MSTP in PhD Training
Program: Cancer Biology
Current advisor: Stephen Oh, MD, PhD
Undergraduate university: McGill University, 2016
Enrollment year: 2019
Novel therapeutic strategies for myeloid malignancies
This past year I worked in the lab of Dr. Stephen Oh in the Department of Hematology studying myeloproliferative neoplasms (MPN). Previous characterization of MPN (particularly myelofibrosis) and secondary AML patients in our lab revealed hyperactive activation of the NF-kB pathway, thus we investigated the efficacy of pevonedistat, a NEDD8-activating enzyme inhibitor which suppresses NF-kB signaling, as a viable therapeutic agent in these settings. We showed that pevonedistat reduced cancer proliferation in cell lines and colony growth in MPN and secondary AML patient primary samples. In mass cytometry studies, pevonedistat also inhibited hyperproduction of inflammatory cytokines and abrogated NF-kB activity in CD34+ cells from primary samples. Furthermore, pevonedistat treatment reduced disease burden and improved survival across multiple MPN mouse models. Our studies demonstrate pevonedistat could be an effective therapeutic for MPN patients, leading to initiation of a Phase I clinical trial.
Kong T, Laranjeira ABA, Yang K, Fisher DAC, Yu L, Poittevin De La Frégonnière L, Wang AZ, Ruzinova MB, Fowles JS, Fulbright MC, Cox MJ, Celik H, Challen GA, Huang S, Oh ST. 2023 DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression. Nat Cancer, 4(1):108-127.
Kong T, Laranjeira ABA, Collins TB, De Togni ES, Wong AJ, Fulbright MC, Ruzinova M, Celik H, Challen GA, Fisher DAC, Oh ST. 2022 Pevonedistat targets malignant cells in myeloproliferative neoplasms in vitro and in vivo via NFκB pathway inhibition. Blood Adv, 6(2):611-23.
Zhou A, Kong T, Fowles JS, Jung CL, Allen MJ, Fisher DAC, Fulbright M, Nemeth E, Ganz T, Oh ST. 2022 Hepcidin is elevated in primary and secondary myelofibrosis and remains elevated in patients treated with ruxolitinib. Br J Haematol, 197(4):e49-e52.