Sean Morrison, an internationally recognized leader in stem cell research, heads the Children’s Medical Research Institute, directly linking research laboratories at UT Southwestern with physicians at Children’s and Parkland Hospitals. He was recruited from the University of Michigan in 2011with the aid of a CPRIT Established Investigator Award. He studies the nexus between stem cells and cancer cells.
Stem cells are the human body’s “master” cells, or the body’s way of renewing itself after loss or damage to a tissue. Bone marrow stem cells, for example, daily restock billions of red and white blood cells and platelets in the bloodstream by dividing to form more specialized daughter cells.
In order to persist throughout life, stem cells also make more stem cells to renew and replenish themselves. Morrison and his colleagues study the cellular mechanisms that make that possible.
“One of the things we’ve learned is that cancer is a disease of dysregulated self-renewal,” Morrison said, “in which cancer cells hijack the mechanisms that stem cells normally use to replicate themselves, and inappropriately activate those mechanisms to form tumors.”
By better understanding those processes inside a cell, Morrison hopes to discover new ways to treat cancer by blocking the cell division and replication of abnormal cells, without affecting normal stem cells.
Morrison studies cancers of the blood (leukemia) and skin (melanoma). At UT Southwestern, his laboratory team discovered the microenvironment in the bone marrow where blood-forming stem cells are maintained. Knowing more about this microenvironment may eventually improve the lives of cancer patients by better regenerating this blood-forming system after chemotherapy or improving the safety of bone marrow transplants.
While studying melanoma in mice, Morrison and his team were surprised to discover that, paradoxically, antioxidants speed the spread of metastatic disease. Antioxidants—nutrients that slow oxidative damage in the body—help prevent DNA damage that leads to cancer. But Morrison found that once melanoma cells are dividing and moving throughout the body, they are actually sensitive to oxidation. More oxidants in the blood may cause the cancer cells to break down.
Clinical trials of cancer patients treated with antioxidants not only failed to stop cancer metastasis, but also actually made the disease worse. Morrison’s research now shows, at the molecular level, why this is so. “We might improve cancer therapy by treating with pro-oxidants,” he said, “rather than antioxidants.”
Morrison has filed three patent applications related to melanoma chemotherapy, including targeting this oxidative sensitivity of metastasizing melanoma. He’s also received a CPRIT grant of $900,000 to further study the cellular mechanisms that affect melanoma metastasis.
In research aimed at studying how stem cells utilize nutrients, Morrison found that Vitamin C is crucial for preventing leukemia. He found that stem cells soak up a lot more Vitamin C than other types of cells. If Vitamin C is limited, an enzyme inside stem cells fails to work properly, accelerating the cellular damage that leads to cancer. Decades of population studies have shown that people with lower Vitamin C levels in their bodies are at greater risk for cancer, and now Morrison’s work begins to explain why.
Morrison says that CPRIT has really increased the quality of the scientific research environment in Texas. Because of declining federal funding for medical research, many laboratories struggle to find enough funding just to keep going, he says.
“But in science it’s necessary to take risks, to be able to try out ideas that, if true, would transform the field,” he says. “But many scientists are playing it safe and just trying to hit singles, rather than swinging for the fences and trying to hit a home run.”
CPRIT’s initial investment in Morrison’s laboratory allowed him to expand the scope of his research into cancer far beyond what he would have been able to do in Michigan. “In Texas, with CPRIT, we have ‘risk capital,’ to take on these important problems,” he says.
Morrison received his undergraduate degree in chemistry and biology from Dalhousie University in Halifax, Nova Scotia, and his Ph.D. in immunology from Stanford University. He became a Howard Hughes Medical Institute Investigator in 2000. Dr. Morrison received the Presidential Early Career Award for Scientists and Engineers (2003), a MERIT award from the National Institute on Aging (2009) and was elected to the National Academy of Medicine (2018).
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