About CAMTraST: Advancing Disease Research
In November 2012, the University of Michigan launched the Center for Advanced Models for Translational Sciences and Therapeutics (CAMTraST). The long-term goal of the Center is to stimulate bench-to-bedside research that sheds light on molecular mechanisms underlying the development and progression of diseases. Discoveries from innovative and multi-disciplinary projects will reveal novel and effective intervention strategies to prevent and treat diseases.
We have assembled a team of talents in molecular biology, embryology, and animal reproduction. Our team members are among the first in the world to establish rabbit embryonic stem cell lines, to generate cloned rabbits, and to produce knockout (KO) pigs. Recently, we have made several breakthroughs in gene targeting in rabbits.
- Graham SE, Clarke SL, Wu KH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, … Willer CJ. The power of genetic diversity in genome-wide association studies of lipids. Nature. 2021 Dec 9. doi: 10.1038/s41586-021-04064-3. Epub ahead of print. PMID: 34887591.
- Zhou D, Feng H, Yang Y, Huang T, Qiu P, Zhang C, Olsen TR, Zhang J, Chen YE, Mizrak D, Yang B. hiPSC Modeling of Lineage-Specific Smooth Muscle Cell Defects Caused by TGFBR1A230T Variant, and Its Therapeutic Implications for Loeys-Dietz Syndrome. Circulation. 2021 Oct 5;144(14):1145-1159. doi: 10.1161/CIRCULATIONAHA.121.054744. Epub 2021 Aug 4. PMID: 34346740; PMCID: PMC8681699.
- Koike T, Koike Y, Yang D, Guo Y, Rom O, Song J, Xu J, Chen Y, Wang Y, Zhu T, Garcia-Barrio MT, Fan J, Chen YE, Zhang J. Human apolipoprotein A-II reduces atherosclerosis in knock-in rabbits. Atherosclerosis. 2021 Jan;316:32-40. doi: 10.1016/j.atherosclerosis.2020.11.028. Epub 2020 Nov 28. PMID: 33296791; PMCID: PMC7770079.
- Bai Y, Lin W, Xu J, Song J, Yang D, Chen YE, Li L, Li Y, Wang Z, Zhang J. Improving the genome assembly of rabbits with long-read sequencing. Genomics. 2021 Sep;113(5):3216-3223. doi: 10.1016/j.ygeno.2021.05.031. Epub 2021 May 27. PMID: 34051323.
- Liu Y, Zhao Y, Shukha Y, Lu H, Wang L, Liu Z, Liu C, Zhao Y, Wang H, Zhao G, Liang W, Fan Y, Chang L, Yurdagul A Jr, Pattillo CB, Orr AW, Aviram M, Wen B, Garcia-Barrio MT, Zhang J, Liu W, Sun D, Hayek T, Chen YE, Rom O. Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis. Cell Rep. 2021 Jul 27;36(4):109420. doi: 10.1016/j.celrep.2021.109420. PMID: 34320345; PMCID: PMC8363062.
- Navarro RS, Jiang L, Ouyang Y, Luo J, Liu Z, Yang Y, Qiu P, Kuroda K, Chen YE, Ma PX, Yang B. Biomimetic tubular scaffold with heparin conjugation for rapid degradation in in situ regeneration of a small diameter neoartery. Biomaterials. 2021 Jul;274:120874. doi: 10.1016/j.biomaterials.2021.120874. Epub 2021 May 12. PMID: 34051629; PMCID: PMC8390125.
- Chen YE. Translating Cardiovascular Genomics to Clinical Practice. Cardiovasc Drugs Ther. 2021 Jun;35(3):613-615. doi: 10.1007/s10557-021-07177-z. Epub 2021 Apr 14. PMID: 33852094; PMCID: PMC8196632.
