Engineer and manufacture off-the-shelf CAR-T and NK cells from human stem cells for immunotherapy
Interdisciplinary Areas: | Engineering-Medicine |
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Project Description
Cancer is a major cause of death in US, with over 0.6 million cancer-related deaths in 2019. While treatments like chemotherapy, radiation and surgery are available to remove the cancer, the cure rates are unsatisfactory, particularly for refractory cancers, requiring new therapeutic approaches. Adoptive cellular immunotherapies with T and natural killer (NK) cells have provided new alternatives to fight cancer. Despite their significant potential, immune cell-based therapies suffer from several major drawbacks: challenge in obtaining sufficient healthy immune cells, resistance to genome editing, and suboptimal cytotoxicity against solid tumor. Thus, the ability to easily generate large numbers of functional immune cells and ease of genome editing enable the continuously renewing human pluripotent stem cells (hPSCs) as a promising source to develop a truly off-the-shelf immunotherapy. This project aims to engineer hPSCs with cancer-targeted chimeric antigen receptors (CARs) for massive production of CAR-T or NK cells, and investigate their functions in treating solid cancers, including prostate and brain cancers.
Start Date
04/01/021
Postdoc Qualifications
A PhD degree majored in bioengineering, biology, immunology, or related engineering/biology field is required before the project starts;
Previous research experiences in stem cells, immunology, and/or animal models is not required, but preferred for the project.
Co-Advisors
Xiaoping Bao, bao61@purdue.edu, Davidson School of Chemical Engineering, https://engineering.purdue.edu/ChE/people/ptProfile?resource_id=210038;
Chang-Deng Hu, hu1@purdue.edu, Department of Medicinal Chemistry and Moleculary Pharmacology, https://www.changdenghulab.com/chang-deng-hu;
Qing Deng, qingdeng@purdue.edu, Department of Biological Sciences, https://www.bio.purdue.edu/lab/deng/
References
Bao X, et al. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat. Biomed. Eng. 2016.
Hsu A, et al. Phenotypical microRNA screen reveals a noncanonical role of CDK2 in regulating neutrophil migration. PNAS. 2019.
Jeffries J, et al. miRNA-223 at the crossroads of inflammation and cancer. Cancer Letter. 2019.
Owens, J. PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes. iScience. 2019.
Deng, X. Protein arginin methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth. Oncogene. 2017