About

Sara Pedron Haba is a Research Assistant Professor in Biomedical and Translational Sciences at the Carle Illinois College of Medicine. She holds a PhD in Materials Science and Engineering from the Institute of Polymer Science and Technology at University Carlos III Madrid, and a BS in Chemistry from the University of Valencia. Her research focuses on the development of microphysiological systems to better recreate brain biology and function, aiming to address the complexity of the brain and the interactions between human genetics and environmental factors that contribute to brain diseases. Her work involves creating biomaterial-based platforms to study disease development and therapeutic approaches, with particular emphasis on brain disease microenvironments, materials and chemistry of responsive biomaterials, and mechanisms of tumor resistance. She has contributed to advancing the understanding of brain cancer, tumor microenvironments, and brain disease models through her research. Her efforts aim to improve the efficacy of treatments and patient quality of life by developing physiologically relevant platforms that mimic brain tissue and pathology.

Selected publications

• Biomimetic model for the identification of distinctive microenvironmental factors in glioblastoma radiosensitivity

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-15

  articleOpen accessSenior authorCorresponding

  Radiation therapy (RT) has long been included in the treatment of glioblastoma (GBM). However, radioresistance in cancer cells as well as toxicity in normal tissues are major obstacles to clinical efficacy. Improved understanding of the mechanisms of tumor microenvironment-induced radioresistance during and after radiation therapy can provide fundamental insights to improve clinical outcomes in GBM. Here, using three-dimensional engineered hydrogel models in vitro, we report the influence of extracellular matrix, hypoxia, and adjacent neuronal cells in radiotherapeutic sensitivity. We find that mechanical cues and oxygen availability regulate cellular response to radiation, with softer matrices allowing for more DNA damage. Hyaluronan fragments from the extracellular matrix also modulate rapid metabolic response to radiation, especially in hypoxic environments. We show that neuronal networks influence tumor metabolic activity and the inflammatory response. Overall, we demonstrate here that alternative radiation strategies, such as low dose rate radiation therapy and microenvironmental regulation, have the potential to be more effective in a specific subset of radiosensitive GBM tumors.

  PublisherOA PDFDOI

• Abstract 4272: Disruption of hyaluronan metabolism alters glioma cell proliferation by ligand dependent and independent mechanisms

  Cancer Research · 2024-03-22

  articleSenior author

  Abstract Hyaluronan (HA) is the main constituent of the brain extracellular matrix and is an essential component of the glioblastoma (GBM) tumor microenvironment. The biosynthesis and catabolism of hyaluronan has multiple roles in tissue architecture and cell signaling. Dysregulation of these mechanisms is crucial in pathological processes such as cancer, inflammation or tissue remodeling. The role of HA is believed to be strongly dependent on its size (molecular weight), location, and cell receptor density and activity. HA is produced intracellularly by HA synthases (HAS1-3) and can also be catabolized endogenously by hyaluronidases (HYAL1-3).The fabrication of controlled microenvironments provided by three dimensional (3D) models helps to elucidate the role of HA signaling in GBM tumors. We exploit here the advantages of these models to understand the role of hyaluronan in the local behavior of GBM after radiation therapy and selected targeted inhibitors. We have established engineered brain tumor biomaterials based on functionalized hydrogels to monitor the response of patient-derived xenograft cell populations with different molecular signatures in combination with microfluidic devices. We have analyzed shifts in metabolism, hyaluronan secretion, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We also show that HA fragments can enhance tumor metabolism and growth through ligand dependent and independent mechanisms. We provide bioengineered platforms and strategies to predict and stratify tumors in order to achieve more efficient combinatorial treatments targeting endogenous hyaluronan production. This work emphasizes the potential of these preclinical models to predict and accelerate cancer treatments, more relevant in malignancies with limited treatment options. Citation Format: Edward R. Neves, Joseph Mueller, Achal Anand, Kimberly Selting, Hui Xu, Roddel Remy, Brendan Harley, Sara Pedron-Haba. Disruption of hyaluronan metabolism alters glioma cell proliferation by ligand dependent and independent mechanisms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4272.

