Natarajan Aravindan, PhD
Dr. Natarajan Aravindan is an Assistant Professor with the Department of Radiation Oncology. He completed his graduate studies in microbiology at Andhra University, India, and had postdoctoral training in radiation oncology and critical care at the UT Health Sciences Center at San Antonio and UT M.D. Anderson Cancer Center, respectively. He joined the OUHSC as a tenure-track faculty member in 2006 and has been a highly-productive investigator. His strength as a researcher is further evidenced by the number of publications he has as an independent investigator.
Project 4: Targeted Immunoliposomal EF24 Against Rel Orchestrated Neuroblastoma Relapse and Metastasis
The long-term goal of Dr. Aravindan’s research is to define the regulatory mechanisms mediated by NFkB in therapeutic intervention tumor progression and metastasis. Dr. Aravindan's laboratory has recently shown that forced inhibition of NFkB enhances IR-induced NB cell death and targeting NFkB with curcumin increases radiation therapy-induced cytotoxicity. His project, Targeted Immunoliposomal EF24 Against Rel Orchestrated Neuroblastoma Relapse and Metastasis, examines the efficacy of EF24, a synthetic analog of curcumin with enhanced cytotoxicity and improved physicochemical properties, with a neuroblastoma target using anti-GD2 targeted liposomes.
Using an NB xenograft model, Dr. Aravindan will determine: (Aim 1) whether RT could initiate PFC leading to a persistent activation of NFκB and subsequent survival advantage and initiation of clonal expansion; (Aim 2) whether IR regulated eNOS dependent NO activates MMP9 and to study its role in NFkB dependent MMP/TIMP imbalance, NB progression and metastasis; (Aim 3) the efficacy of EF24-IL=>GD2 in inhibiting IR-induced NFkB-TNFa cross signaling dependent persistent activation of NFkB mediated survival advantage and clonal expansion; and (Aim 4) the potential effect of EF24-IL=>GD2 in IR-inhibited eNOS-NO dependent MMP9 induced NFkB mediated NB progression and metastasis. On completion, this study will provide insight into the orchestration of NFκB after RT and its downstream response. Most importantly, this study could lead to the development of a “deliverable” to test in clinical settings to mitigate local failure and metastasis that could lead to a positive impact on NB patients.
Mentor: Joe Z. Zhao, PhD
Co-Mentor: Xin Zhang, MD, PhD
Anupama Munshi, PhD
Dr. Anupama Munshi accepted a tenure-track position at OUHSC in 2011. She obtained her graduate training in Molecular Biology at All India Institute of Medical Sciences, India. She completed her post-doctoral studies at Tulane University School of Medicine and UT MD Anderson Cancer Center in radiation oncology. Her postdoctoral studies were focused on identifying the molecular correlates involved in resistance to radiation therapy and identification of therapeutic methods to enhance radiosensitization. She has an excellent track record of publications in this area of research in high-impact journals such as Cancer Research, Oncogene, Clinical Cancer Research, Molecular Cancer Therapeutics, Molecular Therapy, and JBC.
Project 1: HuR: Role in Mediating Resistance to Radiation
Dr. Munshi’s long-term goal is to establish a Radiation Oncology laboratory within the Stephenson Cancer Center and the Department of Radiation Oncology that will focus on understanding molecular events that govern tumor response to radiation and other anticancer agents as well as toward developing innovative and effective approaches to sensitize tumor cells to radiation and DNA damage. Her project is based on the hypothesis that the mechanism of development of radiation resistance in human breast cancers involves a dynamic interplay between the RNA binding protein-HuR, the MAPK pathway, and DNA repair proteins.
Based on the preliminary findings, it is hypothesized that cytoplasmic HuR, through its interaction with stress activated signaling pathways and DNA repair proteins, functions to stabilize transcripts essential for cell survival and plays an important role in dictating radiation response. The project will test the hypothesis that cytoplasmic HuR interacts with the MAPK and DNA repair proteins to modulate radiation resistance. Furthermore, these studies will attempt to establish possible associations between radiation response, HuR expression, and other clinico-pathologic variables using tissue arrays and other innovative methods. Since the understanding of the different cellular mechanisms that lead to radiation resistance will have significant clinical implications, the proposed studies can identify mechanisms by which HuR contributes to radiation resistance and will define strategies for reversing the radio-resistant phenotype.
Mentor: Lawrence Rothblum, PhD
Co-Mentor: Terence Herman, MD