Thomas Jefferson University Hospital
Methodist Hospital Division of Thomas Jefferson University Hospital

Dr. Simone is a board-certified radiation oncologist who has a particular interest in using technological advances in radiation oncology to minimize side effects of treatment while still optimally treating the area of disease. Nicole treats a variety of malignancies but has concentrated on breast cancer for which she has conducted several clinical trials. She works closely with our multidisciplinary team of radiologists, pathologists, surgeons and medical oncologists to ensure that optimal treatment is chosen for each individual patient.

In the clinic, Dr. Simone had focused on the treatment of breast malignancies with radiation therapy and therefore her laboratory has focused on breast cancer progression and metastases and the normal tissue toxicity caused by treatment.

The laboratory has particular interest in the effect of radiation on microRNA expression. MicroRNAs (miRNA) are small, well-conserved, non-coding RNA species that regulate protein levels by interfering with translation. Their role in the cellular response to exogenous stress that induce free radicals or DNA damage, such as radiation exposure, is still being elucidated.

The laboratory has shown that alterations in miRNA expression due to ionizing radiation are also produced in response to DNA-damaging agents, oxidative stress, or both and that the response to radiation-induced stress can be reversed with the addition of a free radical scavenger. This suggests that miRNA signaling is important in all aspects of radiation-induced stress and induces a common expression signature to exogeneous genotoxic stressors, and that there may be a role for the manipulation of miRNA expression as a tool to alter the effects of radiation. As such, miRNA are logical targets for therapeutic intervention. But even more importantly, miRNA agonists and antagonists are being developed that may have a role in altering the response of both normal and malignant tissue to the effects of radiation. Further studies investigating specific miRNA responses and elaborating the mechanisms underlying these responses, verifying miRNA gene targets, and validating these findings in vivo are under way.

One such miR of interest to this laboratory is miR-21 which is a highly conserved microRNA which has been shown to be upregulated in a number of cancers including breast, pancreas, lung and glioblastoma multiforme. Our laboratory has developed in vitro and in vivo models to evaluate this microRNA in tumor progression.

The lab is also evaluating the role of caloric restriction in cancer progression. While it is understood that caloric restriction may prevent cancer, we have shown that it can be used therapeutically and acts synergistically with standard cancer therapies to cause tumor regression. We are currently evaluating the mechanism involved in this process to better understand how this may be best harnessed as a therapy.