  PublisherDOI

• Abstract A045: Engineered systems for tumor modeling facilitate the assessment of theraputic interventions

  Cancer Research · 2024-03-04

  articleSenior author

  Abstract Brain cancers remain some of the most challenging tumors to treat. The goal of our research is to use a 3D in vitro model to acquire in-depth understanding of the unique environment of brain tumors in order to find new biomarkers of disease and develop more efficient therapeutic approaches. Glioblastomas (GBM) present a very poor prognosis, they exhibit high infiltration into brain parenchyma, impairing surgical resection and leading to recurrence. The recurrent tumor is predominantly more aggressive and resistant to available therapeutic strategies. Brain extracellular matrix (ECM) plays a key role in glioblastoma invasion and therapeutic resistance. In particular, the aberrant biosynthesis of the main component of brain ECM, hyaluronic acid (HA), has been associated to pathological conditions. We investigate the influence of tumor extracellular microenvironment in glioblastoma progression. We focus on the tumor-associated HA biosynthesis in response to biophysical alterations, such as hypoxia and stiffness, and after radio and chemotherapeutic interventions. The ability to manipulate tumor ECM can improve therapeutic outcomes and restrict glioblastoma growth and infiltration. Citation Format: Joseph Mueller, Ryan Yao, Kim Selting, Catherine Best-Popescu, Brendan Harley, Sara Pedron-Haba. Engineered systems for tumor modeling facilitate the assessment of theraputic interventions [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A045.

  PublisherDOI

• Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-08 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. We aim here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. We use tissue engineering approaches to recreate the three-dimensional tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived xenograft GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We propose a tumor specific combination treatment of HYAL and HAS inhibitors to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand - dependent signaling roles of hyaluronan in glioblastoma. Significance: The control of aberrant hyaluronan metabolism in the tumor microenvironment can improve the efficacy of current treatments. Bioengineered preclinical models demonstrate potential to predict, stratify and accelerate the development of cancer treatments.

  PublisherOA PDFDOI

• Abstract 1191: Targeting the tumor extracellular matrix to enhance therapeutic interventions in glioblastoma

  Cancer Research · 2023-04-04

  articleSenior author

  Abstract Brain cancers remain some of the most challenging tumors to treat. The goal of our research is to use a 3D in vitro model to acquire in-depth understanding on the unique environment of brain tumors in order to find new biomarkers of disease and develop more efficient therapeutic approaches. Brain extracellular matrix (ECM) plays a key role in glioblastoma invasion and therapeutic resistance. In particular, the aberrant biosynthesis of the main component of brain ECM, hyaluronic acid (HA), has been associated to pathological conditions. In this study, we investigate the influence of tumor extracellular microenvironment in glioblastoma progression. We focus here on the tumor-associated HA biosynthesis in response to biophysical alterations, such as hypoxia and stiffness, and after radio and chemotherapeutic interventions. The ability to manipulate tumor ECM can improve therapeutic outcomes and restrict glioblastoma growth and infiltration. We have established engineered brain tumor biomaterials based on functionalized gelatin hydrogels decorated with covalently bound HA. This biomaterial approach can monitor the response of patient-derived xenograft cell populations with different molecular signatures (1, 2) in combination with microfluidic devices. Here, we characterized tumor cell response to targeted inhibitors and ionizing radiation. We quantified HA molecular weight (MW) distribution of secreted HA, and the tumor cell response to inhibition of HA synthase 2 (HAS2) and hyaluronidase (Hyal). Analysis of HA biosynthesis suggests that GBM cells compensate for a lack of matrix-bound HA by producing soluble HA to stimulate invasion. Moreover, we revealed that different signaling pathways are altered in the tumor cells depending on the microenvironment as they respond to an EGFR and CD44 inhibitor. While the decrease in invasion and proliferation in gelatin-only matrices comes from the negative regulation of ERK pathway, HA plays a favorable role in the inhibition of EGFR, through STAT3 deactivation (3). The MW and abundance of HA are mediated by the activity of HA synthases and hyaluronidases. These enzymes vary in expression, rate, and MW of the HA produced. We have found a heterogeneous profile of MW distributions secreted by different tumor types when exposed to different targeted inhibitors. We have also shown an increase in HA secretion after exposure to radiation and inhibition of hyaluronidase, also associated to significant changes in cell proliferation. The oxidative stress induced by the hypoxic environment also induces the production of hyaluronic acid and significantly affects glycolysis and mitochondrial oxidative phosphorylation, that are further altered by the molecular weight of the HA present in the extracellular space. (1) Pedron S. Adv. Healthcare Mater. 2017; 6:1700529; (2) Pedron S. MRS Commun. 2017; 7:442-449; (3) Pedron S. Biomaterials 2019; 219:119371. Citation Format: Edward R. Neves, Joseph Mueller, Achal Anand, Kimberly A. Selting, Brendan A. Harley, Sara Pedron-Haba. Targeting the tumor extracellular matrix to enhance therapeutic interventions in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1191.

  PublisherDOI

Labs

• Sara Pedron Haba Research GroupPI

Awards & honors

• NextGen Star, American Association for Cancer Research (2021…
• Nature Publishing Award, Society for Biomaterials (2016)
• CPLC 10K Pilot Program, Center for the Physics of Living Cel…
• Doctorate Extraordinary Award, University Carlos III Madrid…