Le Xuan (Truong) Nguyen Lab
Research Overview
A central focus of our work is defining the mitochondrial, nucleolar and transcriptional vulnerabilities that sustain leukemic stem cells and solid tumor cancer stem cells. By integrating mechanistic biology with translational models, we aim to transform fundamental discoveries into first in class therapies capable of delivering durable clinical responses.
We lead multiple drug development programs spanning small molecules, plant-derived natural products and immunotherapies. Our small molecule efforts target cancer associated PCNA to induce transcription–replication conflicts, disrupt metabolic fitness, and eliminate cancer stem cells. In parallel, our natural product program identifies bioactive plant compounds that trigger ferroptosis and apoptosis while suppressing ribogenesis in therapy resistant stem cells. Complementing these approaches, we develop immune-based strategies — including bispecific antibodies and CAR T platforms — to redirect T cells toward leukemic stem cell-enriched antigens and eradicate residual disease. Across all programs, we emphasize pharmacokinetic or pharmacodynamic integration, biomarker discovery and rational combination strategies to accelerate clinical translation.
Additionally, our laboratory investigates microRNA-based regulation of cancer metabolism and immune function, leveraging miRNA targeting platforms to simultaneously suppress malignant stemness and enhance anti tumor immunity. Collectively, our research unites systems level mechanism with therapeutic innovation, propelling small molecules, natural products, and immunotherapies from bench to bedside. Our long-term goal is to establish broadly applicable, mechanism-guided treatments that overcome therapeutic resistance and improve outcomes for patients with high-risk and refractory cancers.
Targeting Mitochondrial Metabolism in Leukemic Stem Cells
This project aims to define and therapeutically exploit mitochondrial vulnerabilities in leukemic stem cells (LSCs), the key drivers of relapse and treatment resistance in leukemia. We investigate how disrupting oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and mitochondrial dynamics (fission–fusion balance) elevates oxidative stress and selectively triggers LSC apoptosis while sparing normal hematopoietic cells. By integrating mechanistic studies with drug development and translational models, this work seeks to establish mitochondrial metabolism as an actionable therapeutic axis and advance metabolism‑targeted strategies toward clinical application for high‑risk and therapy‑resistant leukemia.
miRNA Targeting in Leukemic Stem Cells
This project examines how microRNAs regulate LSC survival and interactions with the vascular niche. We focus on key miRNAs that modulate stemness, mitochondrial metabolism, and therapy resistance while shaping the leukemic microenvironment. Through the development of miRNA‑based therapeutic approaches, our goal is to selectively eliminate LSCs and disrupt their protective niche, offering a novel strategy to prevent relapse and enhance treatment responses in leukemia.
Targeting Cancer‑Associated PCNA to Eliminate Cancer Stem Cells
This project centers on therapeutically targeting cancer‑associated PCNA (caPCNA) to disrupt core survival pathways in both leukemic and solid‑tumor stem cells. Using the first‑in‑class caPCNA inhibitor AOH1996, we investigate how caPCNA inhibition induces transcription–replication conflicts (TRCs), DNA damage, and metabolic reprogramming, ultimately driving cancer stem cell death. By coupling mechanistic studies with translational models, this work aims to establish caPCNA as a critical vulnerability in therapy‑resistant cancers and support the advancement of AOH1996 toward clinical application for durable disease control.
Immunotherapy Targeting Leukemic Stem Cells
This project develops immune‑based strategies to eradicate leukemic stem cells (LSCs) and AML blasts using bispecific antibodies and CAR‑T cell platforms. By targeting LSC‑enriched surface antigens—including IL1RAP, CD33, and CD123—we aim to redirect T cells toward therapy‑resistant leukemic populations and eliminate residual disease. Our work integrates antibody engineering, CAR design, and functional immune assays to optimize specificity and potency, with the goal of translating next‑generation immunotherapies into the clinic for durable leukemia control.
Plant Natural Products Targeting Cancer Stem Cells
This project focuses on discovering and developing plant‑derived natural products that selectively eliminate leukemic and solid‑tumor stem cells. We investigate how these bioactive compounds induce ferroptosis and apoptosis while disrupting ribogenesis and tumor immunogenicity, thereby targeting core survival pathways in therapy‑resistant cancer stem cells. By integrating mechanism‑of‑action studies with translational models, formulation optimization, and pharmacokinetic/pharmacodynamic analyses, this work aims to advance first‑in‑class natural‑product‑based therapeutics toward clinical application for durable cancer control.
Le Xuan (Truong) Nguyen is an assistant professor in Hematologic Malignancies Translational Science at City of Hope and an adjunct assistant professor at the Translational Genomics Research Institute (TGen). His laboratory focuses on understanding and therapeutically targeting cancer stem cell–driven programs that promote treatment resistance and disease relapse across both hematologic malignancies and solid tumors. His research integrates mechanistic cancer biology with drug development to advance first‑in‑class therapies toward clinical translation.
Lab Members
Our Publications
Latest Research News
Contact Information
34.1291661, -117.9725847
Duarte, CA 91010