Quenton Rashawn Bubb

All Publications

• Post-transplant cyclophosphamide vs tacrolimus/methotrexate: Improved GRFS, reduced NRM, and less severe GVHD in myeloablative HLA-matched allogeneic transplantation Molina, A., Bubb, Q., Yee, R., Arai, S., Bharadwaj, S., Dahiya, S., Elmariah, H., Frank, M., Hosoya, H., Johnston, L., Meyer, E., Mikkilineni, L., Lowsky, R., Negrin, R., Rezvani, A., Shizuru, J., Sidana, S., Smith, M., Weng, W., Miklos, D., Muffly, L., Kennedy, V. ELSEVIER. 2025: 2494-2495

  View details for DOI 10.1182/blood-2025-2494

  View details for Web of Science ID 001659232500044

• Transcriptomic Diversity of Pediatric Acute Myeloid Leukemia Genetic Drivers Correlates With Clinical Outcome and Expression of Stemness-Related Genes. Cancer medicine Bubb, Q. R., Sotillo, E., Richards, R. M., Mackall, C. L., Gruber, T. A., Czechowicz, A. 2025; 14 (21): e71325

  Abstract

  Pediatric acute myeloid leukemia (pAML) is comprised of a diverse set of oncogenic drivers (ODs) that have been risk-stratified to inform prognosis and therapeutic decision-making. Despite proteomic, transcriptomic, genetic, and epigenetic characterization of the pAML landscape, questions still remain about why certain ODs have poorer prognoses than others.We analyze a large pAML bulk-RNA dataset (n = 435) and organize ODs along an axis of transcriptomic diversity by calculating the Simpson Diversity Index (SDI) of individual ODs.When comparing patients with low diversity ODs to patients with high diversity ODs, we observe poorer overall survival (HR = 1.877, 95% CI: 1.377-2.558, p = 0.0002) among patients harboring high diversity ODs in addition to an enrichment of stemness-related genes. We observe poorer survival of patients with high diversity ODs even when comparing patients with similar transcriptomic profiles (HR = 3.443, 95% CI: 1.817-6.525, p = 0.0028).We identify a link between transcriptomic diversity, expression of stemness-related genes, and clinical outcome. Higher transcriptomic heterogeneity exhibited by high diversity ODs warrants further attention when identifying patients who can benefit from novel or high-intensity therapy.

  View details for DOI 10.1002/cam4.71325

  View details for PubMedID 41178390

  View details for PubMedCentralID PMC12580620

• Development of multivalent CAR T cells as dual immunotherapy and conditioning agents MOLECULAR THERAPY ONCOLOGY Bubb, Q., Balood, M., Seir, G., Swartzrock, L., Haslett, E., Ho, K., Xu, P., Wiltz, S. G., Sotillo, E., Gruber, T. A., Richards, R. M., Mackall, C. L., Czechowicz, A. 2025; 33 (1)

  View details for DOI 10.1016/j.omton.2025.200944

  View details for Web of Science ID 001428530900001

• Development of multivalent CAR T cells as dual immunotherapy and conditioning agents. Molecular therapy. Oncology Bubb, Q. R., Balood, M., Seir, G. E., Swartzrock, L., Haslett, E., Ho, K., Xu, P., Wiltz, S. G., Sotillo, E., Gruber, T. A., Richards, R. M., Mackall, C. L., Czechowicz, A. 2025; 33 (1): 200944

  Abstract

  Hematopoietic stem cell transplantation (HSCT) is the only definitive cure for pediatric acute myeloid leukemia (AML). Despite adjustments in HSCT protocols and improvements in supportive care, 30% of high-risk patients who receive HSCT as part of their therapy still experience disease relapse with high transplant-related mortality. Relapsed AML has a dismal prognosis, and novel therapies are needed. To improve upon the status quo, HSCT would more effectively eliminate relapse-initiating leukemic cells and be delivered with safer, non-genotoxic conditioning. Here, we investigate hematopoietic cytokine receptors (HCRs) and identify that KIT, MPL, and FLT3 are collectively highly expressed in virtually all pediatric AML samples studied. Further, we establish proof-of-concept of a first-in-class chimeric antigen receptor (CAR) T cell that enables simultaneous targeting of KIT, MPL, and FLT3 through a single receptor, which we term the extracellularly linked concatemeric trivalent cytokine (ELECTRIC) CAR. ELECTRIC CARs exhibit potent cytotoxicity against normal and malignant hematopoietic cells in vitro and display anti-HCR activity in a murine xenograft model. We propose that the ELECTRIC system can be the foundation to developing a non-genotoxic, anti-leukemic conditioning regimen to enable safer, more durable efficacy with minimal toxicity.