- Song J, Hoenerhoff M, Yang D, Yang Y, Deng C, Wen L, Ma L, Pallas B, Zhao C, Koike Y, Koike T, Lester P, Yang B, Zhang J, Chen YE, Xu J. Development of the Nude Rabbit Model. Stem Cell Reports. 2021 Mar 9;16(3):656-665. doi: 10.1016/j.stemcr.2021.01.010. Epub 2021 Feb 18. PMID: 33606990; PMCID: PMC7940256.
- Wang H, Guo Y, Lu H, Luo Y, Hu W, Liang W, Garcia-Barrio MT, Chang L, Schwendeman A, Zhang J, Chen YE. Krüppel-Like Factor 14 Deletion In Myeloid Cells Accelerates Atherosclerotic Lesion Development. Cardiovasc Res. 2021 Feb 4:cvab027. doi: 10.1093/cvr/cvab027. Epub ahead of print. PMID: 33538785.
- Fan J, Wang Y, Chen YE. Genetically Modified Rabbits for Cardiovascular Research. Front Genet. 2021 Feb 2;12:614379. doi: 10.3389/fgene.2021.614379. PMID: 33603774; PMCID: PMC7885269.
- Yan H, Niimi M, Wang C, Chen Y, Zhou H, Matsuhisa F, Nishijima K, Kitajima S, Zhang B, Yokomichi H, Nakajima K, Murakami M, Zhang J, Chen YE, Fan J. Endothelial Lipase Exerts its Anti-Atherogenic Effect through Increased Catabolism of β-VLDLs. J Atheroscler Thromb. 2021 Feb 1;28(2):157-168. doi: 10.5551/jat.55244. Epub 2020 May 23. PMID: 32448826; PMCID: PMC7957034.
- Xu J, Zhang J, Yang D, Song J, Pallas B, Zhang C, Hu J, Peng X, Christensen ND, Han R, Chen YE. Gene Editing in Rabbits: Unique Opportunities for Translational Biomedical Research. Front Genet. 2021 Jan 28;12:642444. doi: 10.3389/fgene.2021.642444. PMID: 33584832; PMCID: PMC7876448. Yang D, Liang X, Pallas B, Hoenerhoff M, Ren Z, Han R, Zhang J, Chen YE, Jin JP, Sun F, Xu J. Production of CFTR-ΔF508 Rabbits. Front Genet. 2021 Jan 22;11:627666. doi: 10.3389/fgene.2020.627666. PMID: 33552140; PMCID: PMC7862758.
- Xu J, Livraghi-Butrico A, Hou X, Rajagopalan C, Zhang J, Song J, Jiang H, Wei HG, Wang H, Bouhamdan M, Ruan J, Yang D, Qiu Y, Xie Y, Barrett R, McClellan S, Mou H, Wu Q, Chen X, Rogers TD, Wilkinson KJ, Gilmore RC, Esther CR Jr, Zaman K, Liang X, Sobolic M, Hazlett L, Zhang K, Frizzell RA, Gentzsch M, O'Neal WK, Grubb BR, Chen YE, Boucher RC, Sun F. Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene. JCI Insight. 2021 Jan 11;6(1):e139813. doi: 10.1172/jci.insight.139813. PMID: 33232302; PMCID: PMC7821608.
- Yuan W, Yu B, Yu M, Kuai R, Morin EE, Wang H, Hu D, Zhang J, Moon JJ, Chen YE, Guo Y, Schwendeman A. Synthetic high-density lipoproteins delivering liver X receptor agonist prevent atherogenesis by enhancing reverse cholesterol transport. J Control Release. 2021 Jan 10;329:361-371. doi: 10.1016/j.jconrel.2020.11.016. Epub 2020 Nov 11. PMID: 33188828.
