Lijie Shi, Ph.D.

Congenital cardiovascular disease is one of main clinical features both for rare diseases of 22q11.2 deletion syndrome (22q11.2 DS) and Miller-Dieker syndrome. The 22q11.2 DS is the most common human chromosomal deletion syndrome, occurring in approximate 1:4000 live births. Miller-Dieker syndrome is another type of rare disease with prevalence of approximate 1:100000 live births. CRKL and CRK, which encodes same signaling adaptor proteins, are two candidate genes responsible for the cardiovascular diseases for 22q11.2 DS and Miller-Dieker syndrome, respectively. One big gap in the field is that it is unclear how loss of Crk/Crkl cause cardiovascular diseases, and my main projects aiming to understand in which cell types those two genes function and to investigate the underlying molecular mechanism for the caused defects by using genetically modified mouse models.

1. Shi L, Racedo SE, Diacou A, Park T, Zhou B, Morrow BE. Crk and Crkl have shared functions in neural crest cells for cardiac outflow tract septation and vascular smooth muscle differentiation. Hum Mol Genet. 2022 Apr 22;31(8):1197-1215. doi: 10.1093/hmg/ddab313. PMID: 34686881; PMCID: PMC9029238.
2. Shi L*, Song H, Zhou B, Morrow BE*. Crk/Crkl regulates early angiogenesis in mouse embryos by accelerating endothelial cell maturation. bioRxiv [Preprint]. 2023 Jul 13:2023.07.12.548782. doi: 10.1101/2023.07.12.548782. PMID: 37503032; PMCID: PMC10369973. (*co-corresponding authors)
3. Racedo SE, Liu Y, Shi L, Zheng D, Morrow BE. Dgcr8 functions in the secondary heart field for outflow tract and right ventricle development in mammals. Dev Biol. 2024 Feb;506:72-84. doi: 10.1016/j.ydbio.2023.12.005. Epub 2023 Dec 17. PMID: 38110169; PMCID: PMC10793380.
4. Wu B, Wu B, Benkaci S, Shi L, Lu P, Park T, Morrow BE, Wang Y, Zhou B. Crk and Crkl Are Required in the Endocardial Lineage for Heart Valve Development. J Am Heart Assoc. 2023 Sep 19;12(18):e029683. doi: 10.1161/JAHA.123.029683. Epub 2023 Sep 13. PMID: 37702066; PMCID: PMC10547300.
5. Zhao Y, Wang Y, Shi L, McDonald-McGinn DM, Crowley TB, McGinn DE, Tran OT, Miller D, Lin JR, Zackai E, Johnston HR, Chow EWC, Vorstman JAS, Vingerhoets C, van Amelsvoort T, Gothelf D, Swillen A, Breckpot J, Vermeesch JR, Eliez S, Schneider M, van den Bree MBM, Owen MJ, Kates WR, Repetto GM, Shashi V, Schoch K, Bearden CE, Digilio MC, Unolt M, Putotto C, Marino B, Pontillo M, Armando M, Vicari S, Angkustsiri K, Campbell L, Busa T, Heine-Suñer D, Murphy KC, Murphy D, García-Miñaúr S, Fernández L; International 22q11.2 Brain and Behavior Consortium (IBBC); Zhang ZD, Goldmuntz E, Gur RE, Emanuel BS, Zheng D, Marshall CR, Bassett AS, Wang T, Morrow BE. Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS. NPJ Genom Med. 2023 Jul 18;8(1):17. doi: 10.1038/s41525-023-00363-y. PMID: 37463940; PMCID: PMC10354062.