Luisa Escobar-Hoyos, MSc, PhD
Research & Publications
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Extensive Research Description
Despite recent targeted- and immune-therapies that have benefitted other cancer types, pancreatic and lung tumors develop therapy resistance. Therefore, there is an urgent clinical need to better understand the molecular biology of this disease to enable the improvement of therapeutic strategies.
Activating mutations in KRAS and p53 co-occur in 40% of pancreatic and lung and other tumors. We recently addressed the long-standing question of how these most common co-occurring mutations in human cancers cooperate to cause tumors, hoping to identify a meaningful therapeutic opportunity. We demonstrated that altered RNA splicing by mutant p53 activates and maintains oncogenic KRAS signaling. These paradigm shifting studies led to discovering that oncogenic KRAS is susceptible to inactivation, a novel finding in the field, and suggested the likelihood that inhibiting RNA splicing represents a valuable therapeutic strategy for mutant KRAS/p53 tumors (Cancer Cell 2020).
Therefore, our research focuses on understanding how aberrant RNA splicing contributes to the maintenance, establishment, and impairment of anti-tumor immune response in tumors. Additionally, we aim to test our novel developed therapy, called Splicing-Hit Oligonucleotide Therapy (SHOT), which corrects the RNA splicing errors selectively killing PDAC and LUAD cells of our own genetically engineered mouse models (GEMM) to recapitulate the human PDAC background and to validate our findings. Compared to traditional targeted therapies where it takes years to generate a compound or antibody to inhibit mutant proteins, SHOT enables rapid and precise therapy development. SHOTs are adaptable and scalable, to be used against second-line therapy resistant cancers or to target more than one cancer type.
Our laboratory collaborates actively with laboratories at Yale University, Stony Brook University, and Memorial Sloan Kettering Cancer Center. Our team involves experts within backgrounds spanning oncology, immunology, bioinformatics, drug delivery, and microbiology. We believe that through this collaborative environment, we will achieve our ultimate goals in hopes of developing new efficient therapies that can ultimately lead to the cure of this devastating malignancy.
Coauthors
Research Interests
Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; RNA Splicing
Selected Publications
- Perioperative Modified FOLFIRINOX for Resectable Pancreatic CancerCecchini M, Salem R, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend J, Cai G, Chowdhury S, Yugawa D, Tseng R, Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan S, Cha C, Billingsley K, Kunstman J, Johung K, Wiess C, Muzumdar M, Spickard E, Aushev V, Laliotis G, Jurdi A, Liu M, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer. JAMA Oncology 2024, 10 PMID: 38900452, PMCID: PMC11190830, DOI: 10.1001/jamaoncol.2024.1575.
- Keratin 17 modulates the immune topography of pancreatic cancerDelgado-Coka L, Horowitz M, Torrente-Goncalves M, Roa-Peña L, Leiton C, Hasan M, Babu S, Fassler D, Oentoro J, Bai J, Petricoin E, Matrisian L, Blais E, Marchenko N, Allard F, Jiang W, Larson B, Hendifar A, Chen C, Abousamra S, Samaras D, Kurc T, Saltz J, Escobar-Hoyos L, Shroyer K. Keratin 17 modulates the immune topography of pancreatic cancer. Journal Of Translational Medicine 2024, 22: 443. PMID: 38730319, PMCID: PMC11087249, DOI: 10.1186/s12967-024-05252-1.
- Keratin 17 is a prognostic and predictive biomarker in pancreatic ductal adenocarcinomaDelgado-Coka L, Roa-Peña L, Babu S, Horowitz M, Petricoin E, Matrisian L, Blais E, Marchenko N, Allard F, Akalin A, Jiang W, Larson B, Hendifar A, Picozzi V, Choi M, Shroyer K, Escobar-Hoyos L. Keratin 17 is a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma. American Journal Of Clinical Pathology 2024, aqae038. PMID: 38642081, DOI: 10.1093/ajcp/aqae038.
