported three major types of RNA in saliva (mRNA, miRNA and snoRNA). We are interesting in testing the hypothesis that salivary extracellular RNA (exRNA) can be developed for the clinical detection of human diseases using gastric cancer as a model disease.  Additionally we seek to improve and optimize current methods for salivary-exosome isolation which have been shown to be the vesicular transporter that houses exRNA cargo.

Supporting Grants: 1UG3/UH3 TR002978 (Acoustofluidic Separation (AFS), Purification and Raman Spectral Fingerprinting of Single EVs: From Cell of Origin to Target Cell and Biofluids), UH2/UH3 TR000923 (Clinical Utility of Salivary Extracellular RNA Biomarkers for Gastric Cancer Detection), and Ronnie James Dio “Stand UP and Shout” Cancer fund.

Assessing piRNAs in Oral Wound Healing: The objective of this project is to identify epigenetic alterations associated with accelerated oral wound healing phenotype in human oral keratinocytes. Using next-generation bisulfite sequencing, differential transcriptomic analysis, and bioinformatics analysis, we aim to identify the mechanism of oral specific   piwi-interacting RNA (oral-piRNAs) in oral keratinocytes. BLAST results demonstrated oral-piRNAs mapping to transposable elements, specifically Alu. Knockdown of oral-piRNAs resulted in altered Alu methylation. Current findings suggest oral-piRNAs as intrinsic factors that modulate molecular pathways in human oral keratinocytes through de novo methylation of Alu elements.

Supporting Grants: F30 DE027615 (Oral-piRNAs Enhance Re-epithelialization in Oral Wound Healing).