CROCE AND BYRD RECEIVE NCI ‘OUTSTANDING INVESTIGATOR AWARDS’
The National Cancer Institute (NCI) has issued a pair of Outstanding Investigator Awards (R35) to help two of the most prominent cancer researchers at The Ohio State University further their groundbreaking work in cancer genetics and leukemia therapy.
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| Croce |
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| Byrd |
The prestigious multimillion-dollar awards, which provide long-term support for experienced investigators with outstanding records of productivity who propose to conduct exceptional research, will go to Carlo Croce, MD, and John C. Byrd, MD.
Croce, a Distinguished University Professor who chairs the Department of Molecular Virology, Immunology and Medical Genetics at Ohio State, will receive $924,000 annually for seven years, or nearly $6.5 million overall, for “Cancer Gene Discovery to Identify Targetable Targets.” Croce also directs the human cancer genetics program and holds the John W. Wolfe Chair in Human Cancer Genetics at Ohio State. In addition, he is a member of Ohio State’s Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James).
Byrd, a professor and director of the Division of Hematology at Ohio State, will receive $911,328 annually for seven years, or nearly $6.4 million, for “Targeted Therapy for Leukemia.” Byrd also holds the D. Warren Brown Designated Chair in Leukemia Research at Ohio State and co-leads the Leukemia Research Program at the OSUCCC – James.
Croce and Byrd are the first two investigators at Ohio State to receive an R35 award while employed by the university. Croce received two Outstanding Investigator Awards while working at another institution before he came to Ohio State in 2004.
The NCI’s website states that these awards provide extended funding stability that allows investigators “to take greater risks, be more adventurous in their lines of inquiry, or take the time to develop new techniques. The research projects should break new ground or extend previous discoveries toward new directions or applications that may lead to a breakthrough that will advance biomedical, behavioral or clinical cancer research.”
Croce’s grant will enable him and his lab team to continue their work in identifying genetic and genomic alterations that cause human cancer in order to develop targeted treatments for biologically different tumors.
Croce is one of the most cited scientists in the world, having published more than 1,000 articles in peer-reviewed scientific journals. During his long career, he has made many important discoveries in cancer genetics and has identified and characterized many cancer genes. A few of the notable contributions listed in his grant application abstract include:
• Demonstrating the juxtaposition of the MYC oncogene to the immunoglobulin loci and its dysregulation in Burkitt lymphoma, the first demonstration of specific gene alterations in human cancer;
• Discovering that chronic lymphocytic leukemia (CLL) is caused by the loss of two microRNA genes on chromosomes 13q14, miR-15a and miR-16-1. This showed that genes encoding non-coding RNAs can also be involved in cancer pathogenesis, shattering the previous belief that only protein-coding genes that represent only 2 percent of the human genome were important and that the remaining 98 percent constituted “junk” DNA;
• Discovering that tumors such as lung and pancreatic cancer secrete microvesicles that fuse with macrophages and dendritic cells, starting a process that facilitates tumor spread and metastatic disease.
Byrd’s grant will enable him and his lab colleagues to integrate targeted therapy with immune therapy to produce curative therapies for patients with CLL, the most common form of adult leukemia and a disease that is currently incurable.
His grant application abstract explains that his lab focuses on basic and translational biologic questions to develop immunologic and targeted therapies for various hematologic malignancies. His team uses CLL as a disease model because it allows integration of mechanistic and genetic studies in leukemia mouse models with studies using primary tumor samples, thus enhancing the clinical relevance of their findings.
“I envision the greatest impact from my research will come from integrating therapeutics that target tumor survival pathways with agents that reverse immune tolerance to facilitate long-term remissions or cure,” Byrd writes, noting that his work to date has resulted in FDA approval of two agents for CLL therapy that prolong survival.
He states that his team’s work with the drug ibrutinib “dispels a commonly held paradigm that it is not possible to develop a general disease-targeted therapy when a specific genetic aberration is not present. My hypothesis is that general disease-targeted therapy requires a dual tumor-targeted and immunologic modulation.” Byrd intends to develop this concept and extend it to other blood cancers as well.