- Zhou J, Ren Z, Xu J, Zhang J and Chen YE: Gene editing therapy ready for cardiovascular diseases: opportunities, challenges, and perspectives. Medical Review Published online on October 21, 2021. https://doi.org/10.1515/mr-2021-0010
- Hiroyuki Hirai H, Liang X, Sun Y. Zhang Y, Zhang J, Chen YE, Mou H, Zhao YY, Xu J: The sodium/glucose cotransporters as potential therapeutic targets for CF lung diseases revealed by human lung organoid swelling assay. Molecular Therapy – Methods & Clinical Development. Published on November 24, 2021.
- Song J, Zhang J, Xu J, Garcia-Barrio M, Chen YE, Yang D. Genome engineering technologies in rabbits JBR, gene editing rabbits. J Biomed Res. 2020 Jun 12;35(2):135-147. doi: 10.7555/JBR.34.20190133. PMID: 32934190
- Ma L, Ruan J, Song J, Wen L, Yang D, Zhao J, Xia X, Chen YE, Zhang J, Xu J*. MiCas9 increases large size gene knock-in rates and reduces undesirable on-target and off-target indel edits. Nat Commun. 2020 Nov 27;11(1):6082. doi: 10.1038/s41467-020-19842-2. PMID: 33247137
- Song, J, Pallas, B, Yang, D, Zhang, J, Agarwal, Y, Chen, YE, Bility, M, Xu, J*. Immunodeficient Rabbit Models: History, Current Status and Future Perspectives. Appl. Sci. 2020, 10, 7369. https://doi.org/10.3390/app10207369
- Ruan J, Hirai H, Yang D, Ma L, Hou X, Jiang H, Wei H, Rajagopalan C, Mou H, Wang GS, Zhang JF, Li K, Chen YE, Sun F, Xu J*. Efficient gene editing at major CFTR mutation loci. Molecular Therapy: Nucleic Acids. 2019: 16:73-81. PMID: 30852378.
- Jiao J, Tian W, Qiu P, Norton EL, Wang MM, Chen YE, Yang B. Induced pluripotent stem cells with NOTCH1 gene mutation show impaired differentiation into smooth muscle and endothelial cells: Implications for bicuspid aortic valve-related aortopathy. J Thorac Cardiovasc Surg. 2018 Mar 12. pii: S0022-5223(18)30714-1. doi: 10.1016/j.jtcvs.2018.02.087.
- Li S, Chang Z, Zhu T, Villacorta L, Li Y, Freeman BA, Chen YE, Zhang J. Transcriptomic sequencing reveals diverse adaptive gene expression responses of human vascular smooth muscle cells to nitro-conjugated linoleic acid. Physiol Genomics. 2018 Apr 1;50(4):287-295. doi: 10.1152/physiolgenomics.00090.2017.
- Fan Y, Lu H, Liang W, Garcia-Barrio MT, Guo Y, Zhang J, Zhu T, Hao Y, Zhang J, Chen YE. Endothelial TFEB (Transcription Factor EB) Positively Regulates Postischemic Angiogenesis. Circ Res. 2018 Mar 30;122(7):945-957. doi: 10.1161/CIRCRESAHA.118.312672.
- Villacorta L, Minarrieta L, Salvatore SR, Khoo NK, Rom O, Gao Z, Berman RC, Jobbagy S, Li L, Woodcock SR, Chen YE, Freeman BA, Ferreira AM, Schopfer FJ, Vitturi DA. In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. Redox Biol. 2018 May;15:522-531. doi: 10.1016/j.redox.2018.01.005. Epub 2018 Jan 12.
- Chang L, Xiong W, Zhao X, Fan Y, Guo Y, Garcia-Barrio M, Zhang J, Jiang Z, Lin JD, Chen YE. Bmal1 in Perivascular Adipose Tissue Regulates Resting Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen. Circulation. 2018 Jan 25. pii: CIRCULATIONAHA.117.029972. doi: 10.1161/CIRCULATIONAHA.117.029972.
