Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), represent a potentially inexhaustible supply of human cells for regenerative medicine, due to their ability of self-renewal and the capacity to differentiate into specialized cell types. In order to realize their full therapeutic potential, a number of challenges need to be overcome. One of the most important prerequisites is to be able to generate, under defined conditions, adequate numbers of the target cell type at sufficient purity and with the appropriate cellular functions.

The major research interest in the Bao lab is to use innovative technologies to engineer stem cells as models of human development and disease, as well to develop cellular and molecular therapies as next-generation of medicine for degenerative diseases, including neurological disorders, heart diseases, β cells for diabetes, T cells for cancers, et al. Our specific interests include:

Stem cell differentiation and biomanufacturing

Live cells are promising drugs for degenerative diseases, yet it remains challenge to generate and manufacture pure target cells from human pluripotent stem cells. We aim to develop new protocols and insights into cardiac cells for heart diseases, hematopoietic stem cells for blood disorders, and immune T, neutrophils, and natural killer (NK) cells for cancer immunotherapy.

Human disease modeling and gene editing

Gene therapy holds great promise to treat a number of inherited genetic disorders, including leukemia, Duchenne Muscular Dystrophy (DMD) et al. We are combining biomaterials, CRISPR/Cas9-based genome editing and adeno-associated virus (AAV)-mediated gene delivery to generate diseased organoids and to develop novel gene therapies.

Bioinformatives and computational biology

We aspire to develop and use statistical and computational methods to better understand gene evolution and function during human development and diseases. In particular, we are interested to analyze the high-throughput sequencing data and investigate the functions of the long non-coding RNAs (lncRNAs) during heart development and disease.

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PubMed

Lu Y, Varghese A, Nahar R, Chen H, Shao K, Bao X*, Li C*. scChat: A Large Language Model-Powered Co-Pilot for Contextualized Single-Cell RNA Sequencing Analysis. bioRxiv doi.org/10.1101/2024.10.01.616063 (2024). 

Chang Y, Jin G, Luo W, Luo Q, Jung J, Hummel SN, Torregrosa-Allen S, Elzey BD, Low PS*, Lian X*, Bao X*. Engineered human pluripotent stem cell-derived natural killer cells with PD-L1 responsive immunological memory for enhanced immunotherapeutic efficacy. Bioact Mater 27: 168-180 (2023). https://www.sciencedirect.com/science/article/pii/S2452199X23001123.   

Chang Y, Cai X, Syahirah R, Yao Y, Xu Y, Jin G, Bhute VJ, Torregrosa-Allen S, Elzey BD, Won Y-Y, Deng Q, Lian XL*, Wang X*, Eniola-Adefeso O*, Bao X*. CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy. Nat Commun 14(1): 2266 (2023). https://www.nature.com/articles/s41467-023-37872-4. 

Chang Y, Deng Q, Bao X*. A pluripotent road to immunoengineering. Nat Rev Bioeng (2023). www.nature.com/articles/s44222-023-00056-2.

Bao X, Lian X, Hacker TA, Schmuck EG, Qian T, Bhute VJ, Han T, Shi M, Drowley L, Plowright A, Wang QD, Goumans MJ, Palecek SP. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat Biomed Eng. 2016 1; doi: 10.1038/s41551-016-0003.

Lian X, Bao X, Zilberter M, Westman M, Fisahn A, Hsiao C, Hazeltine LB, Dunn KK, Kamp TJ, Palecek SP. Chemically defined, albumin-free human cardiomyocyte generation. Nat Methods. 2015 Jul:12(7): 595-6. doi: 10.1038/nmeth.3448.

"Methods for epicardial differentiation of human pluripotent stem cells", Palecek SP, Bao X, Lian X., US Patent, US10131878B2 (2018).

"Chemically defined albumin-free conditions for cardiomyocyte differentiation of human pluripotent stem cells", Palecek SP, Lian X, Bao X., US Patent, US9765299 B2 (2017).

"Simplified methods for generating endothelial cells from human pluripotent stem cells under defined conditions:, Palecek SP, Lian X, Bao X., US Patent, US9290741 B2 (2016).

"Generating aorta-gonad-mesonephros-like hematopoietic cells from human pluripotent stem cells under a defined condition" Bao X, Chang Y. US Patent App. 17/800,320 (2023).