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As Director of Pediatric Xenograft Modeling at Lurie Children’s Stanley Manne Children’s Research Institute, Xiao-Nan Li, MD, PhD, is committed to developing more precise and effective treatments to combat pediatric cancer. Dr. Li and his team create animal tumor models that parallel the unique attributes of human tumors in a process called patient-derived orthotopic xenograft modeling or PDOX modeling. These clinically relevant and molecularly accurate models are making it possible to more fully understand tumor biology, discover new markers for diagnosis, identify molecular targets of therapy, and establish preclinical therapeutic efficacy for the initiation of clinical trials of new treatment.
Dr. Li and his team use the latest technology to advance cancer research. The new Echo Liquid Handling technology and Access Laboratory Workstation are powerful tools that will support high-throughput drug discovery. They will allow the team to test nearly 11,000 approved anti-cancer drugs as well as new compounds in different combinations. A robotic arm will move droplets of candidate drugs, in miniscule amounts, from storage tubes into wells on assay plates, preventing the risk of cross contamination from human contact. Tumor cells will be added to the wells, and the robot will monitor for promising drug responses. Because the technology will work 24 hours a day, seven days a week, Dr. Li hopes to be able to screen thousands of drug combinations. Those that show the greatest success will be rapidly advanced for additional studies in his PDOX models. Ultimately, his goal is to translate the most promising therapies into future clinical trials for children.
Dr. Li’s initial work focused on brain tumors, and while he remains focused on that important work, his team is now extending their studies to other pediatric cancers such as leukemia and solid tumors. Tumor tissues will be collected both from surgical samples and from late/terminal phase tumors through autopsy. This is possible thanks to strong collaborations with the Lurie Children’s Precision Medicine Initiative and other investigators across the globe. Dr. Li’s lab is actively expanding the cohorts of their special strain of immune-deficient animals through breeding and have implanted 695 mice with various types of pediatric cancers, including 17 tumors directly obtained from childhood patients into 180 mice.
Dr. Li was recently awarded a $3.1 million U01 grant from the National Institutes of Health (NIH) to advance his brain tumor studies using mouse models. This is the second U01 multi-institutional grant that Dr. Li has received, making our hospital one of the very few in the U.S. with two major multi-million-dollar UO1 grants.