The Schiffman Lab studies pediatric hereditary cancer syndromes, with a special interest in genetic susceptibility to childhood cancers. The lab also investigates molecular changes in childhood cancers like Ewing sarcoma, and the germline genetic variation that gives rise to childhood tumors. All of our studies include the perspective of evolutionary (Darwinian) medicine, with a recent focus on the use of comparative oncology to identify universal drivers of cancer risk and development.
Li-Fraumeni Syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults. Cancers most often associated with this syndrome caused by TP53 gene mutations include breast cancer, osteosarcoma, and soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, leukemias, and adrenocortical carcinoma. The Schiffman Lab works closely with patients with Li-Fraumeni Syndrome to better understand their risk for developing cancer. Using different functional repair assays, we hope to design preventative strategies to one day reduce the risk of cancer development.
We also have several projects in the Schiffman Lab that involve Familial Paraganglioma and Pheochromocytoma Syndromes. These patients often have inherited mutations in genes such as SDHA, SDHB, SDHC, SDHD, and even SDHAF2. Working with other investigators at Huntsman Cancer Institute (HCI) and the University of Utah, including the Utah Population Database (UPDB), we’re exploring the functional genomics of SDHx mutations and their inheritance patterns. Patients with SDHx mutations can even present with Gastrointestinal Stromal Tumors (GIST), and other types of solid tumors. By better understanding the molecular causes of this rare cancer syndrome, we can start to think about novel screening and prevention strategies.
Other studies of the Schiffman Lab focus on exploring the genetic risk factors for Ewing sarcoma, a cancerous tumor that occurs in bones or soft tissues; it occurs most frequently in children and young adults. In the lab, we are investigating genetic connections in the DNA of patients with Ewing sarcoma and the risk of developing the disease. The lab team also studies the function of genes that may be downstream targets of EWS-FLI, the chromosomal translocation associated with Ewing sarcoma, using copy number analysis of genes of interest in tumor cell lines and patient samples. Dr. Schiffman is the principal investigator of Project GenESis, an international and NIH-funded study to identify genetic factors that contribute to the development of Ewing sarcoma.
The Schiffman Lab is also involved in many whole-exome sequencing studies, including the Utah Genome Project (UGP) which is exploring the genetic risk of families with increased childhood cancers. Working together with population scientists, bioinformaticians, and molecular biologists, the Schiffman Lab will take targets identified in the UGP to better understand their functional significance. This may lead to new therapeutic approaches for childhood and familial cancer.
Another project looks at cancer resistance in elephants. Despite their huge size, which for most mammals results in an increased risk of cancer, elephants do not get cancer (a phenomenon known as Peto’s Paradox). The Schiffman Lab has a close collaboration with the Hogle Zoo in Salt Lake City, Utah, where we are trying to identify the functional mechanism that prevents cancer in elephants. Once discovered, we will search for therapeutic cancer drugs that can mimic these effects and start clinical trials in high-risk patient populations, such as those families with Li-Fraumeni Syndrome.
Finally, working closely with investigators from around the country (including Dr. Matthew Breen at North Carolina State University), we are comparing the cancers that develop normally in dogs with cancers that develop in humans. By looking at genes in common in the cancers of humans and dogs, we’re able to narrow down the genomic drivers (the genes causing cancer) from the passengers (the genes just along for the ride, but not causing much problem). These candidate genes are then analyzed in functional and bioinformatics studies to understand their therapeutic potential. Of note, we never give cancer to dogs, only study it once it already has developed. Using this comparative oncology approach, we hope to impact the prevention and treatment of cancer in both dogs and humans.
The Schiffman Lab offers a dynamic approach to translational genomics. Working with collaborators from all over the country, and the world, we’re able to study people, dogs, and elephants. This transdisciplinary approach continues to yield new and exciting results. It is our goal to understand who gets cancer and why, and to do so in as creative and effective way as possible.