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Focused at the interface of engineering, neuroscience and medicine, our research seeks to develop clinical therapies for central nervous system (CNS) injury and disorders, including spinal cord injury, traumatic brain injury and glioma formation. Using biomaterial microenvironments and advanced imaging tools, we aim to identify differences between the extracellular environment of diseased and healthy or developing and adult CNS tissues and exploit these mechanistic discoveries to develop novel therapies that target the local environment. Engineered microenvironments enable ex vivo investigation of key physiological players within conditions that approximate those in vivo so that physiologically relevant data can be obtained in a simplified context. Ultimately, this approach enables the development of new therapeutic strategies based on controlled manipulation of these players. The long-term goal of this research is to translate biomaterial microenvironments to in vivo regenerative therapies using hydrogels, gene and protein delivery and cell replacement as building blocks. 1.Regenerative Strategies for Spinal Cord Injury Repair. This project aims to develop hydrogel-based microenvironments engineered to mimic the native, healthy spinal cord and promote functional regeneration of injured tissue. These microenvironments are designed to administer combinatorial therapies that address multiple barriers to spinal cord repair by incorporating guidance architecture, substrate-immobilized factors, genetically encoded regulatory factors, and cell replacement. 2.Quantitative, Dynamic and High-Throughput Analysis of Oligodendrocyte Differentiation in the Central Nervous System. A major factor contributing to the failure of repair after spinal cord injury is an inhibition of oligodendrocyte differentiation by the local, in vivo microenvironment. As the process of oligodendrocyte differentiation is not well understood, there is a need to identify the parameters required to direct oligodendrocyte differentiation. Performing high-throughput arrays to dynamically monitor intracellular signaling processes on multiple tissue scales (single cell and population) and functional levels (initial signaling pathway activation and protein expression) will dramatically enhance our understanding of the microenvironmental parameters required to effectively drive oligodendrocyte differentiation and will significantly augment our ability to design of biomaterial therapeutics mediate spinal cord repair. 3.Screening of Drug Targets for Treatmentof Glioblastoma Multiforme: Glioblastoma multiforme (GBM) is an extremely aggressive cancer that is typically unresponsive to currently available pharmacological agents. It has been hypothesized that the unique extracellular environment of the brain renders tumor cells unresponsive to chemotherapy. Using a library of library lentivirus-based reporters for transcription factor activity, we aim to identify intracellular signals that differ when GBM tumor cells or native glial cells are cultured in hydrogel microenvironments in which the chemical composition and mechanical stiffness can be finely tuned to mimic both the healthy and cancerous brain. The major goal of these studies is to identify key differences in the extracellular environment surrounding GBM that impart drug resistance with the goal of discovering develop novel, highly effective therapeutic agents.
研究兴趣
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Usha Nekanti, Pooja S. Sakthivel, Atena Zahedi,Dana A. Creasman,Rebecca A. Nishi,Courtney M. Dumont,Katja M. Piltti, Glenn L. Guardamondo, Norbert Hernandez, Xingyuan Chen, Hui Song,Xiaoxiao Lin,
npj Regenerative Medicineno. 1 (2024): 1-20
Nature Reviews Bioengineeringno. 12 (2023): 972-988
Soniya Bastola,Marat S. Pavlyukov,Yasmin Ghochani, Neel Sharma, Mayu A. Nakano,Sree Deepthi Muthukrishnan, Sang Yul Yu,Min Soo Kim,Alireza Sohrabi,Natalia P. Biscola,Daisuke Yamashita,Ksenia S. Anufrieva,
biorxiv(2023)
Gevick Safarians,Alireza Sohrabi, Itay Solomon,Weikun Xiao,Soniya Bastola,Bushra W. Rajput, Mary Epperson, Isabella Rosenzweig, Kelly Tamura, Breahna Singer,Joyce Huang,Mollie J. Harrison,
Zin Z. Khaing,Jessica Y. Chen,Gevick Safarians, Sohib Ezubeik, Nicolas Pedroncelli, Rebecca D. Duquette,Tobias Prasse,Stephanie K. Seidlits
Josh Karam, Breahna J Singer,Hiromi Miwa,Limin H Chen, Kajal Maran,Mahdi Hasani,Sarahi Garza,Bianca Onyekwere,Hsin-Chih Yeh,Song Li,Dino Di Carlo,Stephanie K Seidlits
TISSUE ENGINEERING PART A (2022): 14-14
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Weikun Xiao,Mahsa Pahlavanneshan,Chae-Young Eun,Xinyu Zhang,Charlene DeKalb,Bayan Mahgoub, Hanaa Knaneh-Monem, Sana Shah,Alireza Sohrabi,Stephanie K. Seidlits,Reginald Hill
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