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个人简介
Our research is based on developing clinically translatable models of both primary, recurrent and metastatic brain tumors, and cell based cell surface receptor therapeutics that simultaneously target cell death and proliferation pathways in an effort to eradicate brain tumors. We have engineered different stem cells types to release therapeutic proteins to specifically induce apoptosis in tumor cells and target different populations of immune cells in TME and tested them in primary and metastatic mouse tumor models. Our laboratory has also focused on targeting tumors that are resistant to different therapeutic drugs and oncolytic viruses. Resultantly, we have developed stem cell deliverable bi-modal therapeutic molecules and oncolytic herpes virus and shown their efficacy in mouse models of aggressive and invasive brain tumors. We have created different immunomodulatory stem cells to boost tumor resection induced CD4/8 T cells post-tumor debulking and shown therapeutic efficacy in different mouse tumor models.
Tumor cells hold promise as anti-cancer agents due to its ability to serve as the natural source of patient-specific neoantigens. To take advantage of this as therapeutics, we have recently CRISPR/Cas9 engineered self-targeting tumor cells to knock out cell surface receptors and release targeting ligands to kill the tumor cells. We have shown that re-purposed therapeutic tumor cells (ThTC) specifically home to tumor cells and release targeted ligands that induce tumor cell killing which translates into marked survival benefits in mouse models of primary and brain cancer. More recently, we have engineered tumor cells to release dual immunomodulatory agents and shown the potential of these ThTC to simultaneously kill tumor cells and induce immunological memory. Inherently linked to the brain tumor therapy paradigm are imaging techniques, thus we employ fluorescent/bioluminescent imaging markers and optical imaging techniques to track stem cells, image apoptosis and changes in tumor volumes in real time in vivo.
Tumor cells hold promise as anti-cancer agents due to its ability to serve as the natural source of patient-specific neoantigens. To take advantage of this as therapeutics, we have recently CRISPR/Cas9 engineered self-targeting tumor cells to knock out cell surface receptors and release targeting ligands to kill the tumor cells. We have shown that re-purposed therapeutic tumor cells (ThTC) specifically home to tumor cells and release targeted ligands that induce tumor cell killing which translates into marked survival benefits in mouse models of primary and brain cancer. More recently, we have engineered tumor cells to release dual immunomodulatory agents and shown the potential of these ThTC to simultaneously kill tumor cells and induce immunological memory. Inherently linked to the brain tumor therapy paradigm are imaging techniques, thus we employ fluorescent/bioluminescent imaging markers and optical imaging techniques to track stem cells, image apoptosis and changes in tumor volumes in real time in vivo.
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Pablo A. Valdes,Chih-Chieh (Jay) Yu, Jenna Aronson, Debarati Ghosh,Yongxin Zhao,Bobae An,Joshua D. Bernstock,Deepak Bhere,Michelle M. Felicella,Mariano S. Viapiano,Khalid Shah,E. Antonio Chiocca,
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STEM CELLS TRANSLATIONAL MEDICINE (2024)
Cancer Researchno. 6_Supplement (2024): 1419-1419
FRONTIERS IN IMMUNOLOGY (2024): 1324618-1324618
Priscilla Chan,Qiulian Wu,Anahit Hovsepyan,Seda Mkhitaryan, Gevorg Karapetyan,Khalid Shah,Hiroaki Wakimoto,Theodore Kamenecka, Laura A. Solt, Jamie Cope,Tsuyoshi Hirota,Rex A. Moats,
Cancer Researchno. 6_Supplement (2024): 669-669
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FRONTIERS IN NEUROSCIENCE (2023): 1184049-1184049
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