Terreia S. Jones, Pharm.D.
Dr. Jones obtained her Doctorate of Pharmacy degree from the University of Tennessee Health Science Center (UTHSC) and completed her post-graduate clinical training at the Veteran's Affairs Medical Center in Memphis, TN. She subsequently completed a fellowship in the Department of Pharmaceutical Sciences, St. Jude Children's Hospital focusing in pharmacogenomic studies of anticancer agents. Afterwards, she then joined the UTHSC Department of Clinical Pharmacy as Assistant Professor with secondary appointments in the Departments of Pharmaceutical Sciences and Neurosurgery.
Cancer affects people of all ages and remains one of the most devastating diseases both socially and economically. When considering cancers of the central nervous system, glioblastoma is the most common primary malignant brain tumor and is also the most deadly. The research focus of the Jones laboratory is to identify molecular factors that are important to the response to anticancer drug therapy with a primary goal of finding more effective and individualized approaches to treating malignant brain tumors.
Effects of glioma drug therapy on tumor and stromal cells
Malignant gliomas are cellularly complex with multiple stromal cell types contributing to the biology of the tumor and to treatment response [Jones and Holland. Oncogene September 2011]. Essentially all glioma patients are treated with radiation, chemotherapy, and corticosteroids, and these treatments ultimately modify the biology of the tumor especially in the setting of tumor recurrence. Models of glioma have been developed and these models allow us to look closely at how drug therapy influences specific nontumor cell populations (i.e. endothelial cells, microglia, etc) involved in gliomagenesis as well as the peritumoral microenvironment. The Jones laboratory is currently using genetically and histologically accurate models of glioma to understand the consequences of standard of care therapy on the biology of malignant glial tumors. The aim of this work is to identify novel drug targets as well as identify biomarkers of treatment efficacy and toxicity. This work is being conducted in collaboration with the Holland Lab at Memorial Sloan Kettering Cancer Center and the Gutmann Lab at Washington University.
Pharmacogenomics of anticancer therapy and treatment-associated tumorigenesis
Cancer is a disease that is dependent on a series of genetic alterations in order to develop, but is also dependent on individual genetic predisposition. One consequence of anticancer therapy is the possibility that a second cancer will form as a result of the therapy used to treat the primary cancer. In childhood leukemia, one of the more common late complications of antileukemic therapy is the development of a malignant glioma. It is possible that inter-individual genetic variations can put some patients at risk of developing a therapy-related second cancer. Thiopurine drugs are the backbone of antileukemic maintenance therapy and are also used as immunosuppressive agents in the transplant setting and for autoimmune disorders. Thiopurine drugs work primarily by generating cytotoxic lesions in the DNA of rapidly dividing cells (both cancerous and normal).
Thiopurine methyltransferase (Tpmt) is a well-known gene important to thiopurine drug metabolism and has been associated with the risk of brain tumor development after long-term therapy. Little is known about Tpmt's intrinsic role in the brain. The goals of this project are to determine whether Tpmt can influence the risk of brain tumor development after thiopurine exposure using relevant mouse models of glioma; and to identify other genetic factors that may predict who may be more likely to develop cancer after chronic thiopurines.
Pre-clinical and Translational Studies
For the past several decades, only modest advances have been made toward the development of more effective glioma therapies. Today, post surgical standard of care therapy includes temozolomide and radiation as antineoplastic therapy, dexamethosone for symptomatic relief, and now bevacizumab is used commonly at tumor recurrence. Indeed, the 5-year survival rate of patients diagnosed with a malignant glial tumor remains suboptimal (<10%) even when aggressive therapy is employed. Hence, there is a desperate need for more effective therapies to be developed against this disease. Dr. Jones is currently using models of glioma to test novel compounds developed by Dr. Duane Miller's Laboratory at UTHSC. Additionally, recent studies suggest that most human malignant gliomas can be grouped based on the molecular character of the tumor. It is hopeful that tumor characteristics can be used to better guide the selection of glioma drug therapy. The Jones lab is collaborating with local clinicians at The West Clinic and Semmes-Murphey Neurological and Spine Institute in Memphis, TN to study how patient factors and tumor character can influence or predict a patients response to glioma therapy.
Selected Peer-Reviewed Articles
- Ahmed A, Barnes J, Wan J, and Jones T. Thiopurine methyltransferase predicts the extent of cytotoxicity and DNA damage in astroglial cells after thioguanine exposure. PlosOne (Epub December 2011)
- Jones T and Holland E. Animal models for brain tumor drug discovery. Expert Opinion on Drug Discovery. October 2011 (Epub ahead of print)
- Jones T and Holland E. Standard of care therapy for malignant glioma and the effect on tumor and stromal cells. Oncogene. September 2011(Epub ahead of print)
- Jones T, Kaste S, Liu W, Cheng C, Yang W, Weiss S, Pui C-H, and Relling M. Corticotropin releasing hormone receptor-1 (CRHR1) polymorphisms predict bone density in acute lymphoblastic leukemia long-term survivors. Journal of Clinical Oncology. 2008 June; 26(18): 3031-3037.
- Jones T, Yang W, Evans W, and Relling M. Using HapMap Tools in Pharmacogenomic Discovery: The Thiopurine Methyltransferase Polymorphism. Clinical Pharmacology and Therapeutics. 2007 May; 81(5): 729-34.
- Jones T & Relling M (2011). Thiopurines. In A. Wu and KT Yeo (Eds.) Pharmacogenomic Testing in Current Clinical Practice: Implementation in the Clinical Laboratory. Human Press
- Jones T (2011). Pharmacogenetics and Pharmacogenomic. In D. Gourley (Ed), APhA International Foreign Graduate Equivalency Exam Review.
- Kuhl J, Jones T, Hanje J, & Motl S. (2007) Monoclonal Antibodies in Cancer. In J.A. Crommelin, R. Sindelar, & B. Meibohm (Eds.), Pharmaceutical Biotechnology: Fundamentals and Applications, Third Edition. Informa Health