The Pediatric Cancer Research Group (PCRG) and CHRI celebrate two new National Institutes of Health grants awarded to our members for research into childhood medulloblastoma (MB).
R01 Award to Coulter and Mahato
The National Institute of Neurological Disorders and Stroke awarded a research project grant (R01) to a UNMC team led by two CHRI members: Ram Mahato, PhD, professor of Pharmaceutical Sciences, and Don Coulter, MD, associate professor of Pediatric Hematology/Oncology. This five-year project, titled “Overcoming Resistance Mechanisms in Hedgehog and Myc-amplified Medulloblastoma,” began Dec. 1.
Drugs that inhibit the Hedgehog (Hh) signaling pathway are used to treat children with a specific form of medulloblastoma (MB), but repeated use quickly leads to drug resistance mutations. The UNMC team will use in vitro systems and mouse models to explore the efficacy of a dual-drug combination therapy that acts upon three different signaling molecules in cancer cells (BRD4, PI3K, and SHH).
An innovative goal of UNMC’s study is to deliver the two drugs to the brain together on nanoparticles. Dr. Coulter explained, “We hope that by targeting these specific proteins within the cancer cells we can impact the way those cells are able to grow and divide. And the package that the compounds are in is also important. These specific compounds would have trouble penetrating the blood-brain barrier on their own, so by packaging them in a nanoparticle, it will not only allow them to cross the barrier, but also direct them toward the tumor cells.”
Dr. Coulter remarked that the team is excited about the possibility that this strategy could have multiple applications in pediatric oncology. “These proteins are most likely important to a number of different types of cancers. By testing this drug delivery system in MB, we may also be able to apply the same technology to other cancers in the future. The use of nanoparticles may make a number of compounds more efficacious in different tumors.”
K12 Award to Mahapatra
Sidharth Mahapatra, MD, PhD, assistant professor of Pediatric Critical Care Medicine, has been awarded a K12 career development grant through the Pediatric Critical Care and Trauma Scientist Development Program (PCCTSDP). PCCTSDP is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The program exists to increase the number of highly trained, successfully funded, and sustainable pediatric critical care and pediatric trauma physician-scientists.
Dr. Mahapatra’s successful submission included components of research training and a research project proposal entitled, “Exploring the Chemosensitization Properties of the Novel Tumor Suppressor Gene miR-1253 in Group 3 Medulloblastoma.” As a PCCTSDP Scholar, beginning Jan. 1, Dr. Mahapatra will receive structured mentorship and over $200,000 in funding for salary support, research operating costs and travel to the program’s annual retreats. During the award period, Dr. Mahapatra will develop a proposal for longer-range NIH research funding.
Working across specialties is one of Dr. Mahapatra’s trademarks. In his words, “My research niche is unique in that it derives from two different sub-specialties, pediatric critical care medicine and pediatric neuro-oncology. I have yet to encounter this type of specialization in the PCCM world.” One of his hopes as a PCCTSDP Scholar is to “heighten awareness into this type of inter-disciplinary research project to encourage others in my field to pursue what they feel most passionately about instead of trying to fit their research into a mold.”
“My K12 award has already led to an invitation to present my research at the Pediatric Neurocritical Care Research Group, a first step in establishing myself in this field. Now, I am finally feeling a sense of belonging with those who share similar interests.”
Dr. Mahapatra anticipates that the program will help shape his career as a pediatric intensivist and a leader in translational research. “Over a two-year award period and a total five-year mentoring period, candidates are guided through the process of developing their research to a competitive level for procurement of independent research status. Having attended several retreats, I am simply awed and humbled by how high the caliber of research is. It has given me an insider’s look into how invested the National Advisory Committee is and the success of the candidates enrolled in the program. I have always felt well supported by my mentors and collaborators at UNMC – the infrastructure, protected time, and institutional funding have helped my research gain traction. Now I have national mentorship and funding to give me the edge I need to reach the next level.”
Elevating Pediatric Cancer Research at UNMC and Children’s
According to Dr. Coulter, competing successfully for these two federal grants helps fulfill the mission of PCRG. “Clinicians have a certain way at looking at problems that can be different from the way a PhD investigator evaluates the same issue. We felt that by providing a pathway to allow these two different schools of thought to work together and identify possible solutions, we have the ability to develop projects that will eventually be successful in achieving extramural funding.”
“This has been the ultimate goal of the PCRG since its inception, and these successes reflect all the hard work completed by all the members of the team since 2014.”
by Matthew Sandbulte | January 19, 2021