I am an expert in increasing the therapeutic index of radiation by understanding how patient characteristics altering metabolism. My bench to bedside and back approach allows for novel discoveries that are easily translated to the clinic. My research interest is to change the landscape of cancer care by empowering patients to use dietary interventions to improve outcomes. The overarching goal of my laboratory is to increase sensitivity of tumors with a poor response to standard therapies. To accomplish this, the lab uses diet to alter cell metabolism via signaling pathways to increase cancer cells’ vulnerability to cytotoxic therapy. Through our studies, we have found new methods for treating tumors, which has led to the development of innovative clinical trials. I am the Leader of the Cancer Risk and Control Program for the Sidney Kimmel Cancer Center and the Margaret Q. Landenberger Endowed Professor and Vice Chair of Radiation Oncology at Thomas Jefferson University. I have had considerable experience in translational research, medical treatment, education and training. I have experience taking laboratory based research to the clinic, identifying clinical observations and going back to the laboratory to investigate further. I joined the Jefferson faculty as Assistant Professor after a position as an Assistant Clinical Investigator at the National Cancer Institute. My laboratory has contributed significantly to studying regulation of microRNAs and the downstream effects of microRNAs on cell metabolism via dietary alterations. Her laboratory demonstrated for the first time that caloric restriction (CR) modifies microRNA expression (Ørom et al., Cell Cycle, 2012). The Simone laboratory then explored the physiologic impact of CR and demonstrated that CR can augment radiation therapy (Saleh et al., Cell Cycle, 2013), which she then translated directly into a clinical trial using diet during radiation for early stage breast cancer patients (NCT01819233). The lab found the same improved physiologic response of the primary tumor in vivo when CR was combined with chemotherapy, which was translated directly to a clinical trial (NCT02827370). Dr. Simone’s laboratory also investigated the role of microRNAs in the ability of CR to decrease metastatic disease burden via control of the ECM (Jin et al., Breast Cancer Res Treat, 2014; Simone et al., Cell Cycle, 2016). These findings led to her third IIT in which diet modulation prior to definitive oncologic surgery for patients with endometrial, prostate, and breast cancer will be evaluated to favorably alter expression of microRNAs as drivers of cancer progression (NCT02983279). The primary endpoint of this clinical trial is to use biomarkers to demonstrate we are able to change the systemic inflammation in our patient population by assessing their miR-21. We have matched tissue before and after diet in the breast cancer patients on this trial and will be analyzing it as part of this proposal. Finally, we have created a novel model (miR-21 knockout murine model) and have demonstrated its unique phenotype of both radiation sensitivity in vivo (Puccetti et al., IJROBP 2019) and role in cancer initiation and metastases (Dan et al., Cancers 2021). In my role as Leader of the Cancer Risk and Control program, I have placed significant effort into community outreach by educating populations at risk in our catchment area including our elderly, African American, LGBTQ and Asian American community. This effort has allowed me to be personally involved in health disparities issues and I am eager to apply the research in my laboratory to trying to narrow these disparities.