Project Description:

Cancer is a major threat for humans worldwide, and unsatisfactory cure rates of common cancer treatments, including chemotherapy and radiotherapy, require new therapeutic approaches. Recently, adoptive cellular immunotherapies with chimeric antigen receptor (CAR) engineered T and natural killer (NK) cells have shown impressive clinical responses in patients with various blood and solid cancers. However, current clinical practices are limited by the need of large numbers of healthy cells, resistance to gene editing, lack of in vivo persistence, and a burdensome manufacturing strategy that requires donor cell extraction, modulation, expansion, and re-introduction per each patient. The ability to generate universally histocompatible and genetically-enhanced immune cells from renewable human pluripotent stem cell (hPSC) lines offers the potential to develop an off-the-shelf cellular immunotherapy. While functional CAR-T and NK cells have been successfully derived from hPSCs, a significant gap remains in the scalability, time-consuming (>7 weeks), purity and robustness of differentiation methods due to the cumbersome use of serum and/or feeder cells, which will incur potential risk for contamination and may cause batch-dependency. To address these challenges, this project aims to engineer hPSCs with synthetic CARs and develop novel platforms for scalable production of functional CAR-T, CAR-NK cells and CAR-neutrophils for targeted immunotherapy.

Start Date:

01/01/2023 to 08/01/2023

Postdoc Qualifications:

Eligible candidates should or will hold a Ph.D. in bioengineering or life science, or a related discipline before the starting date (negotiable) of the post-doc position. Previous experience with stem cells, biomaterials, genome editing, bioinformatics, immunoengineering, cancer biology or animal models is a plus, though not required.

Co-Advisors:

Xiaoping Bao, bao61@purdue.edu, Davidson School of Chemical Engineering, https://sites.google.com/view/xiaoping-bao/home;
Qing Deng, qingdeng@purdue.edu, Department of Biological Sciences, https://www.bio.purdue.edu/lab/deng/

Bibliography:

1. Jung J, Chang Y, Jin G, Lian X, Bao X. Temporal Expression of Transcription Factor ID2 Improves Natural Killer Cell Differentiation from Human Pluripotent Stem Cells. ACS Synth. Biol. doi.org/10.1021/acssynbio.2c00017 (2022).
2. Hsu AY, Wang D, et al. Phenotypical microRNA screen reveals a noncanonical role of CDK2 in regulating neutrophil migration. Proc Natl Acad Sci USA, 116 (37): 18561-18570 (2019).
3. Chang Y, Syahirah R, Oprescu SN, Wang X, Jung J, Cooper SH, Torregrosa-Allen S, Elzey BD, Hsu AY, Randolph LN, Sun Y, Kuang S, Broxmeyer HE, Deng Q, Lian X, Bao X. Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells. Biomaterials. 285, 121569 (2022).
4. Zhou W, Pal AS, et al. MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation. Cell Rep, 22 (7): 1810-1823 (2018).
5. Bao X, et al. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat Biomed Eng, 1: 0003 (2016).