Ping Mu, PhD

Our lab is dedicated to uncovering the molecular mechanisms that drive resistance to targeted and immune therapies in prostate and other cancers. We are also pioneering innovative therapeutic strategies to overcome these resistances, utilizing a range of state-of-the-art techniques, including 3D-cultured organoids, single-cell sequencing, and spatial transcriptomics. Our recent work has been published in top-tier journals such as Cancer Cell (2020, 2023), Cancer Discovery (2024), Nature Cancer (2022), and Oncogene (2024).

Exciting Research Directions in the Lab:

1. Mechanisms of Therapy Resistance and Tumor Evolution in Prostate Cancer

Our lab investigates the molecular mechanisms driving therapy resistance in prostate and bladder cancers, with particular emphasis on lineage plasticity, epigenetic rewiring, and mutagenesis. We aim to unravel how lineage transitions contribute to resistance and to identify novel combination strategies that can prevent or reverse these adaptive states. By leveraging CRISPR-based Perturb-seq in 3D organoid models, we systematically dissect the function of novel tumor suppressors and oncogenes and uncover resistance drivers to AR-targeted and immune therapies. These efforts are complemented by studies on tumor evolution, heterogeneity, and the mechanisms promoting genomic instability under therapeutic pressure.

2. Tumor Microenvironment, Immune Modulation, and Spatial Heterogeneity

Understanding how prostate and bladder cancers interacts with and remodels its microenvironment is central to our research. We study how tumor-intrinsic factors modulate immune evasion and reprogram stromal and immune cell populations to support resistance. To achieve spatial and single-cell resolution, we perform integrative single-cell and spatial transcriptomic profiling of clinical specimens. These analyses, coupled with advanced machine learning, allow us to construct detailed cellular atlases of prostate tumors and their microenvironments, guiding the discovery of microenvironment-informed therapeutic strategies.

3. Translational Platforms: AI-Driven Precision Medicine and Patient-Derived Organoids

Our lab develops and applies proprietary AI models tailored for prostate and bladder cancers, integrating single-cell and spatial transcriptomic data from FFPE samples and patient-derived organoids to predict molecular subtypes and therapy response. These tools power a precision oncology framework that enables data-driven treatment selection. In parallel, we generate patient-derived 3D organoids as functional avatars to test therapeutic efficacy and resistance. By combining organoid-based drug testing with AI-guided prediction, we aim to deliver individualized, evidence-based treatment strategies for prostate cancer patients.