  View details for DOI 10.1016/j.omton.2025.200944

  View details for PubMedID 40034967

  View details for PubMedCentralID PMC11872492

• Development of Extracellularly Linked Concatemeric Trivalent Cytokine (ELeCTriC) Chimeric Antigen Receptor (CAR) T-Cells as Dual Conditioning and Immunotherapeutic Agents Bubb, Q. R., Balood, M., Seir, G. E., Swartzrock, L., Haslett, E., Ho, K., Wiltz, S. G., Sotillo, E., Richards, R. M., Gruber, T. A., Mackall, C. L., Czechowicz, A. CELL PRESS. 2024: 75

  View details for Web of Science ID 001332783400138

• Hematopoiesis post anti-CD117 monoclonal antibody treatment in wild-type and Fanconi anemia settings. Haematologica Denis, M., Swartzrock, L., Willner, H., Bubb, Q. R., Haslett, E., Chan, Y. Y., Chen, A., Krampf, M. R., Czechowicz, A. D. 2024

  Abstract

  Anti-CD117 monoclonal antibody (mAb) agents have emerged as exciting alternative conditioning strategies to traditional genotoxic irradiation or chemotherapy conditioning for both allogeneic and autologous gene-modified hematopoietic stem cell transplantation. Further, these agents are concurrently being explored in the treatment of mast cell disorders. Despite promising results in animal models and more recently in patients, the short-term and long-term effects of these treatments have not been fully explored. We conducted rigorous assessments to evaluate the effects of antagonistic anti-mCD117 mAb, ACK2, on hematopoiesis in wild-type (WT) and Fanconi Anemia (FA) mice. Importantly, we found no evidence of short-term DNA damage in either setting following this treatment suggesting that ACK2 does not induce immediate genotoxicity, providing crucial insights into its safety profile. Surprisingly, FA mice exhibited an increase in colony formation post-ACK2 treatment without accompanying DNA damage, indicating a potential targeting of hematopoietic stem cells (HSCs) and expansion of hematopoietic progenitor cells. Moreover, the long-term phenotypic and functional changes in hematopoietic stem and progenitor cells did not significantly differ between the ACK2-treated and control groups, in either setting, supporting that ACK2 does not adversely affect hematopoietic capacity. These finding underscore the safety of these agents when utilized as a short-course treatment in the conditioning context, as they did not induce significant changes in DNA damage amongst hematopoietic stem or progenitor cells. However, through a comparison of gene expression via single-cell RNA sequencing between untreated and treated mice, it was revealed that the ACK2 mAb, via c-Kit downregulation, effectively modulated the MAPK pathway with Fos down-regulation in WT and FA mice. Importantly, this modulation was achieved without causing prolonged disruptions. These findings validate the safety of the treatment and also enhance our understanding of its intricate mode of action at the molecular level.

  View details for DOI 10.3324/haematol.2023.284275

  View details for PubMedID 38572555

• Folding and binding pathways of BH3-only proteins are encoded within their intrinsically disordered sequence, not templated by partner proteins JOURNAL OF BIOLOGICAL CHEMISTRY Crabtree, M. D., Mendonca, C. F., Bubb, Q. R., Clarke, J. 2018; 293 (25): 9718–23

  Abstract

  Intrinsically disordered regions are present in one-third of eukaryotic proteins and are overrepresented in cellular processes such as signaling, suggesting that intrinsically disordered proteins (IDPs) may have a functional advantage over folded proteins. Upon interacting with a partner macromolecule, a subset of IDPs can fold and bind to form a well-defined three-dimensional conformation. For example, disordered BH3-only proteins bind promiscuously to a large number of homologous BCL-2 family proteins, where they fold to a helical structure in a groove on the BCL-2-like protein surface. As two protein chains are involved in the folding reaction, and the structure is only formed in the presence of the partner macromolecule, this raises the question of where the folding information is encoded. Here, we examine these coupled folding and binding reactions to determine which component determines the folding and binding pathway. Using Φ value analysis to compare transition state interactions between the disordered BH3-only proteins PUMA and BID and the folded BCL-2-like proteins A1 and MCL-1, we found that, even though the BH3-only protein is disordered in isolation and requires a stabilizing partner to fold, its folding and binding pathway is encoded in the IDP itself; the reaction is not templated by the folded partner. We suggest that, by encoding both its transition state and level of residual structure, an IDP can evolve a specific kinetic profile, which could be a crucial functional advantage of disorder.

  View details for DOI 10.1074/jbc.RA118.002791

  View details for Web of Science ID 000436102300016

  View details for PubMedID 29716994

  View details for PubMedCentralID PMC6016464