Sandra Carolina Ordonez Rubiano

All Publications

• Current Applications of Single-Cell RNA Sequencing in Glioblastoma: A Scoping Review BRAIN SCIENCES Ordonez-Rubiano, E. G., Rincon-Arias, N., Shelton, W. J., Salazar, A. F., Sierra, M., Bertani, R., Gomez-Amarillo, D. F., Hakim, F., Baldoncini, M., Payan-Gomez, C., Combita, A., Ordonez-Rubiano, S. C., Parra-Medina, R. 2025; 15 (3)

  Abstract

  Background and Objective: The discovery of novel molecular biomarkers via next-generation sequencing technologies has revolutionized how glioblastomas (GBMs) are classified nowadays. This has resulted in more precise diagnostic, prognostic, and therapeutic approaches to address this malignancy. The present work examines the applications of single-cell RNA sequencing (scRNA-seq) in GBM, focusing on its potential to address tumor complexity and therapeutic resistance and improve patient outcomes. Methods: A scoping review of original studies published between 2009 and 2024 was conducted using the PUBMED and EMBASE databases. Studies in English or Spanish related to single-cell analysis and GBM were included. Key Findings: The database search yielded 453 publications. Themes related to scRNA-seq applied for the diagnosis, prognosis, treatment, and understanding of the cancer biology of GBM were used as criteria for article selection. Of the 24 studies that were included in the review, 11 focused on the tumor microenvironment and cell subpopulations in GBM samples, 5 investigated the use of sequencing to elucidate the GBM cancer biology, 3 examined disease prognosis using sequencing models, 3 applied translational research through scRNA-seq, and 2 addressed treatment-related problems in GBM elucidated by scRNA-seq. Conclusions: This scoping review explored the various clinical applications of scRNA-seq technologies in approaching GBM. The findings highlight the utility of this technology in unraveling the complex cellular and immune landscapes of GBM, paving the way for improved diagnosis and personalized treatments. This cutting-edge approach might strengthen treatment strategies against tumor progression and recurrence, setting the stage for multi-targeted interventions that could significantly improve outcomes for patients with aggressive, treatment-resistant GBMs.

  View details for DOI 10.3390/brainsci15030309

  View details for Web of Science ID 001453034100001

  View details for PubMedID 40149830

  View details for PubMedCentralID PMC11940614

• Rational Design and Development of Selective BRD7 Bromodomain Inhibitors and Their Activity in Prostate Cancer JOURNAL OF MEDICINAL CHEMISTRY Ordonez-Rubiano, S. C., Maschinot, C. A., Wang, S., Sood, S., Baracaldo-Lancheros, L. F., Strohmier, B. P., McQuade, A. J., Smith, B. C., Dykhuizen, E. C. 2023; 66 (16): 11250-11270

  Abstract

  Bromodomain-containing proteins are readers of acetylated lysine and play important roles in cancer. Bromodomain-containing protein 7 (BRD7) is implicated in multiple malignancies; however, there are no selective chemical probes to study its function in disease. Using crystal structures of BRD7 and BRD9 bromodomains (BDs) bound to BRD9-selective ligands, we identified a binding pocket exclusive to BRD7. We synthesized a series of ligands designed to occupy this binding region and identified two inhibitors with increased selectivity toward BRD7, 1-78 and 2-77, which bind with submicromolar affinity to the BRD7 BD. Our binding mode analyses indicate that these ligands occupy a uniquely accessible binding cleft in BRD7 and maintain key interactions with the asparagine and tyrosine residues critical for acetylated lysine binding. Finally, we validated the utility and selectivity of the compounds in cell-based models of prostate cancer.

  View details for DOI 10.1021/acs.jmedchem.3c00671

  View details for Web of Science ID 001044532300001

  View details for PubMedID 37552884

  View details for PubMedCentralID PMC10641717

• Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening. Journal of medicinal chemistry Shishodia, S., Nuñez, R., Strohmier, B. P., Bursch, K. L., Goetz, C. J., Olp, M. D., Jensen, D. R., Fenske, T. G., Ordonez-Rubiano, S. C., Blau, M. E., Roach, M. K., Peterson, F. C., Volkman, B. F., Dykhuizen, E. C., Smith, B. C. 2022; 65 (20): 13714-13735

  Abstract

  PBRM1 is a subunit of the PBAF chromatin remodeling complex that uniquely contains six bromodomains. PBRM1 can operate as a tumor suppressor or tumor promoter. PBRM1 is a tumor promoter in prostate cancer, contributing to migratory and immunosuppressive phenotypes. Selective chemical probes targeting PBRM1 bromodomains are desired to elucidate the association between aberrant PBRM1 chromatin binding and cancer pathogenesis and the contributions of PBRM1 to immunotherapy. Previous PBRM1 inhibitors unselectively bind SMARCA2 and SMARCA4 bromodomains with nanomolar potency. We used our protein-detected NMR screening pipeline to screen 1968 fragments against the second PBRM1 bromodomain, identifying 17 hits with Kd values from 45 μM to >2 mM. Structure-activity relationship studies on the tightest-binding hit resulted in nanomolar inhibitors with selectivity for PBRM1 over SMARCA2 and SMARCA4. These chemical probes inhibit the association of full-length PBRM1 to acetylated histone peptides and selectively inhibit growth of a PBRM1-dependent prostate cancer cell line.

  View details for DOI 10.1021/acs.jmedchem.2c00864

  View details for PubMedID 36227159

  View details for PubMedCentralID PMC9630929

• Polycomb group proteins in cancer: multifaceted functions and strategies for modulation. NAR cancer Wang, S., C Ordonez-Rubiano, S., Dhiman, A., Jiao, G., Strohmier, B. P., Krusemark, C. J., Dykhuizen, E. C. 2021; 3 (4): zcab039

  Abstract

  Polycomb repressive complexes (PRCs) are a heterogenous collection of dozens, if not hundreds, of protein complexes composed of various combinations of subunits. PRCs are transcriptional repressors important for cell-type specificity during development, and as such, are commonly mis-regulated in cancer. PRCs are broadly characterized as PRC1 with histone ubiquitin ligase activity, or PRC2 with histone methyltransferase activity; however, the mechanism by which individual PRCs, particularly the highly diverse set of PRC1s, alter gene expression has not always been clear. Here we review the current understanding of how PRCs act, both individually and together, to establish and maintain gene repression, the biochemical contribution of individual PRC subunits, the mis-regulation of PRC function in different cancers, and the current strategies for modulating PRC activity. Increased mechanistic understanding of PRC function, as well as cancer-specific roles for individual PRC subunits, will uncover better targets and strategies for cancer therapies.

  View details for DOI 10.1093/narcan/zcab039

  View details for PubMedID 34617019

  View details for PubMedCentralID PMC8489530

• A Potent, Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation. Chembiochem : a European journal of chemical biology Wang, S., Alpsoy, A., Sood, S., Ordonez-Rubiano, S. C., Dhiman, A., Sun, Y., Jiao, G., Krusemark, C. J., Dykhuizen, E. C. 2021; 22 (13): 2335-2344

  Abstract

  Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N-terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a Kd of 80 nM and displays 24-1000-fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.

  View details for DOI 10.1002/cbic.202100118

  View details for PubMedID 33950564

  View details for PubMedCentralID PMC8358665