Jianjun Gao

My laboratory conducts translational research that leverages clinical biospecimens and data to investigate the mechanisms of response, resistance, and toxicity to immunotherapy, targeted therapy, and chemotherapy in patients with genitourinary malignancies, particularly bladder and kidney cancers. We validate our findings using in vivo models to develop novel preclinical therapeutics with enhanced efficacy and reduced toxicity, ultimately aiming to translate these insights into clinical trials. We employ a range of cutting-edge technologies, including single-cell RNA sequencing, single-cell metabolomics, spatial transcriptomics, spatial proteomics, peptide microarray-based diagnostics, serum-based, AI-driven platform for neoantigen discovery, and in vivo CRISPR screening, etc. to interrogate clinical samples and somatic mouse models that genomically represent genitourinary cancers. Our major areas of research interest include: 1. **Mechanisms of resistance to immunotherapy**, including tumor-intrinsic genomic alterations (e.g., defects in interferon signaling, chromosome 9p21 loss, DNA methylation) and tumor microenvironmental changes (e.g., VISTA overexpression on macrophages). 2. **Determinants of clinical response to immunotherapy**, such as the presence of tumor-associated tertiary lymphoid structures, RNA splicing error-induced neoantigen generation, and endogenous retrovirus induction. 3. **Mechanisms of immune-related toxicities**, with a focus on autoimmune antibody-mediated syndromes such as pneumonitis, colitis, and dermatitis. 4. **Mechanisms of response and resistance to targeted therapies**, including FGFR3 inhibitors in bladder cancer. 5. **Identification of dual-action tumor neoantigens**—those capable of activating both T and B cells—using a personalized, high-throughput, serum-based, AI-driven platform, with applications in vaccine development, cancer diagnostics, therapeutic efficacy monitoring, immune toxicity management, and cellular therapy. 6. **Mechanistic studies of cancer metastasis**, with particular emphasis on lung, bone, and brain metastases.