- Fan Y, Lu H, Liang W, Hu W, Zhang J, Chen YE. Krüppel-like factors and vascular wall homeostasis. J Mol Cell Biol. 2017 Oct 1;9(5):352-363. doi: 10.1093/jmcb/mjx037.
- Song J, Wang G, Hoenerhoff MJ, Ruan J, Yang D, Zhang J, Yang J, Lester PA, Sigler R, Bradley M, Eckley S, Cornelius K, Chen K, Kolls JK, Peng L, Ma L, Chen YE, Sun F, Xu J. Bacterial and Pneumocystis Infections in the Lungs of Gene-Knockout Rabbits with Severe Combined Immunodeficiency. Front Immunol. 2018 Mar 9;9:429. doi: 10.3389/fimmu.2018.00429. eCollection 2018.
- Song J, Yang D, Ruan J, Zhang J, Chen YE, Xu J. Production of immunodeficient rabbits by multiplex embryo transfer and multiplex gene targeting. Sci Rep. 2017 Sep 22;7(1):12202. doi: 10.1038/s41598-017-12201-0.
- Savastano LE, Zhou Q, Smith A, Vega K, Murga-Zamalloa C, Gordon D, McHugh J, Zhao L, Wang M, Pandey A, Thompson BG, Xu J, Zhang J, Chen YE, Seibel EJ, Wang TD. Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis. Nat Biomed Eng. 2017;1. pii: 0023. doi: 10.1038/s41551-016-0023. Epub 2017 Feb 10. PubMed PMID: 28555172; PubMed Central PMCID: PMC5446210.
- Wang C, Nishijima K, Kitajima S, Niimi M, Yan H, Chen Y, Ning B, Matsuhisa F, Liu E, Zhang J, Chen YE, Fan J. Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits. Arterioscler Thromb Vasc Biol. 2017 May 25. pii: ATVBAHA.117.309139. doi: 10.1161/ATVBAHA.117.309139. [Epub ahead of print] PubMed PMID: 28546217.
- Yang B, Zhou W, Jiao J, Nielsen JB, Mathis MR, Heydarpour M, Lettre G, Folkersen L, Prakash S, Schurmann C, Fritsche L, Farnum GA, Lin M, Othman M, Hornsby W, Driscoll A, Levasseur A, Thomas M, Farhat L, Dubé MP, Isselbacher EM, Franco-Cereceda A, Guo DC, Bottinger EP, Deeb GM, Booher A, Kheterpal S, Chen YE, Kang HM, Kitzman J, Cordell HJ, Keavney BD, Goodship JA, Ganesh SK, Abecasis G, Eagle KA, Boyle AP, Loos RJF, Eriksson P, Tardif JC, Brummett CM, Milewicz DM, Body SC, Willer CJ. Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve. Nat Commun. 2017 May 25;8:15481. doi: 10.1038/ncomms15481. PubMed PMID: 28541271.
- Zhang J, Niimi M, Yang D, Liang J, Xu J, Kimura T, Mathew AV, Guo Y, Fan Y, Zhu T, Song J, Ackermann R, Koike Y, Schwendeman A, Lai L, Pennathur S, Garcia-Barrio M, Fan J, Chen YE. Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1068-1075. doi: 10.1161/ATVBAHA.117.309114. Epub 2017 Apr 20. PubMed PMID: 28428219.
- Chang L, Garcia-Barrio MT, Chen YE. Brown Adipose Tissue, Not Just a Heater. Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):389-391. doi: 10.1161/ATVBAHA.116.308909. PubMed PMID: 28228444.
Lu H, Fan Y, Qiao C, Liang W, Hu W, Zhu T, Zhang J, Chen YE. TFEB inhibits endothelial cell inflammation and reduces atherosclerosis. Sci Signal. 2017 Jan 31;10(464). pii: eaah4214. doi: 10.1126/scisignal.aah4214. PubMed PMID: 28143903. - Wang L, Qiu P, Jiao J, Hirai H, Xiong W, Zhang J, Zhu T, Ma PX, Chen YE, Yang B. Yes-Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage. Stem Cells. 2017 Feb;35(2):351-361. doi: 10.1002/stem.2484. Epub 2016 Sep 20. PubMed PMID: 27571517.
