Dr. Castellino is an Associate Professor at Emory and Children's. Dr. Castellino joined the Emory and Children’s in 2007 after completing a fellowship in pediatric hematology/oncology in 2005 and serving on the faculty from 2005 to 2007 at the Texas Children’s Cancer Center/Baylor College of Medicine in Houston, Texas.
Dr. Castellino received a bachelor’s in mechanical engineering and materials science at Duke University, and then a master’s in aeronautics and astronautics at the Massachusetts Institute of Technology prior to completion of his medical doctorate at Duke University in 1999. He subsequently completed his residency in pediatrics at Harvard Medical School/Massachusetts General Hospital in 2002. He is board certified in pediatrics and pediatric hematology/oncology.
Beginning in medical school, when Dr. Castellino determined sensitivity of brain tumor models to topoisomerase inhibitors in the laboratory of Dr. Henry Friedman, he has had a passion for understanding the pathogenesis of pediatric brain tumors and for using clues from aberrant signaling to develop novel treatments. Dr. Castellino is a physician-scientist and pediatric neuro-oncologist who treats pediatric brain tumor patients. He is also a member of the Developmental Therapeutics and Precision Medicine programs in the Aflac Cancer Center. Dr. Castellino is a member of the Cancer Cell Biology Research Program in the Winship Cancer Institute of Emory University, a National Cancer Institute (NCI)-designated Comprehensive Cancer Center. He is a member of the Neuroscience Graduate Program at Emory, and he is Co-Chair of the Emory University Research Committee.
Dr. Castellino’s translational research focuses on aberrant signaling that diverts normal developmental programs toward the growth of high-grade malignancy in the developing brain. In particular, he is interested in the pathobiology of medulloblastoma and diffuse intrinsic pontine glioma (DIPG). Medulloblastoma is the most common malignant brain tumor of childhood. Current treatments, which include surgical resection, cranio-spinal irradiation and combination chemotherapy, can cure between 60 and 70 percent of children diagnosed with this disease. Unfortunately, factors such as young age at diagnosis, incomplete surgical resection, presence of leptomeningeal dissemination and large cell/anaplastic histology have been associated with a poor prognosis for cancer survival. Even those who are cured often have long-term morbidities that adversely affect their ability to grow, think and function independently as an adult. The 30 to 40 percent of children who do not respond to initial therapy or who experience disease recurrence after treatment eventually succumb to disease.
DIPG is a clinically aggressive high-grade glioma that is localized to an area of the brain that is crucial for control of vital functions, and thus not amenable to resection. Despite recent advances, DIPG is associated with the highest mortality of all pediatric brain tumors. No chemotherapy has demonstrated efficacy against this disease. Radiation provides palliation, but almost all children succumb to disease within one to two years of diagnosis.
This highlights the urgent need for a better understanding of the molecular pathogenesis of medulloblastoma and DIPGs. Recent publications have hypothesized that medulloblastoma can be separated into four distinct subgroups based on gene expression: WNT, Sonic Hedgehog (SHH) and Groups 3 and 4. DIPGs have not been characterized as well at the molecular level. Our current research is focused on the role and targeting of p53 pathways in high-grade pediatric brain tumors. P53 has been described as the guardian of the genome because of its essential role in numerous cellular processes, such as DNA damage response and metabolism, which may ensure normal growth and development of organisms. And, p53 is one of the most frequently mutated genes in cancer. However, even in the context of wild-type p53, a growing body of literature supports the important role of p53 signaling pathways in tumorigenesis. Current projects in my laboratory are examining the p53-dependent and -independent functions of the PP2C-like protein phosphatase, PPM1D/WIP1, in pediatric brain tumors. We are studying the signaling that allows high expression of PPM1D to promote growth and dissemination of SHH, Group 3 and Group 4 medulloblastomas. We are also exploring the role of PPM1D in the pathogenesis of DIPGs.
The goal of Dr. Castellino’s laboratory is to use in vitro assays, mouse models and patient-derived tissues to improve understanding of the molecular drivers of high-grade brain tumors and their dissemination in children, to understand the signaling that confers resistance to radiation and conventional chemotherapeutic agents, and to design novel approaches to treatment that will improve both the survival and outcomes of children diagnosed with a high-grade brain tumor.
Dr. Castellino feels extremely fortunate to work at the Emory and Children’s a member of team of physicians, advanced practice providers, nurses, certified registered nurses and ancillary staff who are all devoted to the mission of not only curing childhood cancer but helping young patients and their families overcome the physical, mental, emotional and financial challenges that accompany a cancer diagnosis. Dr. Castellino feels privileged and honored to partner with the Emory and Children’s to provide excellent comprehensive care to the pediatric and adolescent community of Georgia.
In his spare time, you will find Dr. Castellino at Dynamo Swim Club, on his road bike, at local bookshops or farmers markets and spending time with his family and dog. Although Dr. Castellino grew up in Charlotte, N.C., he loves the diversity of the area and loves to call Decatur and Atlanta his home.