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Dual/Joint/Adjunct Appointment

Dennis Hughes, MD, PhD, a graduate of the MD/PhD (MSTP) Program at Yale University, is Associate Professor of Pediatrics at MD Anderson Cancer Center. He has received numerous awards as a clinician and researcher, including being named to the Best Doctors in America, America’s Top Oncologists and America’s Top Pediatricians. He is the national PI for a first-in-children phase I evaluation of panitumumab in pediatrics, and is a member of the Bone Tumor Biology Sub-committee for the Children’s Oncology Group.  As a physician-scientist, he focuses on osteosarcoma, both in the clinic and the laboratory. He is a pediatric oncologist with the Children’s Cancer Hospital at MD Anderson Cancer Center, and his clinical practice is limited to children with bone tumors such as osteosarcoma and to children with melanoma. His laboratory investigates mechanisms of metastasis and therapy resistance in osteosarcoma, focusing particularly on cell signaling and pathways that may be targets of small molecule medicines, especially the Notch and ERBB signaling pathways. Since Notch is difficult to target with inhibitory therapies, his laboratory is exploring the regulation of this pathway in sarcoma, both upstream and downstream of Notch itself, seeking better therapeutic targets.  Building on their success in these investigations in osteosarcoma, the laboratory now is evaluating these same targets in other solid tumors such as Ewing sarcoma, Neuroblastoma and GIST. In the laboratory, Dr. Hughes has supervised four graduate students, 5 postdoctoral fellows, 4 medical student researchers and 6 undergraduate researchers. He is a frequent lecturer in graduate student courses, especially the Cancer Cell Signaling Course of the GSBS, and has served on 11 graduate student advisory, examining and supervisory committees, including 5 for MD/PhD students.  He also lectures at other institutions, both about his laboratory research and about pediatric melanoma, prevention and sun safety for children and teens.

My laboratory investigates mechanisms of metastasis and therapy resistance in osteosarcoma, focusing particularly on cell signaling and pathways that may be targets of small molecule medicines, especially the Notch and ERBB signaling pathways. Within the ERBB pathway, we are evaluating the hypothesis that pan-ERBB inhibition will be more effective therapeutically for osteosarcoma than would selective inhibitors, due to redundant signaling mechanisms and unique functions of Her-4 in this disease. With the focus on Her-4, we are exploring its unique contributions to chemotherapy resistance and the specific relationship Her-4 has to anchorage-independent growth and anoikis resistance.   

We also maintain a focus on the role of notch in sarcoma. Our published work demonstrates a role for Notch pathway expression in promoting invasion and metastasis in osteosarcoma, and we currently are extending these studies to other sarcomas. Since Notch is difficult to target with inhibitory therapies, we are exploring the regulation of this pathway in sarcoma, both upstream and downstream of Notch itself, seeking better therapeutic targets. Our latest data suggests that Metadherin is essential for osteosarcoma invasion and metastasis and may be an outstanding candidate for novel therapies. Our overall goal for these studies, both with ERBB and Notch, is to identify new approaches for osteosarcoma therapy that exploit unique aspects of sarcoma biology.

Osteosarcoma, Pediatric Melanoma, Pediatric GIST, Desmoid tumor, other solid tumors of childhood.

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Last updated: 2/6/2013