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Physics and Biology in Medicine Graduate Program

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Molecular and Cellular Oncology Specialization


Goal

The goal of this track is to prepare students for careers as independent investigators in all fields concerned with the biological effects of radiation. This includes radiobiological careers as Ph.D. researchers in university departments, in clinical radiation oncology practices, in biotechnology industries,and with private and governmental bodies concerned with environmental issues. This track is supported by both the Division of Molecular and Cellular Oncology (DMCO - in the Department of Radiation Oncology) as well as the Center for Medical Countermeasures against Radiation (CMCR).

Faculty and students in this track perform research in the areas of:

DMCO Research areas:

  • Proteasomes: Proteasome is a direct redox-sensitive target for radiation; even very low doses can slow the rate of protein degradation, including that of critically important signaling molecules. Investigations are being carried out into proteasome inhibition using drugs as a useful means of causing radiosensitization in vitro and in vivo.
  • Stem Cells: We have demonstrated the radiation resistance of breast cancer stem cells. An intensive area of research in the lab focuses on the relative radioresistance in the intrinsic radiosensitivity of stem cells in normal and tumorous tissues, which is likely a cause of normal tissue and tumor regeneration after radiation exposure.
  • Growth factor and cytokine signaling: These pathways influence the response of normal tissues and tumors to irradiation (the process of being exposed to radiation). We have shown that TNFR signaling dictates the response of normal brain to irradiation. In addition, we have a large research effort in the control of these pathways through SOCS proteins, and how their expression modulates radiation responses.
  • Immunity and Radiation: The intercellular "danger" response to radiation would be expected to activate antigen presenting cells resulting in the development of immune responses. In fact, we believe that radiation is a poor signal for this response and indeed switches off antigen presentation by dendritic cells without killing them. We are involved in attempts to prevent this functional immunosuppression and so as to better translate tumor cell killing into the generation of tumor-specific immunity. This would help improve local tumor control and eliminate micrometastatic disease.

CMCR Research areas:

  • Novel mitigators of radiation damage discovered through High Throughput Screening (HTS) techniques using yeast and mouse models, assessesing DNA deletions that affect both radiation induced cytotoxicity and genomic instability.
  • Modulation of radiation-induced deficits in mouse immunohematopoietic system;
  • Models of radiation effects in human lymphoid systems, including radiation-sensitive individuals.


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