SUMMARY
The research of Michael D. Story, Ph.D., centers on understanding the biological effects of ionizing radiation, particularly in the context of cancer therapy and space radiation exposure. Dr. Story develops novel therapeutic strategies to treat cancer, including using charged particles — particularly carbon ions — for radiotherapy. Other novel therapeutic strategies for cancer include optimizing radiation with immunotherapy and targeted agents.
Dr. Story's laboratory also is determining the mechanism of action of tumor treating fields and using an evidence-based approach to identify combinatorial agents to target therapy-resistant tumors. Ultimately, his research integrates basic science with translational applications, aiming to improve clinical outcomes for patients with cancer.
Dr. Story has had a long-running interest in the effects of heavy charged particles on human biology. This interest has been developed by years of research for NASA on radiation-induced carcinogenesis from heavy ions such as those found in deep space and for which astronauts on missions to the moon or Mars would be exposed. He has translated this interest and knowledge gained to the use of heavy particles for cancer therapy.
With the decision by Mayo Clinic to build the first hospital-based carbon ion radiotherapy center, Dr. Story is building a center of academic excellence in charged particle radiobiology.
Focus areas
- Vulnerabilities in radioresistant tumors. Dr. Story exploits vulnerabilities seen in radioresistant tumors when irradiated by carbon ions. Heavy particles such as carbon depend on specific DNA repair pathway activation because of the complex DNA damage generated by these particles. If those pathways are known, they can be targeted as part of therapy.
- Radiation and immune therapy. Dr. Story optimizes the combination of radiation, especially heavy ions, with immune therapy. Heavy particles appear to be more immunogenic than conventional X-ray therapy. But how radiation combines with immunotherapy requires a better understanding of the timing of events in the immune response and how radiation at an inappropriate time could be detrimental to tumor response.
- Carbon ion radiotherapy. Dr. Story identifies patients who are at risk to have radioresistant tumors prior to radiotherapy so that the most appropriate radiation is applied, whether X-rays, protons, or carbon ions. Since carbon ion radiotherapy access will initially be limited, Dr. Story is developing bioindicators of radioresponse to triage patients to the right therapy.
- Tumor treating fields therapy. Dr. Story discerns the mechanism of action of tumor treating fields to develop combinatorial therapies, particularly with radiation, to enhance the efficacy of tumor treating fields therapy.
Significance to patient care
Dr. Story's research integrates basic science with translational applications to make clinical outcomes better for patients with cancer. The ultimate goal is to personalize therapy. By understanding the genetics of a tumor and, where possible, understanding the intrinsic radiosensitivity of a tumor, healthcare professionals can select the right therapy for each patient.
Heavy particles are a new tool to treat patients with cancer, particularly those who have radioresistant tumors. While the focus for now is on carbon ions, other ions may have specific properties that will benefit tumor response or spare normal tissues from harm and provide a better quality of life after radiotherapy.
Professional highlights
- Director of Radiobiology, Mayo Clinic, 2024-present.
- Member, Board of Directors, National Council on Radiation Protection and Measurement, 2019-2025.
- Vice chair, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2017-2024.
- Inaugural David A. Pistenmaa, M.D., Ph.D., Distinguished Chair in Radiation Oncology, University of Texas Southwestern, 2013-2024.
- Inaugural chair, Biology Sub-Committee of Particle Therapy Cooperative Group, 2017-2019.
- Counselor at large, Radiation Research Society, 2015-2018.
- Teaching Award, Association of Residents in Radiation Oncology, 2012, 2017.