Chenleng Cai, PhD
- ASSOCIATE PROFESSOR | Cell, Developmental & Regenerative Biology
Research Topics:Cardiovascular, Developmental Biology, Embryology, Stem Cells
For more information, please visit the Cai Laboratory website.
Multi-Disciplinary Training AreasDevelopmental and Stem Cell Biology [DSCB], Genetics and Genomic Sciences [GGS]
Independent Investigator Award
Basil O'Connor Starter Scholar
National Scientist Development Grant
Summary of Research Studies:
Cardiogenesis, the induction and subsequent development of the heart, is a critical event during embryogenesis. Mutations in genes expressed in the early heart cause defective cardiac development, and are responsible for embryonic lethality and congenital heart disease, occurring in ~1% of live births and 10% of stillbirths in humans. The Cai laboratory uses mouse as a model system to study the molecular pathways controlling heart development and disease. Uncovering signaling cascades underlying early heart development also has great implications for the research of cardiac regenerative biology. Dr. Cai's previous research has showed that Isl1 (Islet1), a Lim-homeodomain transcription factor, labels a cardiac progenitor population that gives rise to the majority of cardiac segments (right ventricle, outflow tract and atria). Loss of Isl1 results in a malformed heart that lacks these cardiac segments during early heart development. In addition to the study of Isl1, Dr. Cai also discovered that T-box transcription factor Tbx20 plays critical roles in regulating cardiac cell proliferation and specification. More recently, Dr. Cai identified another cardiac progenitor population, Tbx18-expressing proepicardial and epicardial cells that can gives rise to both myocytes and non-myocytes cardiac lineages during early heart development. The Cai laboratory is currently performing research to decipher the transcriptional networks of Isl1 and Tbx20 in heart development. They are also interested in exploring the therapeutic potential of Isl1 and Tbx18 progenitor cells in cardiac repair and regeneration.
For more information, please visit the Cai Laboratory website.
Beharry KD, Cai CL, Valencia GB, Lazzaro D, Valencia AM, Salomone F, Aranda JV. Human retinal endothelial cells and astrocytes cultured on 3-D scaffolds for ocular drug discovery and development. Prostaglandins & other lipid mediators 2017 Sep;.
Tan JJ, Cai CL, Shrier EM, McNally L, Lazzaro DR, Aranda JV, Beharry KD. Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy. Journal of ophthalmology 2017 Jul; 2017.
Li J, Miao L, Zhao C, Shaikh Qureshi WM, Shieh D, Guo H, Lu Y, Hu S, Huang A, Zhang L, Cai CL, Wan LQ, Xin H, Vincent P, Singer HA, Zheng Y, Cleaver O, Fan ZC, Wu M. CDC42 is required for epicardial and pro-epicardial development by mediating FGF receptor trafficking to the plasma membrane. Development (Cambridge, England) 2017 May; 144(9).
Racedo SE, Hasten E, Lin M, Devakanmalai GS, Guo T, Ozbudak EM, Cai CL, Zheng D, Morrow BE. Reduced dosage of β-catenin provides significant rescue of cardiac outflow tract anomalies in a Tbx1 conditional null mouse model of 22q11.2 deletion syndrome. PLoS genetics 2017 Mar; 13(3).
Cai CL, Molkentin JD. The Elusive Progenitor Cell in Cardiac Regeneration: Slip Slidin' Away. Circulation research 2017 Jan; 120(2).
Ye W, Song Y, Huang Z, Osterwalder M, Ljubojevic A, Xu J, Bobick B, Abassah-Oppong S, Ruan N, Shamby R, Yu D, Zhang L, Cai CL, Visel A, Zhang Y, Cobb J, Chen Y. A unique stylopod patterning mechanism by Shox2 controlled osteogenesis. Development (Cambridge, England) 2016 Jun;.
Yan J, Zhang L, Sultana N, Oh JG, Wu B, Hajjar RJ, Zhou B, Cai CL. A series of robust genetic indicators for definitive identification of cardiomyocytes. Journal of molecular and cellular cardiology 2016 Jun;.
Sultana N, Zhang L, Yan J, Chen J, Cai W, Razzaque S, Jeong D, Sheng W, Bu L, Xu M, Huang GY, Hajjar RJ, Zhou B, Moon A, Cai CL. Resident c-kit(+) cells in the heart are not cardiac stem cells. Nature communications 2015 Oct; 6.
Yan J, Zhang L, Sultana N, Park DS, Shekhar A, Bu L, Hu J, Razzaque S, Cai CL. A Murine Myh6MerCreMer Knock-In Allele Specifically Mediates Temporal Genetic Deletion in Cardiomyocytes after Tamoxifen Induction. PloS one 2015 Jul; 10(7).
