3D bioprinting of biomimetic acute myeloid leukemia disease models

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Project Description

Acute Myeloid Leukemia (AML) is a hematological malignancy of bone marrow (BM) origin characterized by the clonal expansion and differentiation arrest of myeloid progenitor cells. Worldwide the incidence of AML has been steadily increasing over the last three decades. AML remains a therapeutic challenge due to its high heterogeneity, with various subclones possessing distinct genetic and epigenetic alterations contributing to tumor functional differences such as drug resistance. We have developed a unique class of ultrashort self-assembling peptide hydrogels and proven in previous studies the potential use of these biomaterials as a 3D culture system for various cell types. This study aims to develop a 3D AML "organoid" model using advanced self-assembling peptides and patient-derived cellular components: primarily, establishing a model that closely recapitulates the tumor microenvironment and can be used in drug screening applications to enable personalized medicine therapeutics; ultimately, providing a platform that can help in answering unresolved questions regarding tumor development and niche organization.
Program - BioEngineering
Division - Biological and Environmental Sciences and Engineering
Field of Study - blood cancer, tissue engineering, nanomedicine, materials science

About the
Researcher

Charlotte A. E. Hauser

Professor, Bioengineering <br/>Chair, Bioengineering Program

Charlotte A. E. Hauser
Professor Hauser’s research interests align at the interfaces between chemistry, biomedicine, bioengineering and nanotechnology. Focus is on the development of platform technologies, using smart nanomaterials for regenerative, biomedical and environmental applications.

Her interest refers to the rational molecular design, synthesis and mechanistic understanding of novel supramolecular structures. Investigated systems include peptide-based nanostructures with an innate propensity to self-assemble to biomimetic architectures applicable for biomedical applications such as cell substrates, sensors and 3D tissue scaffolds for regenerative medicine. Bottom-up nanofabrication is a powerful tool for the development of functional tissue equivalents, organotypic tissues and devices. Moreover, these biomimetic supramolecular constructs will be used for the design and fabrication of novel organ-on-a-chip devices and disease models.

Furthermore, Professor Hauser is interested in 3D bioprinting, using supramolecular organotypic constructs to fabricate high-throughput platforms for drug screening, pathogen detection and other diagnostic purposes. Synthetic biology approaches are explored for the generation of functional biomaterial.

Desired Project Deliverables

1. Identification and formulation of self-assembling peptide for the fabrication of 3D biomimicry models representative of the leukemic bone marrow niche i. Design and synthesis of suitable peptides and functionalization with bioactive moieties ii. Cytocompatibility testing of peptide hydrogel scaffolds iii. Establishment of 3D AML in vitro culture models 2. Investigation of leukemia microenvironment role on disease development and progression i. Investigation of exosomes role in tumor microenvironment regulation ii. Investigation of stromal cells role in tumor microenvironment regulation 3. Evaluation (Validation) of the 3D AML models as an in vitro model for drug screening i. Assessment of the effectiveness of the developed 3D biomimicry AML models in drug screening ii. Gene expression analysis and biomarkers identification

RECOMMENDED STUDENT ACADEMIC & RESEARCH BACKGROUND

Biology
Biology
Cancer biology
Cancer biology
Nanomedicine
Nanomedicine