Thirumala-Devi Kanneganti, Ph.D., vice chair of the St. Jude Children’s Research Hospital Department of Immunology, has received a National Cancer Institute Outstanding Investigator Award to build on her discoveries related to the innate immune system, inflammation, and cell death in health and disease, particularly in colorectal cancer.
The prestigious award was created in 2014 to give proven cancer researchers seven years of funding to advance cancer research in the laboratory or the clinic.
“Having stable funding for an extended period allows us to pursue research questions that may be deemed too risky with a shorter funding window,” said Kanneganti, who holds the Rose Marie Thomas Endowed Chair at St. Jude.
“There is growing recognition that the innate immune system and inflammatory cell death can affect all aspects of cancer, from tumor initiation to growth and metastasis,” Kanneganti said. “Colorectal cancer is the second most common cause of U.S. cancer deaths, and innate immunity is a major player in the colon; thus, understanding how innate immune pathways contribute to the various stages of tumor development will be key to improving cancer treatment strategies.”
Funding stability also helps support training of the next generation of scientists, who are essential to ensuring strong research progress will continue, said Kanneganti, who joined St. Jude in 2007. Cancer researchers are nominated for the award by their institutions. Candidates must have served as principal investigators on NCI grants for the last five years and have demonstrated outstanding cancer research productivity.
“The NCI Outstanding Investigator Award addresses a problem that many cancer researchers experience: finding a balance between focusing on their science while ensuring that they will have funds to continue their research in the future,” said Dinah Singer, Ph.D., NCI deputy director. “With an anticipated seven years of uninterrupted funding, NCI is supporting the opportunity for investigators to fully develop exceptional and ambitious cancer research programs.”
Kanneganti is a pioneer in the NLRP3 inflammasome field, establishing the importance of NLRP3 in infectious diseases, intestinal inflammation, metabolic disease and cancer. In her studies to characterize NLRP3 inflammasome activation, her lab showed for the first time that ZBP1 is an innate sensor that drives NLRP3 inflammasome activation and inflammatory cell death, pyroptosis, apoptosis and necroptosis.
This finding, combined with her lab’s studies on the extensive crosstalk and intricate coregulation between cell death pathways that had previously been thought to be independent, led her to establish the fundamental concept of PANoptosis. The model defines a unique inflammatory programmed cell death regulated by the PANoptosome complex. The complex facilitates interactions between the machinery required for the inflammasome/pyroptosis, apoptosis and necroptosis.
In addition to cell death, PANoptosis is also associated with the secretion of cytokines that trigger inflammation and the release of other factors that alert immune cells of imminent danger. Aberrant innate immune signaling and inflammatory cell death are associated with the pathogenesis of several inflammatory and metabolic diseases, neurodegeneration and cancer.
Kanneganti and her team proposed to study the ZBP1 PANoptosome and identify other novel innate immune regulators of inflammatory cell death (PANoptosis) and their role in colorectal cancer and beyond.