L 陽明交大臨醫所賴峻毅老師實驗室 National Yang Ming Chiao Tung University Taipei Veterans General Hospital Comprehensive Breast Health Center
Lab group, February 2023 Lab group, June 2023 Lab outing at Junjianyan, February 2023 Lab gathering, March 2026
01 / 04 The team · Feb 2023
Jiun-I Lai Laboratory · NYCU Institute of Clinical Medicine

Cancer biology
meets precision medicine.

Our lab focuses on basic and translational cancer biology research in breast cancer and, more recently, urothelial cancer. Our previous discoveries include epigenetic mechanisms in hormone receptor-positive (HR+) breast cancer, made by incorporating novel biochemical and molecular biology techniques. Our current focus is on neoantigens and the antigen-presentation machinery in breast cancer, with the aim of developing novel immunotherapy approaches for HR+ breast cancer, a subtype traditionally thought of as an immune desert.

Neoantigen discovery and therapeutic development in hormone receptor-positive breast cancer

Hormone receptor-positive (HR+) breast cancer has long been considered immune cold, and current immunotherapies have failed to provide substantial benefit. Estrogen receptor (ER) signaling is now thought to suppress the antigen-presenting ability of cancer cells, dampening the immunogenicity of their intrinsic neoantigens. Both neoantigen properties and the antigen-presentation machinery shape this process. We are investigating the role of ESR1 in immune suppression, as well as how to boost immune recognition in HR+ breast cancer. Our ultimate goal is to develop immunotherapy approaches for this traditionally immune-cold cancer, and potentially to extend them to other immunotherapy-resistant cancer types. (See our preliminary publication: Lai et al., Transl Oncol. 2026 Sep;71:102876. doi:10.1016/j.tranon.2026.102876)

Neoantigen presentation by HLA class I to the T cell receptor, and the MHC class I antigen-processing pathway

CDK7 inhibition reverses CDK4/6 resistance through the Hippo pathway.

A small-molecule kinase screen combined with functional genomics revealed a previously unknown link between CDK7 and the Hippo pathway. We are dissecting the mechanism using BRET, structural biology, and engineered CDK6 mutants to understand how CDK7 inhibition reverses resistance in HR+ breast cancer.

Presented at AACR 2023 — poster available here →

HR+ breast cancer CDK7 Hippo / YAP-TAZ Chemical biology
CDK7 / Hippo pathway figure
Fig. 1 — pathway schematic

Mapping the CDK6 interactome to find the next escape route.

We discovered a CDK6 mutation (D224Y) that confers resistance without altering inhibitor binding — pointing to undiscovered downstream mechanisms. Using APEX2 proximity labeling and mass spectrometry, we are systematically mapping CDK6's binding partners in wild-type and mutant states.

Chung et al. identified the 14-3-3 protein YWHAB as a mediator of CDK4/6 inhibitor resistance — manuscript under revision.

CDK6 D224Y APEX2 / proximity labeling YWHAB Mass spec proteomics
Proximity labeling proteomics figure
Fig. 2 — APEX2 workflow