Two recent state awards to Children’s Hospital researchers show the incredible breadth of research being conducted at The Children’s Hospital of Philadelphia Research Institute every day. Supported by the Pennsylvania Department of Health’s Commonwealth Universal Research Enhancement program, Struan Grant, Phd, will lead an investigation of the genetic links between type 2 diabetes and cancer, while Jennifer F. Culhane, PhD, will study developmental-behavioral screening instruments in children.
Established in 2001, the Commonwealth Universal Research Enhancement (CURE) program awards grants to biomedical, clinical, and health services research projects. Through 2011, the program supported 1,672 research and infrastructure projects with a total of $698 million in grants, according to the CURE website.
Last year, CHOP’s Stephen Grupp, MD, PhD, testified before the Pennsylvania State Senate on behalf of CURE after the program’s funding was threatened. Dr. Grupp, whose work received CURE support, in March 2013 published a study showing a two leukemia patients achieved complete responses after receiving T cells engineered to selectively kill cancerous cells.
“These cells don’t come from an insurance company, and they don’t come from a drug company. They come from research dollars,” Dr. Grupp said.
While the CURE funding ultimately avoided being cut last year, Pennsylvania recently announced that due to a sharp reduction in the amount of money it was due to receive through the Tobacco Master Settlement Agreement — which resolved healthcare lawsuits brought by 46 states against tobacco companies — the state would be forced to reduce funds for a number of programs, including CURE. However, Drs. Culhane and Grant’s projects will continue to be supported.
Projects Span the Research Spectrum
Dr. Culhane, an associate professor of Pediatrics at Children’s Hospital and the University of Pennsylvania, will lead a comparison of the screening instrument the Survey of Wellbeing of Young Children (SWYC). Recently developed by Tufts Medical Center’s Ellen C. Perrin, MD, and R. Christopher Sheldrick, PhD, the SWYC is a “freely-available, comprehensive screening instrument for children under 5 years of age,” according to the SWYC website.
Because the SWYC is “brand new” and is still being researched, with her project Dr. Culhane will be running a validation study of the survey to determine its applicability in underserved populations. Dr. Culhane and her team plan to compare the SWYC to previously validated instruments, she said.
The SWYC is comprised of three different “domains,” which together can give a comprehensive overview of a child’s development. Questionnaires related to behavior, development (including an autism screening), and questions related to family are included. That the SWYC is “free and short” could help it become an important screening tool, Dr. Culhane pointed out.
While the Tufts researchers have been focused on “more typical populations” in their validation studies, Dr. Culhane’s study will examine “very unique populations” of children of Spanish-speaking women — many of whom may be undocumented — and children of black women born in Africa who have immigrated to the United States. She and her colleagues, including Children’s Hospital’s Marsha Gerdes, PhD, who produced a Spanish translation of the SWYC, are already recruiting study participants, and hope to evaluate approximately 1000 patients.
Dr. Grant’s project, meanwhile, will examine the genetic commonalities of type 2 diabetes and cancer. In particular, Dr. Grant, who is a faculty member in the department of genetics at CHOP, will investigate the function of key genes that come in both disease settings, in particular TCF7L2, which is the gene most strongly associated with type 2 diabetes. Dr. Grant discovered the association between type 2 diabetes and TCF7L2 in 2006, and “thus far, it is the most strongly associated gene in type 2 diabetes reported to date,” Dr. Grant said.
But researchers do not yet fully understand the role TCF7L2 plays in causing type 2 diabetes. Moreover, TCF7L2 has also been implicated in the pathogenesis of certain types of cancer. For example, Dr. Grant pointed out, “if you get a different flavor of mutation in this gene, you’ll get colorectal cancer. So this gene is clearly both a colorectal cancer gene and a type 2 diabetes gene,” Dr. Grant said.
And follow up studies of genome-wide association study findings have revealed a key relationship between TCF7L2 and multiple forms of cancer. “So TCF7L2 is not only the top story in type 2 diabetes, it seems to be also explaining the top story in multiple cancer settings,” Dr. Grant noted.
Supported by the CURE funding, Dr. Grant hopes to “understand why there is a specific common genetic etiology to type 2 diabetes and cancer, primarily prostate and colorectal cancer.” Dr. Grant has been working with a number of CHOP and Penn faculty on the project, including Center for Childhood Cancer Research investigators Adam Resnick, PhD and Andrei Thomas-Tikhonenko, PhD, as well as Penn geneticist Klaus H. Kaestner, PhD, and Penn diabetes researcher Morris J. Birnbaum, MD, PhD.
To learn more about the CURE program, see the Pennsylvania Department of Health site.