Courtney Jones

At a Glance

• The goal of our research is to improve outcomes for patients with leukemia
• The focus of the lab includes leukemia stem cell biology and metabolism
• All work is performed using primary leukemia specimens
• We are working to translate studies from the laboratory into the clinic and understand clinical observations through laboratory studies.

Short Bio

Courtney Jones is a Scientist at the Princess Margaret Cancer Centre, University Health Network, and Assistant Professor in the Dept. of Medical Biophysics at the University of Toronto. Dr. Jones received her doctorate from New York University in 2014 studying mechanisms of therapy resistance in pediatric acute lymphoblastic leukemia. She continued her training as a postdoctoral fellow with Dr. Craig Jordan at the University of Colorado where she studied metabolic properties of leukemia stem cells (LSCs).

The overall goal of Dr. Jones and her team is to identify, characterize, and target metabolic vulnerabilities of LSCs in order to improve outcomes for patients with leukemia. To achieve this goal her lab uses primary leukemia specimens, patient-derived xenograft models, as well as mass spectrometry-based metabolomic and lipidomic analysis. The ultimate objective of the lab is to translate our laboratory findings into the clinic and understand clinical observations through laboratory studies.

Research Synopsis

The goal of our laboratory is to develop better therapies to treat patients with acute myeloid leukemia. In leukemia, like many other cancer types, a small subset of cells called cancer stem cells are thought to drive disease initiation, pathogenesis and relapse. While conventional cytotoxic chemotherapies often reduce the bulk tumor, developing therapeutic strategies to target cancer stem cells has been more challenging. In acute myeloid leukemia, the most common form of adult acute leukemia, the long-term survival rate is approximately 21%; therefore, therapies designed to eradicate leukemia stem cells (LSCs) are urgently needed.

LSCs have unique properties that differentiate them from the bulk leukemic cells and normal blood stem cells. One property that differentiates LSCs from other cells is their unique metabolic requirements. Our lab studies LSC metabolism with the objective of identifying therapeutic strategies to target LSC specific metabolic properties resulting in LSC death. For example, we know that LSCs are highly reliant on oxidative phosphorylation for survival. Current efforts in the lab focus on identifying and targeting pathways that regulate oxidative phosphorylation including amino acid metabolism, glutathione biology, and mitochondrial sirtuins.

Recent Publications

Pei, S., D. A. Pollyea, A. Gustafson, B. M. Stevens, M. Minhajuddin, R. Fu, K. A. Riemondy, A. E. Gillen, R. M. Sheridan, J. Kim, J. C. Costello, M. L. Amaya, A. Inguva, A. Winters, H. Ye, A. Krug, C. L. Jones, B. Adane, N. Khan, J. Ponder, J. Schowinsky, D. Abbott, A. Hammes, J. R. Myers, J. M. Ashton, T. Nemkov, A. D'Alessandro, J. A. Gutman, H. E. Ramsey, M. R. Savona, C. A. Smith and C. T. Jordan (2020). "Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Acute Myeloid Leukemia Patients." Cancer Discovery: CD-19-0710.

Jones C.L., Stevens BM, D'Alessandro A, Culp-Hill R, Reisz JA, Pei S, Gustafson A, Khan N1, DeGregori J, Pollyea DA, Jordan CT. Cysteine depletion targets leukemia stem cells through inhibition of electron transport complex II. Blood, doi:10.1182/blood.2019898114 (2019).

Nechiporuk, T., S. E. Kurtz, O. Nikolova, T. Liu, C. L. Jones, A. D'Alessandro, R. Culp-Hill, A. d'Almeida, S. K. Joshi, M. Rosenberg, C. E. Tognon, A. V. Danilov, B. J. Druker, B. H. Chang, S. K. McWeeney and J. W. Tyner (2019). "The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells." Cancer Discov 9(7): 910-925.

Adane, B., H. Ye, N. Khan, S. Pei, M. Minhajuddin, B. M. Stevens, C. L. Jones, A. D'Alessandro, J. A. Reisz, V. Zaberezhnyy, M. Gasparetto, T. C. Ho, K. K. Kelly, J. R. Myers, J. M. Ashton, J. Siegenthaler, T. Kume, E. L. Campbell, D. A. Pollyea, M. W. Becker and C. T. Jordan (2019). "The Hematopoietic Oxidase NOX2 Regulates Self-Renewal of Leukemic Stem Cells." Cell Rep 27(1): 238-254.e236.

Jones, C.L., Stevens, B.M., D'Alessandro, A., Reisz, J.A., Culp-Hill, R., Nemkov, T., Pei, S., Khan, N., Adane, B., Ye, H., Reinhold, D., Smith, C., DeGregori, J., Pollyea, D.A., Jordan, C.T.. Inhibition of Amino Acid Metabolism Selectively Targets Human Leukemia Stem Cells. Cancer Cell, 2018;34(5):724-740.e724.

Pollyea, D.A.*, Stevens, B.M.*, Jones, C.L.*, Winters, A., Pei, S., Minhajuddin, M., D’Alessandro, A. Culp-Hill, R., Riemondy, K.A., Gillen, A.E., Hesselberth, J.R., Abbott, D., Schatz, D., Gutman, J.A., Purev, E., Smith, C., Jordan, C.T. Venetoclax with Azacitidine Disrupts Energy Metabolism and Targets Leukemia Stem Cells in Acute Myeloid Leukemia Patients. Nature Medicine, 2018;24(12):1859-1866.

Stevens, B.M., Khan, N., D’Alessandro, A., Nemkov, N., Winters, A., Jones, C.L., Zhang, W., Pollyea D.A., Jordan, C.T. Characterization and targeting of malignant stem cells in patients with advanced myelodysplastic syndromes, 2018; Nature Communications 9, 3694.

Graduate Students

Tianyi Charlotte Ling
Cristiana O'Brien