Jessica Donington was selected from more than a dozen international applicants to receive one of LCFA’s first scientific research grants. In partnership with the International Association for the Study of Lung Cancer (IASLC), the LCFA Lung Cancer Research Grant awarded a 2-year $250,000 grant to Dr. Donington at New York University (NYU) for her research.
Dr. Donington, a native New Yorker trained at the University of Michigan and Rush Medical College in Chicago. She completed her General Surgery training at Georgetown University and was then trained in cardiothoracic surgery at the Mayo Clinic in Rochester Minnesota. After training she initially took a position in Thoracic Surgery at Stanford University, but in 2007 returned to New York to join the faculty of NYU in the Department of Cardiothoracic Surgery. At NYU she rejoined her long-time research mentor, Dr Harvey Pass, and she has been pursuing her desire to become an independent investigator in Thoracic Oncology. She currently splits her time between the Thoracic Surgery service at Bellevue Hospital and NYU’s Thoracic Oncology Laboratory, which is also located in Bellevue Hospital. She has recently completed a Masters in Clinical and Translational Research at NYU.
Dr. Jessica Donington’s research involves investigations into the role of osteopontin in non-small cell lung cancer. Osteopontin is a multifunctional protein that works as a regulator of many different processes throughout the body. Its central functions are related in cell migration and cell invasion. It plays an important role in normal processes like wound healing and inflammation, but also participates in abnormal processes such as fibrosis and malignancy. It has long been associated with malignancy, but exactly how is unclear. Dr. Donington and her team’s investigations into osteopontin in non-small cell lung cancer are two pronged. First, they are looking to see if we can use osteopontin levels in the blood as a biomarker for lung cancer, similar to what PSA or CEA are for prostate cancer and colon cancer. The work is early, but promising, with higher osteopontin levels in lung cancer patients compared to healthy volunteers or high risk smoking populations, and they have noted a decrease in levels with treatment. Their second focus of investigation is into how osteopontin affects the malignant behavior of lung cancer cells and what makes it switch from encouraging healthy cell migration to encouraging abnormal cell migration associated with cancer. Humans make three different varieties (splice variants) of osteopontin, which are very similar. In Dr. Donington and her team’s early work, they have been able to show that one of the varieties is associated with the aggressive behavior of lung cancer cells while the other two appear to be uninvolved. This means that they might be able to target the single malignant culprit and leave the other two varieties to continue their important work throughout the body.
She states that this grant comes at an “incredibly important time in my career. Without this type of foundation support specifically for young investigators in lung cancer research, the funding gap for this disease will continue, and it sustains my hopes to enable a lifelong career in lung cancer research.”
She goes on to state how grass roots organizations such as the LCFA can change the course of a disease, as has been shown in breast cancer. “First, they raised awareness and removed stigma, then they raised money to support research, which dramatically improved survival. The same can and should happen in lung cancer, and this is an important step toward increasing the nationwide research interest in this far too common and deadly malignancy.
My research focused on increasing our understanding of the potential for osteopontin as a biomarker for early stage non-small cell lung cancer and in understanding how osteopontin boosts tumor growth and spread. Osteopontin is a protein made by cancer cells which can be found in the blood and that can serve as a marker for more advanced and aggressive disease, but we don’t really know how it works. Osteopontin is also made by cells associate with healing and inflammation and is important in those processes. My work centers on figuring out how and why osteopontin is different in cancer than in these processes, and how it may be related to the specific variant that is made by cancer cells.
With the first part of my research grant, we were able to show in a small group of patients who had their cancers diagnosed as part of a CT Screening trial, that osteopontin levels in the blood rise steadily over time and that the rise in osteopontin over time was a very powerful way to help differentiate those screening patients with very early cancers from those with benign nodules. This was the first time that osteopontin has been considered as a tool to help diagnose early stage lung cancer. We are now working to validate these findings in a larger CT screening population.
In the second part of the grant we worked to determine which specific variants of osteopontin had the most impact on tumor growth and to see if we could detect that specific variant in the blood. Osteopontin has three variants which have very similar structure, differing by only a handful of amino acids. We recognized that a small 27 amino acid sequence was essential to its malignant properties in lung cancer and then went on to determine that by simply looking for the two variants of osteopontin which contain that 27 amino acid sequence we could more accurately distinguish cancers from benign nodules, suggesting that the specific variant is important in lung cancer progression.