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Escobar-Hoyos Lab


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 recelty 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.

Research Interests:

  • Pancreatic ductal adenocarcinoma,
  • lung adenocarcinoma,
  • neuroendocrine tumors,
  • RNA splicing,
  • cancer biology,
  • tumor immunology,
  • genetically engineered mouse models,
  • KRAS,
  • GTPases,
  • driver mutations,
  • p53, and
  • resistance to therapy.

Lab Members

  • Luisa Escobar-Hoyos

    Principal Investigator

    Assistant Professor of Therapeutic Radiology

    Dr. Escobar-Hoyos obtained her master’s degree in Biomedical Sciences at the Universidad del Valle in Cali, Colombia. As a Fulbright Scholar, she pursued a Ph.D. in Cancer Molecular and Cellular Pharmacology at Stony Brook University mentored by Dr. Kenneth Shroyer. She then completed her postdoctoral training at the Memorial Sloan Kettering Cancer Center co-mentored by Drs. Steven Leach and Omar Abdel-Wahab. In 2020, Dr. Escobar-Hoyos joined the Department of Therapeutic Radiology at Yale as an Assistant Professor.

    The overarching goal of Dr. Escobar-Hoyos' lab is to cure pancreatic and lung cancers. Specifically, the team seeks to understand and target somatic mutations, and aberrant RNA processing in these tumors to  develop of novel therapies. 

  • Diana Martínez Saucedo

    Postdoctoral Associate

    As a scientist my goal is to develop novel therapies for pancreatic cancer by understanding how alternative RNA splicing drives pathogenesis, anti-tumor immunological functions, and serves as a potential therapeutic target.

    My background spans over 10 years of training as a molecular immunologist. My research projects aimed to elucidate how helminth derived molecules induce anti-inflammatory M2 macrophages that attenuate inflammation. My doctoral work led to the discovery that helminth-derived molecules reduced the expression of inflammatory mediators and induced microRNAs associated with the M2 macrophages. This finding suggests that reprogramming macrophages through the identified pathways can guide the development of new therapies across inflammatory pathologies where M2 macrophages contribute to disease progression.

    Thus, with my understanding of the impact that post-transcriptional events have in cells, I became motivated to study the role of alternative RNA splicing in one of the most aggressive and therapeutically resistant cancers: Pancreatic cancer. Understanding the microenvironment of the tumors, tumor cell interaction with the immune system, and the role of RNA splicing in these contexts is crucial to develop better therapeutic approaches.

    Postdoctoral Fellowship: Leslie Warner, Yale Cancer Center.

  • Natasha Pinto Medici

    Postdoctoral Associate

    I am a microbiologist/immunologist with background in host-pathogen interactions and in molecular immunology that spans over 10 years of training. My doctoral work led to the discovery of how virulence factors activate inflammation responses in macrophages, and these findings impact our understanding of how we can develop therapeutics suitable for auto-immune diseases. With my thorough understanding that the immune system is a principal site that determines disease prognosis, I became motivated to pursue the study of its molecular regulation in pancreatic cancer, based on its high resistant to the best standard-of-care therapeutics we have and very short survival. In addition, while immunotherapy has shown promise in many cancers, pancreatic cancer is refractory to the current best immunotherapies available, suggesting that additional work is required to understand what makes the immune system in pancreatic cancer different and whether these differences can reveal therapeutic opportunities. 

  • Ryan Kawalerski
    Ryan is a 2nd year MSTP student at the Johns Hopkins University School of Medicine. He received his BS in Applied Math & Statistics and Biochemistry from SUNY Stony Brook. He is working with us to understand the alternative splicing phenotypes of driver mutations in pancreatic cancers, and is most interested in computational and molecular approaches for accurately quantifying and predicting genetic events.