- Abstract LB299: Dihydrouridine synthase 2 sustains levels of tRNACys and prevents ferroptosis in lung cancerDraycott A, Wang M, Saucedo D, Escobar-Hoyos L, Gilbert W. Abstract LB299: Dihydrouridine synthase 2 sustains levels of tRNACys and prevents ferroptosis in lung cancer. Cancer Research 2024, 84: lb299-lb299. DOI: 10.1158/1538-7445.am2024-lb299.
- Abstract A072: Keratin 17-signature for stratification of chemotherapy in pancreatic adenocarcinomaChowdhury S, Yugawa D, Tseng R, Mejia M, Lacy J, Patel T, Escobar-Hoyos L, Shroyer K, Cai G, Robert M, Cecchini M, Kunstman J, Farrell J, Johung K. Abstract A072: Keratin 17-signature for stratification of chemotherapy in pancreatic adenocarcinoma. Cancer Research 2024, 84: a072-a072. DOI: 10.1158/1538-7445.panca2023-a072.
- Abstract A068: Proteomic analysis of keratin 17 positive cells from laser-capture microdissected pancreatic ductal adenocarcinomaBai J, Haley J, Marchenko N, Escobar-Hoyos L, Shroyer K. Abstract A068: Proteomic analysis of keratin 17 positive cells from laser-capture microdissected pancreatic ductal adenocarcinoma. Cancer Research 2024, 84: a068-a068. DOI: 10.1158/1538-7445.panca2023-a068.
- Abstract B012: TP53 missense mutations and keratin 17 are negative prognostic biomarkers in pancreatic ductal adenocarcinomaArbelaez C, Baraks G, Oblein L, Horowitz M, Matrisian L, Shroyer K, Escobar-Hoyos L. Abstract B012: TP53 missense mutations and keratin 17 are negative prognostic biomarkers in pancreatic ductal adenocarcinoma. Cancer Research 2024, 84: b012-b012. DOI: 10.1158/1538-7445.panca2023-b012.
- Abstract B041: Keratin 17 excludes CD8-positive T cells and recruits CD163-positive macrophages in pancreatic ductal adenocarcinomaOblein L, Babu S, Torrente-Goncalves M, Roa L, Horowitz M, Hasan M, Fassler D, Oentoro J, Petricoin E, Matrisian L, Marchenko N, Blais E, Allard F, Alkalin A, Jiang W, Larson B, Hendifar A, Chen C, Abousamra S, Samaras D, Kurc T, Saltz J, Escobar-Hoyos L, Shroyer K. Abstract B041: Keratin 17 excludes CD8-positive T cells and recruits CD163-positive macrophages in pancreatic ductal adenocarcinoma. Cancer Research 2024, 84: b041-b041. DOI: 10.1158/1538-7445.panca2023-b041.
- Abstract B065: Biomarker approach to define tumor subtype in pancreatic ductal adenocarcinomaHo C, Horowitz M, Oblein L, Sarkar S, Kobayashi S, Bai K, Marchenko N, Escobar-Hoyos L, Shroyer K. Abstract B065: Biomarker approach to define tumor subtype in pancreatic ductal adenocarcinoma. Cancer Research 2024, 84: b065-b065. DOI: 10.1158/1538-7445.panca2023-b065.
- Abstract B066: Keratin 17 and GATA6 expression in pancreatic ductal adenocarcinoma: A subtyping stratification approachHorowitz M, Oblein L, Oentoro J, Porwal A, Jiang W, Marchenko N, Escobar-Hoyos L, Shroyer K. Abstract B066: Keratin 17 and GATA6 expression in pancreatic ductal adenocarcinoma: A subtyping stratification approach. Cancer Research 2024, 84: b066-b066. DOI: 10.1158/1538-7445.panca2023-b066.
- Abstract B085: K17-induced pyrimidine biosynthesis drives chemoresistance in PDACLyu Y, Shroyer K, Pan C, Tseng R, Siraj M, Rajacharya G, Chen B, Donnelly K, Horowitz M, Mejia Arbelaez C, Chowdhury S, Oblein L, Marchenko N, Escobar-Hoyos L, Singh P. Abstract B085: K17-induced pyrimidine biosynthesis drives chemoresistance in PDAC. Cancer Research 2024, 84: b085-b085. DOI: 10.1158/1538-7445.panca2023-b085.
