Research Overview

The Escobar-Hoyos Lab is dedicated to outsmarting the most aggressive cancers. We investigate how pancreatic and lung tumors rewire their RNA biology to resist treatment and evade the immune system. By decoding these vulnerabilities, we design next-generation diagnostics and therapies—from precision biomarkers and "splicing-hit" oligonucleotides to innovative cancer vaccines—to offer new hope for patients with high-risk, therapy-resistant disease. We combine cutting-edge 'omics, pathology, and functional genomics to uncover the mechanisms of tumor aggression. Our research is built on three core pillars:

1. Targeting Aberrant RNA: We identify how cancer cells hijack their RNA programs and splicing machinery to survive and grow. This allows us to design novel therapeutics, including "splicing-hit" oligonucleotides, that correct these errors.
2. Leveraging Precision Biomarkers: We pioneered the use of Keratin 17 (K17) as a key biomarker that identifies the most lethal tumor subtypes. K17 guides our diagnostic platforms, helps predict chemotherapy response, and serves as a powerful therapeutic entry point.
3. Mobilizing the Immune System: We use our biological insights to "teach" the immune system to recognize and attack tumors. A major focus is developing antigen-mimicry cancer vaccines that make tumor cells appear like bacterial invaders, triggering a potent anti-cancer response.

Our group identified alternative RNA splicing as a therapeutic vulnerability in solid malignancies. We discovered that mutant p53 rewires RNA splicing to activate oncogenic KRAS in pancreatic cancer, creating therapeutic vulnerabilities. This led to the development of spliceosome inhibitors and oligonucleotide therapies, currently in clinical trials, to target these splicing defects and expand treatment options for patients with mutant p53 tumors.

• Siraj M, Zhang Y, Yugawa D, et al., Escobar-Hoyos LF. Nature Communications. 2024. PMID: 38233486.
• Pinto-Medici N, Quijano E, Ianniello Z, et al., Escobar-Hoyos LF. Gut. 2024. PMID: 38195325.
• Ianniello Z, Pinto-Medici N, Rackear M, Escobar-Hoyos LF. Trends Pharmacol Sci. 2022. PMID: 35715206.
• Polaski JT, Udy DB, et al., Escobar-Hoyos LF, Bradley RK. eLife. 2021. PMCID: PMC7846273.
• Escobar-Hoyos LF, Penson A, et al., Leach SD. Cancer Cell. 2020. PMCID: PMC8028848.
• Inoue D, Chew GL, Escobar-Hoyos LF, et al., Abdel-Wahab O, Bradley RK. Nature. 2019. PMCID: PMC6858540.
• Escobar-Hoyos LF, Knorr K, Abdel-Wahab O. Annual Review of Cancer Biology. 2019.

Our group discovered and validated a novel multi-modal cancer biomarker, Keratin 17 (K17). We identified Keratin 17 (K17) as an embryonic protein upregulated in various cancers, including cervical, bladder, and pancreatic. We validated K17 as an accurate diagnostic and prognostic biomarker, capable of predicting patient outcomes and chemotherapy response. Our lab has developed detection systems and filed patents for its clinical use.

• Chowdhury S, Yugawa D, et al., Escobar-Hoyos LF. Clinical Cancer Research. 2023. PMID: 37471016.
• Cecchini M, Salem RR, et al., Escobar-Hoyos LF, Lacy J. JAMA Oncology. 2023. PMID: 37589998.
• Babu S, Kim NW, et al., Escobar-Hoyos LF, Shroyer KR. Am J Clin Pathol. 2021. PMID: 34086841.
• Roa-Peña L, Leiton C, et al., Shroyer KR, Escobar-Hoyos LF. Scientific Reports. 2019. PMCID: PMC6677817.
• Escobar-Hoyos LF, Yang J, et al., Shroyer KR. Modern Pathology. 2014. PMCID: PMC4026928.

Our research group discovered a novel cancer therapeutic target by defining the oncogenic roles of K17. We demonstrated that K17 promotes tumor growth, metastasis, and chemotherapy resistance by interacting with nuclear proteins, degrading tumor suppressors, and disrupting cell proliferation pathways. This work revealed K17 as a critical oncogenic driver and a novel therapeutic target, challenging previous understandings of keratin function.

• Kawalerski RR, Torrente Gonçalves M, et al., Shroyer KR, Escobar-Hoyos LF. eLife. 2023. PMCID: PMC10651165.
• Baraks G, Tseng R, et al., Shroyer KR, Escobar-Hoyos LF. Cancer Research. 2022. PMID: 34921015.
• Hafeez F, Escobar-Hoyos LF, et al., Shroyer KR. Cancers (Basel). 2021. PMCID: PMC8534127.Pan CH, Otsuka Y, et al., Escobar-Hoyos LF, Shroyer KR. Molecular Oncology. 2020. PMID: 32533886.
• Escobar-Hoyos LF, Shah R, et al., Shroyer KR. Cancer Research. 2015. PMID: 26109559.

Our lab has identified factors that shape the immune landscape and trigger anti-tumor immunity. We showed that K17 expression in pancreatic cancer correlates with T-cell exclusion and macrophage presence, influencing the tumor microenvironment. Our work also explored the B-cell receptor repertoire as an immune predictor and proposed that splicing-derived neoantigens and driver mutations are key factors in immune infiltration, impacting immunotherapy strategies.

• Castellanos-Rueda R, Jaiswal A, et al., Escobar-Hoyos LF. JCI Insight. 2023. PMCID: PMC10313177.
• Fassler DJ, Zheng S, et al., Escobar-Hoyos LF, Shroyer KR. J Transl Med. 2021. PMCID: PMC8548971.
• Fassler DJ, Abousamra S, et al., Escobar-Hoyos LF, et al. Diagnostic Pathology. 2020. PMID: 32723384.
• Escobar-Hoyos LF, Abdel-Wahab O. Cancer Cell. 2018. PMID: 30107172.

Our work has impacted environmental policy by identifying factors that elevate cancer risk. We conducted extensive research using a biomarker of chromosome damage to assess cancer risk from water disinfection byproducts (DBPs), influencing the U.S. EPA's guidelines for DBP concentrations. Additionally, we investigated the role of genetic and environmental factors in DNA methylation and bladder cancer risk across diverse populations.

• Castro-Vega LJ, Garcés-Giraldo LF, et al., Escobar Hoyos LF. Sci Rep. 2021. PMCID: PMC8678250.
• Hoyos-Giraldo LS, Escobar-Hoyos LF, et al., Santella RM. J Expo Sci Environ Epidemiol. 2016. PMID: 25993025.
• Escobar-Hoyos LF, Hoyos-Giraldo LS, et al., Wagner ED, Plewa MJ. Water Research. 2013. PMID: 23602619.