Tim Kong
Program: Cancer Biology
Current advisor: Stephen Oh, MD, PhD
Undergraduate university: McGill University
Research summary
I work in the lab of Dr. Stephen Oh in the Department of Hematology. Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Using multi-omic approaches such as single cell RNA-seq, suspension mass cytometry, ATAC-Seq, and CUT&Tag, we identify novel effectors that can be targeted therapeutically. Targeting of one identified candidate, RSK1, suppressed NFκB activation and diminished pro-inflammatory mediators including tumor necrosis factor associated with leukemic disease severity and transformation. We further evaluated a novel therapeutic approach utilizing a first-in-class RSK inhibitor, PMD-026, currently in Phase 2 development for breast cancer, for use in myeloid malignancies. Treatment with PMD-026 suppressed disease burden across syngeneic and patient-derived xenograft leukemia mouse models spanning the spectrum of driver and disease-modifying mutations. These findings uncover a novel therapeutic avenue for a conserved dependency across blood cancers.
Graduate publications
Laranjeira ABA, Kong T, Snyder SC, Fulbright MC, Fisher DAC, Starczynowski DT, Oh ST. 2024 In vivo ablation of NFκB cascade effectors alleviates disease burden in myeloproliferative neoplasms. Blood, ():Online ahead of print.
He F, Laranjeira AB, Kong T, Lin S, Ashworth KJ, Liu A, Lasky NM, Fisher DA, Cox MJ, Fulbright MC, Antunes-Heck L, Yu L, Brakhane M, Gao B, Sykes SM, D’Alessandro A, Di Paola J, Oh ST. 2024 Multiomic profiling reveals metabolic alterations mediating aberrant platelet activity and inflammation in myeloproliferative neoplasms. J Clin Invest, 343(3):e172256.
Kong T, Gaudin N, Gordon K, Cox MJ, Zhou AW, Oh ST. 2024 A phase I trial of pevonedistat in combination with ruxolitinib for the treatment of myelofibrosis. Ther Adv Hematol, 15():20406207241237607..
Collins TB, Laranjeira ABA, Kong T, Fulbright MC, Fisher DAC, Sturgeon CM, Batista LFZ, Oh ST. 2024 Altered erythropoiesis via JAK2 and ASXL1 mutations in myeloproliferative neoplasms. Exp Hematol, 132():104178.
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.
Oh ST, Mesa RA, Harrison CN, Bose P, Gerds AT, Gupta V, Scott BL, Kiladjian JJ, Lucchesi A, Kong T, Buckley SA, Tyavanagimatt S, Harder BG, Roman-Torres K, Smith J, Craig AR, Mascarenhas J, Verstovsek S. 2023 Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood Adv, 7(19):5835-42.
Kong T, Yu L, Laranjeira ABA, Fisher DAC, He F, Cox MJ, Oh ST. 2023 Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms. Am J Hematol, 98(7):1029-42.
Fisher DAC, Laranjeira ABA, Kong T, Snyder SC, Shim K, Fulbright MC, Oh ST. 2023 Complementary and countervailing actions of Jak2 and Ikk2 in hematopoiesis in mice. Exp Hematol, 128():48-66.
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.