The Chan Lab at UT Southwestern is developing a gene therapy to reverse that betrayal — and stop metastatic breast cancer before it starts.
Caroline is my granddaughter — and she is doing work that I believe deserves far more visibility than it gets. She's a Research Assistant at the Chan Lab at UT Southwestern Medical Center, and what she's working on sits at the precise intersection of everything I find most compelling: biology, technology, systems thinking, and the fundamental question of how life works. When I learned the details of her research, I realized it was one of the most important things I'd encountered in years. I wanted to share it here, in plain language, for anyone willing to pay attention.
This page is my attempt to explain genuinely extraordinary science to a general audience. None of this is hype. The Chan Lab's discoveries are published, peer-reviewed, and internationally recognized. What follows is the real story.
Your body is equipped with a type of immune cell called a Natural Killer (NK) cell. Their job, as the name suggests, is to hunt down and destroy dangerous cells — including cancer. They're particularly effective against the invasive cancer cells that try to break away from a tumor and spread through the body.
For decades, researchers assumed that cancer simply hid from NK cells — slipping past immune surveillance through camouflage. Dr. Chan's lab discovered something far more disturbing, and far more interesting.
Cancer doesn't just hide from NK cells. It actively reprograms them — stripping away their killing ability and redirecting them to assist the tumor's spread. Your own immune system's soldiers are turned into collaborators.
— Chan et al., Journal of Cell Biology, 2020
The mechanism involves specific molecular switches. When NK cells are exposed to tumor cells, two inhibitory receptors — KLRG1 and TIGIT — become overexpressed, effectively locking the NK cells into a dormant, tumor-promoting state. The cancer has essentially changed the lock on the door.
The critical finding that followed: this corruption is reversible. Blocking KLRG1 or TIGIT, or using epigenetic drugs that inhibit DNA methyltransferases (DNMT inhibitors), restored NK cell killing ability in lab models. The door can be unlocked again.
Understanding a disease mechanism is one thing. Proving a therapy works against it in human tissue is another. That's where Caroline's work comes in.
Caroline is building patient-derived human tissue models — called organoids — from cheek swab samples, engineering them to recreate specific disease states, and then testing the lab's gene therapy drug against those models. It is painstaking, precise, and foundational to the entire drug development pipeline.
The organoid approach is essential for a specific reason: when cancer cells are grown in flat, two-dimensional lab dishes, NK cells kill them effectively. But in 3D tissue — which is what actually exists in the human body — cancer cells can overcome NK cell cytotoxicity over time. The 3D organoid model recreates this reality, making it a far more accurate and predictive testing environment than conventional methods.
The Chan Lab hasn't stopped at basic discovery. They've already translated this NK cell biology into a practical clinical tool — demonstrating the lab's commitment to research that reaches patients, not just journals.
By analyzing 236,363 cells from 119 breast tumor samples across eight datasets — the largest single-cell RNA sequencing analysis of breast cancer to date — the lab identified 10 distinct categories of breast cancer cells (vs. the 3 categories clinicians typically use). By mapping how these cancer cell subtypes interact with NK cells and other immune cells, they built a tool called InteractPrint that can accurately predict which patients will respond to immunotherapy — before they even begin treatment.
This is precision medicine in practice: instead of treating all HR+ breast cancer patients the same way, InteractPrint points toward which patients are likely to benefit from which therapies — potentially sparing others from treatments that won't work while directing effective ones to those who need them most.
Immunotherapy has been one of cancer medicine's great success stories over the past decade. But most immunotherapy targets T cells — a different arm of the immune system. Standard checkpoint inhibitors like PD-1 blockers have limited efficacy in breast cancer, and critically, they do not address the NK cell corruption problem the Chan Lab has identified. A therapy that restores NK cell function would be treating something that current drugs completely miss.
The Chan Lab accepts donations directly, with 100% going toward research to end metastatic cancer. Every contribution is tax-deductible.
When donating, select "Other" for Designation and enter Isaac Chan Research