Our Science – Coleman Website
C. Norman Coleman, M.D.
Dr. Coleman's current research program is based on long-standing interest in the tumor-induced and radiation-induced stress responses. The long-term focus is on developing molecular targeted radiation therapy. An overarching concept is of radiation therapy as 'focused biology' wherein radiation is described by the molecular events produced rather than by just the dose in Gray.
Based on long-standing interest in NSAIDs and COX inhibitors, a focus of the laboratory over the last few years has been studying the effects of drugs and molecular-targeted agents at clinically relevant concentrations. Using COX inhibition as an example, we have demonstrated that the gene expression profile is very different when NSAIDs and COX2 inhibitors are used at high versus a low, clinically relevant concentration and also that siRNA is different than any of the drug conditions. This emphasizes the critical importance of using clinically relevant concentrations for preclinical mechanism and biomarker studies. That the NSAIDs induced a cardiovascular gene profile in both tumor and normal tissue (Note- this limited clinical utility of COX-2 inhibitors not discovered until post-market evaluation) suggests that it might be possible to predict normal tissue toxicity of drugs using molecular profiling, an observation being pursued.
A new program underway that began in collaboration with Dr. Jim Mitchell is that of radiation inducible molecular targets that builds on our 'focused biology' approach in which radiation can create molecular changes within the radiation field. These changes may be useful in inducing or enhancing cell killing by drugs and molecular-target agents and would be a novel therapeutic approach. This builds on both the non-oncogene addiction and synthetic lethality models and may be a unique use of radiation therapy. Our first publication on this topic included gene expression changes and further manuscripts have been accepted, under review and in preparation studying miRNA and phosho- protein changes with single and fractionated doses. In this 'nano-IMRT' concept, the radiation dose and fractionation would be selected based on molecular target activation.
Dr. Coleman's efforts in the Radiation Research Program, DCTD include the Clinical Radiation Oncology Branch (Dr. Vikram), Molecular Radiation Therapeutics Branch (Dr. Yoo) and the Radiotherapy Development Program (Dr. Bernhard). The RRP efforts in addition to the grants management and support include: and development of radiation modifiers (Dr. Yoo), cancer disparities (Dr. Wong), radiation therapy technology and quality assurance (Drs. Deye and Capala), international cancer collaborations (Dr. Vikram and Daphtary ), overall radiation research initiatives (Drs. Bernhard, Prasanna and Wong) including radiogenomics , molecular therapeutics (Drs. Bernhard, Yoo and Vikram) and the support of clinical trials through CTEP (Drs. Vikram and Deye). There is ongoing collaboration between NCI and NIAID (Dr.Maidment) to develop medical countermeasures for radiation injury (Drs. Prasanna, Wong, Vikram RRP) that could have clinical application for oncology. Dr. Coleman and Dr. Judith Bader are subject matter experts working on the civilian medical response to radiation and nuclear related incidents in the Office of the Assistant Secretary for Preparedness and Response HHS.
This page was last updated on 6/7/2013.