DNA damage and repair, and its impact on the genetic and epigenetic integrity of the cell in cancer and related diseases, is a key focus of research within our division. Studies are designed to improve understanding of the biological effects of radiation exposure, with the ultimate objective of providing a rational scientific basis to improve radiation therapy for cancer patients. In addition, knowledge of DNA damage and repair in normal and cancer cells will enable the development of novel therapies in cancer.

Principal investigators within DTRS are focused on areas of research ranging from the biochemical processes involved in cellular DNA damage and repair responses, to the abnormal repair pathways in cancer cells. Each of the areas of research considerably strengthen the research in its translation to the clinic and is evidenced by the translational research initiatives launched within the division. Major themes include, but are not limited to the following: 

• Understanding the molecular events underlying cancer progression, with the overall goal of delineating intrinsic differences between normal and cancer cells in order to more specifically target cancer cells and improve current cancer therapies.
• Targeting DNA repair abnormalities in cancer in combination with epigenetic therapy as a novel therapeutic strategy that is being translated into clinical trials in acute myeloid leukemia and is being developed for translation to breast, ovarian, and lung cancers in which PARP expression is abnormally increased.
• Elucidating the role of tumor microenvironments in the proliferation and adaptation of malignant tumor cells, and utilizing this knowledge to prevent or eliminate malignancy by employing various therapeutic interventions, such as radio- chemo- immuno- and thermo-therapies.

Faculty Members

France Carrier, PhD
Professor of Radiation Oncology
Director, DTRS
Associate Director of Basic Science, UMGCCC

Feyruz V. Rassool, PhD
Professor of Radiation Oncology
Co-director, Experimental Therapeutics Program
UMGCCC

Research Highlights

Dr. France Carrier's Lab

Dr. France Carrier’s laboratory is interested in understanding molecular events underlying cancer progression, and to delineate intrinsic differences between normal and cancer cells in order to more specifically target cancer cells and improve current cancer therapies. In particular, Dr. Carrier is investigating the radio-sensitizing effect of enzymes that deacetylate histones, histone deacylatylase inhibitors (HDACIs) to improve conventional and new radiotherapy treatments for glioblastomas, lymphoma, lung, melanoma and gastrointestinal cancers. Translational research led by Dr. France Carrier has contributed to the development of multiple clinical trials, including:

• • Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes
  • Phase II Trial of Low-Dose Whole Brain Radiotherapy With Concurrent Temozolomide and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma Multiforme (GCC 1224)
  • Pelvic Radiotherapy With Concurrent Neoadjuvant FOLFOX for Patients With Newly Diagnosed Rectal Adenocarcinoma (GCC 1314)

Other notable accomplishments by researchers within this group include data generated by Dr. Carrier’s group on low-dose fractionated radiation therapy (LDFRT) leading to identification of dual oxidase 2 (DUOX2), an enzyme functioning in the production of hydrogen peroxide, as a major contributor to chemopotentiation by LDFRT. DUOX2 is overexpressed in gastrointestinal cancers and could be used as a biomarker to potentially stratify these patients for clinical applications of chemopotentiation by LDFRT.

Dr. Feyruz Rassool’s Lab

Dr. Feyruz Rassool's laboratory focuses on the effects of abnormal DNA damage, repair, and immune activation in solid cancers and leukemias as a response to epigenetic therapeutic agents combined with DNA repair inhibitors (e.g. PARP inhibitors) and immune activators (e.g. STING agonists). One mechanistic focus of her work is the activation of pathogenic mimicry responses leading to STING-dependent interferon signaling and inhibition of abnormal DNA repair in honing therapeutic strategies in cancer. Notably, her team recently discovered the innate immune gene ZNFX1 as a master regulator of mitochondrial dysfunction and STING signaling in ovarian cancer. Using mouse and tumor-derived patient organoid (TDPO) models, her research is examining how these drug combinations reshape the tumor microenvironment (TME) to trigger anti-tumor immunity. Preclinical studies in her lab have been translated to Phase 1 clinical trials testing promising anticancer combinations drug therapy of epigenetic drug ASTX727 plus PARP inhibitor talazoparib in patients with acute myeloid leukemia (AML) and triple-negative or hormone resistant/HER2-negative metastatic breast cancer.

These research studies are in collaboration with Maria Baer, MD, Director of Hematologic Malignancies and Co-Leader of the Cancer Therapeutics Program at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), along with collaborators at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. The research is funded by the Van Andel Institute-Stand Up to Cancer® (SU2C) Epigenetics Dream Team.

Learn more about the Cancer Therapeutics (CT) Program at UMGCCC.