My research interests are in developing novel biomarkers and therapeutic strategies in thoracic cancers (malignant mesothelioma, thymic epithelial tumors, non-small cell lung carcinoma, etc.). These clinical objectives are achieved by integrating a better understanding of tumor biology with testing of new experimental anti-cancer agents.
Malignant Pleural Mesothelioma (MPM)
Project I – Oncogenesis Modeling
The precise molecular steps leading to MPM remain obscure and, in part, underlie why this recalcitrant surface tumor is difficult to diagnose and treat. Our goal is to construct next-generation model(s) of MPM that can provide insights on tumor initiation, promotion and progression. We developed a novel method to generate new mesothelial cells, those which give rise to MPM, directly from patient tissue biopsy of pleural membranes. Utilizing 3D bioprinting, we incorporate these genetically defined mesothelial cells into building artificial human pleural membranes arranged in a multi-well, high-throughput pipeline. This ex-vivo equivalent of human pleura represents a novel and robust experimentation platform to conduct cell-based, real-time analyses into the origin and mechanism of MPM.
Project II – miRNA-based Therapy
A major clinical bottleneck in MPM therapy is lack of efficacious, specific drugs that can be effectively delivered to the pleura space where this cancer is sheathed over vital organs. Since traditional chemotherapeutics and numerous small-molecule targeted drugs have yet to appreciably impact outcomes in MPM management, we are focused on identifying and testing novel agents. Currently we are investigating microRNA, short non-coding RNA, that are a class of epigenetic regulators interacting with transcription factors, as a promising type of cancer drug. miRNA exert anti-cancer effects by coherent simultaneous targeting of gene pathways, many of which are pathogenic in MPM and contain “undruggable” transcription factors like p53 or KRAS. We (in collaboration with the Chemical Biology Lab, NCI-Frederick) have innovated a thin-film, biodegradable, nano-scale, peptide hydrogel composite material as a locoregional delivery system (patent pending) that can deliver miRNA payloads more selectively to cancer cells. Using both unbiased high-throughput functional screens of miRNA and knowledge-based bioinformatic analysis, we are developing candidate therapeutic miRNA, e.g. miR-215 which targets p53 to induce apoptosis when applied to MPM xenografts. In addition to locoregional miRNA therapy for MPM as a monoagent, we are exploring novel combinatorial regimens with multiple classes of new drugs. Ultimately, we seek to complete preclinical studies in order to conduct future human trials assessing the clinical utility of miRNA with anti-MPM effects.
Dr. Hoang received his medical degree from the University of Minnesota Medical School, where he stayed to complete clinical training in general surgery. During his surgical residency his research work was supported by the Ruth L. Kirschstein National Research Service Award and a Training Program Grant in the Division of Hematology-Oncology. Afterwards, Dr. Hoang completed his cardiothoracic residency at the University of Pennsylvania, with an emphasis on thoracic surgery. Since 2008, he then served on faculty at Stanford University School of Medicine as an Assistant Professor. He was the Medical (co-)Director of the Stanford Cancer Center Tissue Bank. Dr. Hoang also established an independent thoracic oncology laboratory there investigating the metabolic derangements in lung cancer and microRNA interactions in mesothelioma.
- Xu Y, Zheng M, Merritt RE, Shrager JB, Wakelee HA, Kratzke RA, Hoang CD. miR-1 induces growth arrest and apoptosis in malignant mesothelioma. Chest. 2013;144(5):1632-1643.
- Zheng Y, de la Cruz CC, Sayles LC, Alleyne-Chin C, Vaka D, Knaak TD, Bigos M, Xu Y, Hoang CD, Shrager JB, Fehling HJ, French D, Forrest W, Jiang Z, Carano RA, Barck KH, Jackson EL, Sweet-Cordero EA. A rare population of CD24(+)ITGB4(+)Notch(hi) cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal. Cancer Cell. 2013;24(1):59-74.
- Chen R, Khatri P, Mazur PK, Polin M, Zheng Y, Vaka D, Hoang CD, Shrager J, Xu Y, Vicent S, Butte AJ, Sweet-Cordero EA. A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma. Cancer Res. 2014;74(10):2892-902.
- Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453-7.
Related Scientific Focus Areas
Biomedical Engineering and Biophysics
Molecular Biology and Biochemistry
This page was last updated on Monday, June 13, 2022