Exploration of Intratumoral Heterogeneity with Multimodal 3D Imaging at Single-Cell Resolution to Improve Precision Medicine for Cancer

This project aims to reveal new information about intratumoral heterogeneity by examining intact human tumor samples with multimodal 3D imaging at single-cell resolution.

We will explore clinical tumor samples from patients with bladder cancer, breast cancer, and Hodgkin lymphoma and investigate: Aim-1, Novel biomarkers for precision medicine; Aim-2, Anti-PD-L1 refractory tumors; Aim-3, The cancer stem cell pool; Aim-4, Epithelial-to-mesenchymal transition; Aim-5, Platinum resistance; Aim-6, Tumor vasculature.

By examining well-established and novel markers, including non-coding RNA, with high-resolution 3D imaging, we will map the internal landscape and intratumoral heterogeneity of whole tumor samples to determine which biomarkers can be used to improve prognosis and precision medicine for cancer patients.Our group has published several papers showing that 3D imaging of cleared tumor samples can be used for detailed examinations of intact tumor samples (Trends Cancer 2018) and provide more accurate diagnoses than standard methods used in hospitals (Nature Biomed Eng 2017).

Recently we published another paper showing that multimodal 3D imaging of proteins and RNAs is a powerful tool that can reveal yet unknown details about the inner landscape of tumors, such as cell niches and cancer stem cell populations (Nature Biomed Eng 2020).

This project will use our 3D imaging platform to address various aspects of intratumoral heterogeneity to improve precision medicine for cancer.