Cancer Biology program members conduct research to discover biochemical, metabolic, and genetic abnormalities in tumor cells and nonmalignant cells in the tumor microenvironment and exploit these findings to develop more effective ways to prevent, diagnose, and treat cancer. Most members’ research focuses on breast, pancreas, lung, and prostate cancers, which are particularly relevant to patients in our local communities.
- Discover novel oncogenic signaling cascades that promote cancer development and progression. Determine basic biological processes that promote cancer development and progression, focusing on cell signaling. This aim brings together investigators conducting basic, translational, and clinical research to discover the unique signaling events that contribute to cancer development and progression. Cancer Biology members have formed collaborative and integrated groups investigating signaling cascades driven by small GTPases and kinases, because these signaling pathways provide a rich source of therapeutic targets to suppress cancer initiation and progression.
- Conduct cutting edge research in mitochondrial and redox biology. Define how abnormalities in energy metabolism and free radical generation promote cancer, with the goal of developing effective therapies to target the unique metabolic and energetic signatures of cancer cells. Cancer Biology members have made seminal discoveries in free radical metabolism and the chemical biology of superoxide, nitric oxide (NO), and peroxynitrite. They use state-of-the-art techniques involving electron paramagnetic resonance (EPR) spin trapping, fluorescence detection of reactive oxygen species (ROS) and NO, and measurements of mitochondrial bioenergetics. Ongoing efforts include linking cancer metabolism & energetics with cell signaling to define mechanistic associations between mitochondrial respiration, ROS and oxidative metabolism, activation of AMPK and Stat transcription factors, and tumor growth and metastasis.
Selected NIH Funded Projects, Cancer Biology Program
Michael Flister, PhD | Genetic Mapping of Breast Cancer Risk in the Tumor Microenvironment
Approximately 30% of breast cancer risk is inherited, yet the majority of genetic risk factors remain unknown. Of the known genetic risks, most are thought to directly affect the malignant cancer cell and have been linked to aggressive disease, reduced response to chemotherapy, shorter times between relapse and shorter survival. What is less known are germline variants - gene changes in a reproductive cell (egg or sperm) that become incorporated into the DNA of every cell in the body – that might impact breast cancer risk through the tumor microenvironment. The tumor microenvironment consists of the nonmalignant cells that impact many aspects of breast cancer, including tumor formation, progression, and response to therapy. In this study, we develop and utilize a novel tool (Consomic Xenograft Model) for understanding the germline genetic modifiers that impact breast cancer outcome through the tumor microenvironment, which we hope will lead to the discovery of new therapeutic targets for better diagnosis and treatment of breast cancer.
Peter LaViolette, PhD | Brain Cancer Radio-Pathomics for Predicting Heterogeneous Cytology
This project will give a complete picture of the microcellular features underlying brain tumor imaging to individualize diagnoses and treatments for patients with deadly brain glioblastomas. This information will dramatically improve care and clinical decision-making for patients and clinicians. By examining whole brain human samples and clinical MRI scans Dr. LaViolette can provide a detailed understanding of how brain tumors, at the cellular level, appear on macroscopic imaging. Eventually, the need for human tissue in this study will be eliminated through the development of computational algorithms created using knowledge of microscopic cell structure to recognize patterns in MRI scans (radio-pathomics).
Jong-In Park, PhD | Mechanisms of MEK/ERK Growth Arrest Signaling
This grant continues Dr. Park’s research into the MEK/ERK pathway which is frequently deregulated in cancer. This makes the pathway a key target for new cancer therapies, including a promising strategy to use this pathway to exploit natural weaknesses of cancer cells associated with aberrant MEK/ERK activity.
Ling Wang, MD, PhD | Regulation of Tumor Cell ANGPTL4 by Astrocyte-Secreted TGF-Beta2 in Triple-Negative Breast Cancer Brain Metastases
Women with triple-negative breast cancer (TNBC) have the worst outcomes of all breast cancer patients due to the high propensity for brain metastases and lack of response to hormone or HER2-targeted therapies. Dr. Wang’s work to identify specific targets in TNBC cells that could be blocked to prevent brain lesions can provide TNBC patients with better outcomes and quality of life. Dr. Wang’s project is funded through a Department of Defense Breast Cancer Research Program Breakthrough Award.