He Research

The goal of our research lab is to identify novel mechanisms underlying acquired resistance in cancer cells to chemotherapies and targeted-therapies with a focus on reciprocal interaction between tumor stroma cells and cancer cells.  We examine the molecular and genetic alterations in tumor microenvironment cells in response to treatment pressure during the early stage of therapy, prior to the development of irreversible resistance phenotypes caused by secondary mutations, activation of bypass pathways, and other mechanisms. We utilize advanced approaches to discover druggable targets including 3D spheroid culture, patient-derived xenograft (PDX) model, patient-derived organoid (PTO) model, gene knockout mice, sc-RNAseq, metabolomics, and mass spectrometry etc. 

We are currently investigating whether alterations of cancer-associated fibroblasts with TKIs treatment facilitate the expansion of drug tolerant persister cells (DTPs) for the development of TKI resistance. 

Arsenic and chromium (VI) are established carcinogens for lung cancer. However, environmental and occupational exposure to arsenic and chromium remains a major public health concern. By utilizing in vitro heavy-metal-transformed cell models, mice models, and population-based cross sectional studies, we have revealed that heavy-metal-induced epigenetic alterations contribute to arsenic or chromium-induced metabolic shift, angiogenesis, malignant transformation, and tumor growth. Our ongoing projects aim to characterize key molecular alterations that drive lung carcinogenesis using genetic mice models chronically exposed to Cr (VI) through drinking water or inhalation. 

Our latest work shows that neutralizing ROS in ovarian cancer cells greatly elevates exosomal miR-155-5p levels, leading to a reduction of macrophage migration and tumor spheroid infiltration, using 3D models and syngeneic mice models (J Exp Clin Cancer Res. 2022). The data provide a rationale for enhancing anti-tumor immune responses based on optimization of miR-155-5p levels. We are currently investigating the underlying mechanism by which miR-155-5p regulates stromal cells to inhibit ovarian cancer development. miRNAs are promising therapeutic approaches for cancer treatment. However, the application of microRNAs in humans is hindered by a lack of approaches to achieve high efficiency and safety concern for in vivo delivery of microRNA mimic or antimiR inhibitor. In this project, we will develop protocols for the scalable production of purified bovine milk exosomes and then load the miR-155 mimic into the exosomes for in vivo delivery. We will evaluate the toxicity and efficacy using preclinical animal models. 

We will investigate the role and mechanisms of amino acid transporters in chemo- and radio- resistance in triple negative breast cancer.