Education & Certifications

  • BSc, University of Ottawa, Biochemistry (2019)
  • BASc, University of Ottawa, Chemical Engineering (2019)

All Publications

  • ΔNp63 regulates MDSC survival and metabolism in triple-negative breast cancer. iScience Kim, U., Debnath, R., Maiz, J. E., Rico, J., Sinha, S., Blanco, M. A., Chakrabarti, R. 2024; 27 (4): 109366


    Triple-negative breast cancer (TNBC) contributes greatly to mortality of breast cancer, demanding new targetable options. We have shown that TNBC patients have high ΔNp63 expression in tumors. However, the function of ΔNp63 in established TNBC is yet to be explored. In current studies, targeting ΔNp63 with inducible CRISPR knockout and Histone deacetylase inhibitor Quisinostat showed that ΔNp63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through tumor necrosis factor alpha. Decreasing ΔNp63 levels are associated with decreased CD4+ and FOXP3+ T-cells but increased CD8+ T-cells. RNA sequencing analysis indicates that loss of ΔNp63 alters multiple MDSC properties such as lipid metabolism, chemotaxis, migration, and neutrophil degranulation besides survival. We further demonstrated that targeting ΔNp63 sensitizes chemotherapy. Overall, we showed that ΔNp63 reprograms the MDSC-mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ΔNp63 in chemotherapy-resistant TNBC.

    View details for DOI 10.1016/j.isci.2024.109366

    View details for PubMedID 38510127

    View details for PubMedCentralID PMC10951988

  • KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs CANCER DISCOVERY Yan, F., Li, J., Milosevic, J., Petroni, R., Liu, S., Shi, Z., Yuan, S., Reynaga, J. M., Qi, Y., Rico, J., Yu, S., Liu, Y., Rokudai, S., Palmisiano, N., Meyer, S. E., Sung, P. J., Wan, L., Lan, F., Garcia, B. A., Stanger, B. Z., Sykes, D. B., Blanco, M. 2022; 12 (3): 792-811


    Epigenetic programs are dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. To identify key epigenetic regulators of AML cell fate, we performed a differentiation-focused CRISPR screen in AML cells. This screen identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drives critical leukemogenic gene-expression programs. We show that KAT6A is the initiator of a newly described transcriptional control module in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyl-lysine reader ENL, which in turn cooperates with a network of chromatin factors to induce transcriptional elongation. Inhibition of KAT6A has strong anti-AML phenotypes in vitro and in vivo, suggesting that KAT6A small-molecule inhibitors could be of high therapeutic interest for mono-therapy or combinatorial differentiation-based treatment of AML.AML is a poor-prognosis disease characterized by differentiation blockade. Through a cell-fate CRISPR screen, we identified KAT6A as a novel regulator of AML cell differentiation. Mechanistically, KAT6A cooperates with ENL in a "writer-reader" epigenetic transcriptional control module. These results uncover a new epigenetic dependency and therapeutic opportunity in AML. This article is highlighted in the In This Issue feature, p. 587.

    View details for Web of Science ID 000767244100001

    View details for PubMedID 34853079

    View details for PubMedCentralID PMC8916037

  • Chromatin-state barriers enforce an irreversible mammalian cell fate decision CELL REPORTS Blanco, M., Sykes, D. B., Gu, L., Wu, M., Petroni, R., Karnik, R., Wawer, M., Rico, J., Li, H., Jacobus, W. D., Jambhekar, A., Cheloufi, S., Meissner, A., Hochedlinger, K., Scadden, D. T., Shi, Y. 2021; 37 (6): 109967


    Stem and progenitor cells have the capacity to balance self-renewal and differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions and can increase this output in response to stress or infection. At what point along the spectrum of maturation do progenitors lose capacity for self-renewal and become irreversibly committed to differentiation? Using a system of conditional myeloid development that can be toggled between self-renewal and differentiation, we interrogate determinants of this "point of no return" in differentiation commitment. Irreversible commitment is due primarily to loss of open regulatory site access and disruption of a positive feedback transcription factor activation loop. Restoration of the transcription factor feedback loop extends the window of cell plasticity and alters the point of no return. These findings demonstrate how the chromatin state enforces and perpetuates cell fate and identify potential avenues for manipulating cell identity.

    View details for DOI 10.1016/j.celrep.2021.109967

    View details for Web of Science ID 000718274400006

    View details for PubMedID 34758323

  • Kinetic Model of Metabolism of Monoclonal Antibody Producing CHO Cells CURRENT METABOLOMICS Rico, J., Nantel, A., Phuong Lan Pham, Voyer, R., Durocher, Y., Penny, S., Surendra, A., Pinto, D., Sasseville, M., Culf, E., Leclerc, S., van het Hoog, M., Cuperlovic-Culf, M. 2018; 6 (3): 207-217