- Jiao J, Xiong W, Wang L, Yang J, Qiu P, Hirai H, Shao L, Milewicz D, Chen YE, Yang B. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves. EBioMedicine. 2016 Aug;10:282-90. doi: 10.1016/j.ebiom.2016.06.045. Epub 2016 Jul 1. PubMed PMID: 27394642; PubMed Central PMCID: PMC5006642.
- Wang Z, Zhang J, Li H, Li J, Niimi M, Ding G, Chen H, Xu J, Zhang H, Xu Z, Dai Y, Gui T, Li S, Liu Z, Wu S, Cao M, Zhou L, Lu X, Wang J, Yang J, Fu Y, Yang D, Song J, Zhu T, Li S, Ning B, Wang Z, Koike T, Shiomi M, Liu E, Chen L, Fan J, Chen YE, Li Y. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models. Scientific Reports. 2016. 1;6:26942. doi: 10.1038/srep26942. PMID: 27245873.
- Yang D, Song J, Zhang JF, Xu J, Zhu T, Wang Z, Lai L, Chen YE. Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression. Scientific Reports. 2016. 6:25161. doi: 10.1038/srep25161. PMID: 27117226.
- Song J, Yang D, Xu J, Zhu T, Chen YE, Zhang JF. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency. Nat Commun. 2016 Jan 28;7:10548. doi: 10.1038/ncomms10548. PMID: 26817820.
- Kuai R, Li D, Chen YE, Moon JJ, Schwendeman A. High-Density Lipoproteins: Nature's Multifunctional Nanoparticles. ACS Nano. 2016 Mar 22;10(3):3015-41.
- Fan Y, Lu H, Guo Y, Zhu T, Garcia-Barrio MT, Jiang Z, Willer CJ, Zhang J, Chen YE. Hepatic Transmembrane 6 Superfamily Member 2 Regulates Cholesterol Metabolism in Mice. Gastroenterology. 2016 May;150(5):1208-18.
- Zhang X, Li Y, Chen YE, Chen J, Ma PX. Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects. Nat Commun. 2016 Jan 14;7:10376. doi: 10.1038/ncomms10376.
- Fan J, Kitajima S, Watanabe T, Xu J, Zhang J, Liu E, Chen YE. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Pharmacol Ther. 2015 Feb; 146:104-19.
- Wang Y, Hu J, Jiao J, Liu Z, Zhou Z, Zhao C, Chang LJ, Chen YE, Ma PX, Yang B. Engineering vascular tissue with functional smooth muscle cells derived from human iPS cells and nanofibrous scaffolds. Biomaterials. 2014 Oct;35 (32):8960-9.
- Yang D, Xu J, Zhu T, Fan J, Lai L, Zhang JF, Chen YE. Effective gene targeting in rabbits using RNA-guided Cas9 nucleases. Journal of Molecular Cell Biology. 2014. 6(1):97-9.
- Li X, Yang Y, Bu L, Guo X, Tang C, Song J, Fan N, Zhao B, Ouyang Z, Liu Z, Zhao Y, Yi X, Quan L, Liu S, Yang Z, Ouyang H, Chen YE, Wang Z, Lai L. Rosa26-targeted swine models for stable gene over-expression and Cre-mediated lineage tracing. Cell Res. 2014 Feb 7. doi: 10.1038/cr.2014.15. [Epub ahead of print]
- Yang D, Zhang JF, Xu J, Zhu TQ, Fan YB, Fan JL, and Chen YE. Production of Apolipoprotein C-III knockout rabbits using Zinc Finger Nucleases. Journal of Visualized Experiments. 2013. (81), e50957, doi:10.3791/50957.