Cancer is fundamentally a disease that alters the programming of genes. It corrupts the normal processes that create the diversity of cells in the human body and produces cells that multiply uncontrollably and invade normal tissues.
Key drivers for cancer are oncogenes and tumor suppressor genes, both of which act as genetic on or off switches, and when mutated, can cause cancer.
Charles Lin’s research combines molecular, computational, and chemical biology approaches to study gene control in cancer. He was recruited to Baylor College of Medicine, Department of Molecular and Human Genetics, from the Dana-Farber Cancer Institute, where he was a postdoctoral fellow. A First-Time Tenure-Track Award from CPRIT in 2015 lured Lin back to Texas; he is originally from San Antonio. Lin cofounded and co-directs the Therapeutic Innovation Center at Baylor.
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Cancer is fundamentally a disease that alters the programming of genes. It corrupts the normal processes that create the diversity of cells in the human body and produces cells that multiply uncontrollably and invade normal tissues.
Key drivers for cancer are oncogenes and tumor suppressor genes, both of which act as genetic on or off switches, and when mutated, can cause cancer.
Charles Lin’s research combines molecular, computational, and chemical biology approaches to study gene control in cancer. He was recruited to Baylor College of Medicine, Department of Molecular and Human Genetics, from the Dana-Farber Cancer Institute, where he was a postdoctoral fellow. A First-Time Tenure-Track Award from CPRIT in 2015 lured Lin back to Texas; he is originally from San Antonio. Lin cofounded and co-directs the Therapeutic Innovation Center at Baylor.
Oncogenes and tumor suppressor genes commonly code for proteins called transcription factors, which read and interpret the DNA genetic blueprint. Unlike most proteins, transcription factors don’t have three-dimensional structures but are instead very dynamic, “like a wet noodle,” Lin says. So interfering with them in a typical fashion, by using a small-molecule drug to clog up an active site of an enzyme, for example, won’t work. They’ve long been thought to be “undruggable.”
Surprisingly, a certain class of drugs called “imids” actually does bind to transcription factors—but until recently, no one understood how they worked. The drug thalidomide, which has been successfully used to treat multiple myeloma, binds to a transcription factor and recruits the cell’s “garbage” machinery to cut up the protein and recycle its components.
Lin wondered if he could find other small molecules that could do the same thing. He’s testing a variety of drug candidates for their ability to bind to different transcription factors. Once he discovers some that work, he plans to engineer them to recruit the cell’s own clean-up crew to get rid of the defective proteins.
In other work, he’s studying how cancers co-opt normal developmental pathways and use them to drive unnatural development and growth of tumors. This means tumors often have remnants of that developmental lineage in them, which Lin says can point the way to finding its Achilles heel. “Tumors are made up of cells from distinct lineages, and in response to drugs they can often transition from one to another,” Lin says. “This might sound scary, that you target one lineage and just drive the cancer to morph into another. But it’s a finite number—which is what I think is really exciting. In neuroblastoma there are essentially two distinct lineages, and if you can target both of them, you can have a profound effect on the tumor.”
“Having the critical mass of researchers, clinicians, and patients at the Texas Medical Center creates the environment to move quickly.” He adds, “When you’re in the lab working on something that’s very abstract, it’s hard to know where to point your compass. I’ve strived to work at cancer centers so that my compass is always pointed in the right direction to ultimately benefit patients.”
CPRIT’s $2 million investment has resulted in more than $3.5 million in additional funding for Lin’s research since he came to Baylor. He has initiated biotech industry collaborations, received support from private foundations including the Pew Charitable Trust and the British Brain Tumour Charity, and received grants from the National Institutes of Health.
Lin earned his undergraduate degree in biology and physics from Duke University, and his Ph.D. in computational & systems biology from the Massachusetts Institute of Technology. He began a postdoctoral fellowship in medical oncology at Dana-Farber in 2012.
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