Dr. Heather J. Wright, a postdoctoral research fellow in the Hingorani Lab at Fred Hutchinson Cancer Research Center, has received a prestigious three-year training fellowship from the National Institutes of Health to study the mechanisms of pancreatic cancer spread, or metastasis, to distant organs.
The NIH established the Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship, otherwise known as an F32 award, to help shepherd postdocs into independent research careers. According to the National Bureau of Economic Research, postdocs who receive this award are significantly more likely than non-awardees to go on to receive an R01, or Research Project Grant, the original and historically oldest grant mechanism offered by the NIH to help early-career scientists establish tenure-track research careers.
“Receiving this grant is an exciting step in my scientific career,” said Wright, who joined the Hingorani Lab in 2017. “It means that I have independent funding to work on a project I am excited about with a lot of translational potential, which was my goal as a postdoc. It is also an important step in my progression and transition to an independent research position.”
The Hingorani Lab focuses on pancreatic adenocarcinoma, or PDA, which accounts for more than 80 percent of all pancreatic cancer cases and has the highest mortality of any cancer. A defining characteristic of this malignancy is the unique fibrous barrier the tumor builds around itself. This barrier prevents small molecules, such as those used in chemotherapy, from entering the tumor. This extracellular matrix, largely made of a molecule called hyaluronan, not only acts as a physical barrier to treatment but also promotes tumor growth and metastasis.
Wright and colleagues study how hyaluronan acts through various biological mechanisms to promote metastasis. In preliminary studies using a preclinical model of human PDA, the Hingorani Lab has seen “a striking reduction” in metastasis by simply depleting the tumor’s hyaluronan supply, Wright said.
Ultimately, Wright aims to develop combination therapies that incorporate chemotherapy with targeted surgical removal of hyaluronan for pancreatic cancer patients to reduce their risk of tumor metastasis and improve their chances of survival. “To defeat an enemy, you need to learn its weaknesses and it seems like we can utilize PDA’s dependency on [hyaluronan] to its detriment.”
Hyaluronan is perhaps best known in dermatology circles as hyaluronic acid, or HA — an ingredient commonly used in face lotions, as it retains water and efficiently hydrates the skin. It is also naturally produced by the body to lubricate the joints.
Wright is quick to point out that hyaluronic acid itself is not carcinogenic.
“I am primarily studying high-molecular-weight hyaluronan, which, incidentally, is what protects the naked mole rat from ever getting cancer. They are one of the only animals we know of that doesn’t get cancer,” Wright said. “It’s just that pancreas cancer is really good at hijacking hyaluronan’s good intentions and kind of turning it against its human host.”
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