- Abstract B115: Single-cell transcriptomic analysis reveals both shared and separate functions for GATA6 and KRT17 in pancreatic cancerNelson B, Marchenko N, Escobar-Hoyos L, Shroyer K, Powers S, MacCarthy T. Abstract B115: Single-cell transcriptomic analysis reveals both shared and separate functions for GATA6 and KRT17 in pancreatic cancer. Cancer Research 2024, 84: b115-b115. DOI: 10.1158/1538-7445.panca2023-b115.
- Abstract C050: The unique metabolic signatures of keratin-17 expressing pancreatic ductal adenocarcinomasSalem M, Horowitz M, Oblein L, Pan C, Marchenko N, Escobar-Hoyos L, Chen B, Shroyer K. Abstract C050: The unique metabolic signatures of keratin-17 expressing pancreatic ductal adenocarcinomas. Cancer Research 2024, 84: c050-c050. DOI: 10.1158/1538-7445.panca2023-c050.
- Abstract C063: Keratin 17 as a predictor of chemotherapy response in pancreatic ductal adenocarcinomaOblein L, Roa L, Babu S, Horowitz M, Petricoin E, Matrisian L, Blais E, Marchenko N, Allard F, Alkalin A, Jiang W, Larson B, Hendifar A, Picozzi V, Choi M, Escobar-Hoyos L, Shroyer K. Abstract C063: Keratin 17 as a predictor of chemotherapy response in pancreatic ductal adenocarcinoma. Cancer Research 2024, 84: c063-c063. DOI: 10.1158/1538-7445.panca2023-c063.
- Abstract C067: Correlation of keratin17 expression with tumor cell proliferation and invasion in PDACSarkar S, Oblein L, Horowitz M, Escobar-Hoyos L, Marchenko N, Shroyer K. Abstract C067: Correlation of keratin17 expression with tumor cell proliferation and invasion in PDAC. Cancer Research 2024, 84: c067-c067. DOI: 10.1158/1538-7445.panca2023-c067.
- Abstract C075: Altered RNA splicing causes pancreatic cancer and exposes a therapeutic vulnerabilityMedici N, Saucedo D, Lee D, Ku L, Tseng R, Shan X, Chu T, Perez-Piñera P, Cannataro V, Townsend J, Iacobuzio-Donahue C, Robert M, Abdel-Wahab O, Leach S, Escobar-Hoyos L. Abstract C075: Altered RNA splicing causes pancreatic cancer and exposes a therapeutic vulnerability. Cancer Research 2024, 84: c075-c075. DOI: 10.1158/1538-7445.panca2023-c075.
- Abstract C083: SMNDC1 alters the splicing of ERK to potentiate its activity in pancreatic cancerSiraj M, Zhang Y, Chakraborty P, Tseng R, Ku L, Goda G, Giri G, Yugawa D, Wang M, Das S, Dey A, Dwivedi S, Rao G, Zhang M, Yang D, Hossen M, Ding W, Fung K, Dominguez D, Bhattacharya R, Escobar-Hoyos L, Mukherjee P. Abstract C083: SMNDC1 alters the splicing of ERK to potentiate its activity in pancreatic cancer. Cancer Research 2024, 84: c083-c083. DOI: 10.1158/1538-7445.panca2023-c083.
- Altered RNA splicing a driver event in pancreatic cancerEscobar-Hoyos L. Altered RNA splicing a driver event in pancreatic cancer. Cancer Letters 2024, 581: 216543. DOI: 10.1016/j.canlet.2023.216543.
- Unsupervised Stain Decomposition via Inversion Regulation for Multiplex Immunohistochemistry Images.Abousamra S, Fassler D, Yao J, Gupta R, Kurc T, Escobar-Hoyos L, Samaras D, Shroyer K, Saltz J, Chen C. Unsupervised Stain Decomposition via Inversion Regulation for Multiplex Immunohistochemistry Images. Proceedings Of Machine Learning Research 2023, 227: 74-94. PMID: 38817539, PMCID: PMC11138139.