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Research

Promising Junior Investigators

 

To enhance cancer research and infrastructure in Oklahoma, the Stephenson Cancer Center, through the COBRE Award, is intensively training its promising junior investigators. Four PJIs were selected and each has been assigned a mentor and co-mentor who are established cancer researchers in Oklahoma with expertise related to the PJI's project. 

Promising Junior Investigators include:

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

Franklin A. Hays, PhD

Dr. Franklin Hays is a tenure track Assistant Professor with the Department of Biochemistry and Molecular Biology at the OUHSC. He received his PhD in the Department of Biochemistry and Biophysics, Oregon State University, postdoctoral training at the University of California, San Francisco, and at the OUHSC. During this period, he published papers in highly respected journals including the Journal of Molecular Biology, Nature Protocols, and Science. Dr. Hays has both cell/molecular biology and structural biology expertise and thus has a creative interdisciplinary approach to his research. 

Project 2: Molecular Basis for Gemcitabine Transport in Non-Small Cell Lung Cancer Therapy 
Dr. Hays’s project analyzes a different but interrelated aspect of resistance to cancer therapy, specifically to chemotherapy. The project’s goal is to characterize, functionally and structurally, the human Equilibrative Nucleoside Transporter (hENT) involved in sensitivity and resistance to chemotherapeutic agents such as gemcitabine in lung cancer. Since resistance to gemcitabine or other nucleoside analogs could arise either from non-functional transporters with altered kinetics of gemcitabine transport, it is critical to characterize the role of hENTs in lung cancer. The results from this project are likely to provide novel insights to resistance to gemcitabine therapy and yield clues for development of strategies to overcome such resistance. His long-term goal is to fine tune chemotherapy treatment regimens for specific patient populations and tumor types in order to facilitate positive outcomes with reduced toxicity.

Mentor: Rajagopal Ramesh, PhD

Sukyung Woo, PhD

Dr. Sukyung Woo is an Assistant Professor with the Department of Pharmaceutical Sciences of the College of Pharmacy at OUHSC. She received her PhD from State University of New York at Buffalo in Pharmaceutical Sciences in 2007. Before joining the OUHSC in 2010, she had postdoctoral training at SUNY Buffalo and the Center for Cancer Research at the National Cancer Institute. Her research expertise includes pharmacokinetics, systems biology, and development of cancer therapy regimens. She has a publication record with more than twenty publications in first tier pharmacology journals as well as other high-impact journals including PLoS and Clinical Cancer Research.

Project 3: Tumor Resistance Mechanisms to Anti-VEGF Therapy in Prostate Cancer
Dr. Woo’s project aims to investigate the defective signaling mechanisms underlying resistance to VEGF-therapy in prostate cancers. In addition, her studies on stroma and tumor interactions in eliciting the resistant phenotype may provide novel insights into the role of stromal cells on tumor cell resistance and progression toward metastasis.

The main goal of this study is to elucidate potential cellular and molecular mechanisms mediating tumor resistance to anti-VEGF therapy. The main hypothesis is that induction of other proangiogenic signaling, independent of VEGF, is the leading mechanism of development of tumor resistance and is associated with hypoxia in the tumor microenvironment. Application of the innovative approaches to study this significant relationship could greatly expand our limited understanding of bypass mechanisms of tumors to anti-VEGF agents and provide rationale to select multi-targeting agents that counteract such mechanisms of resistance mediated by alternative proangiogenic signaling.

This goal will be accomplished through the following Specific Aims: 1) Identify the pathways involved in crosstalk between VEGF and VEGF-independent proangiogenic signaling transduction in stroma-tumor co-cultures; 2) Evaluate the roles of stromal cells rescuing tumors from the anti-VEGF therapy-induced hypoxia; and 3) Identify in vivo resistance signatures to anti-VEGF treatments using a xenograft model. From these experiments, Dr. Woo will identify potential pathways of resistance to be targeted, and to validate in vitro and in vivo pre-clinical models for identifying resistance to targeted agents, thereby proving insight into the design of future therapeutic strategies for tumors refractory to anti-VEGF therapy.

Mentor: Chinthalapally V. Rao, PhD
Co-Mentor: Ralf Janknecht, PhD

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