Yan J, Sultana N, Zhang L, Park DS, Shekhar A, Hu J, Bu L, Cai CL. Generation of a tamoxifen inducible Tnnt2(MerCreMer) knock-in mouse model for cardiac studies. Genesis (New York, N.Y. : 2000) 2015 May;.
Shamis Y, Cullen DE, Liu L, Yang G, Ng SF, Xiao L, Bell FT, Ray C, Takikawa S, Moskowitz IP, Cai CL, Yang X, Li X. Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development. Proceedings of the National Academy of Sciences of the United States of America 2015 Apr;.
Wu M, Peng S, Yang J, Tu Z, Cai X, Cai CL, Wang Z, Zhao Y. Baf250a orchestrates an epigenetic pathway to repress the Nkx2.5-directed contractile cardiomyocyte program in the sinoatrial node. Cell research 2014 Aug;.
Yan J, Zhang L, Xu J, Sultana N, Hu J, Cai X, Li J, Xu PX, Cai CL. Smad4 Regulates Ureteral Smooth Muscle Cell Differentiation during Mouse Embryogenesis. PloS one 2014 Aug; 9(8).
Zhang L, Nomura-Kitabayashi A, Sultana N, Cai W, Cai X, Moon AM, Cai CL. Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development. Developmental biology 2014 Jun; 390(1).
Wang J, Li Z, He Y, Pan F, Chen S, Rhodes S, Nguyen L, Yuan J, Jiang L, Yang X, Weeks O, Liu Z, Zhou J, Ni H, Cai CL, Xu M, Yang FC. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice. Blood 2014 Jan; 123(4).
Cai X, Hu J, Zhang L, Sultana N, Wu B, Cai W, Zhou B, Cai CL. Tbx20 acts upstream of Wnt signaling to regulate endocardial cushion formation and valve remodeling during mouse cardiogenesis. Development (Cambridge, England) 2013 Aug; 140(15).
Grisanti L, Clavel C, Cai X, Rezza A, Tsai SY, Sennett R, Mumau M, *Cai CL, *Rendl M. Tbx18 targets dermal condensates for labeling, isolation, and gene ablation during embryonic hair follicle formation. The Journal of investigative dermatology 2013 Feb; 133(2): *co-corresponding authors.
Clavel C, Grisanti L, Zemla R, Rezza A, Barros R, Sennett R, Mazloom AR, Chung CY, Cai X, Cai CL, Pevny L, Nicolis S, Ma'ayan A, Rendl M. Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP signaling in differentiating hair shaft progenitors. Developmental cell 2012 Nov; 23(5).
Shen T, Aneas I, Sakabe N, Dirschinger RJ, Wang G, Smemo S, Westlund JM, Cheng H, Dalton N, Gu Y, Boogerd CJ, Cai CL, Peterson K, Chen J, Nobrega MA, Evans SM. Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function. The Journal of clinical investigation 2011 Dec; 121(12).
Cai X, Nomura-Kitabayashi A, Cai W, Yan J, Christoffels VM, Cai CL. Myocardial Tbx20 regulates early atrioventricular canal formation and endocardial epithelial-mesenchymal transition via Bmp2. Developmental biology 2011 Dec; 360(2).
Zhang W, Chen H, Wang Y, Yong W, Zhu W, Liu Y, Wagner GR, Payne RM, Field LJ, Xin H, Cai CL, Shou W. Tbx20 transcription factor is a downstream mediator for bone morphogenetic protein-10 in regulating cardiac ventricular wall development and function. The Journal of biological chemistry 2011 Oct; 286(42).
Li Z, Cai X, Cai CL, Wang J, Zhang W, Petersen BE, Yang FC, Xu M. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood 2011 Oct; 118(17).
Nie X, Sun J, Gordon RE, Cai CL, Xu PX. SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation. Development (Cambridge, England) 2010 Mar; 137(5).
Du A, Hunter CS, Murray J, Noble D, Cai CL, Evans SM, Stein R, May CL. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes 2009 Sep; 58(9).
Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X, Stallcup WB, Denton CP, McCulloch A, Chen J, Evans SM. A myocardial lineage derives from Tbx18 epicardial cells. Nature 2008 Jul; 454(7200).
Lin L, Cui L, Zhou W, Dufort D, Zhang X, Cai CL, Bu L, Yang L, Martin J, Kemler R, Rosenfeld MG, Chen J, Evans SM. Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proceedings of the National Academy of Sciences of the United States of America 2007 May; 104(22).
Sun Y, Liang X, Najafi N, Cass M, Lin L, Cai CL, Chen J, Evans SM. Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Developmental biology 2007 Apr; 304(1).
Song MR, Shirasaki R, Cai CL, Ruiz EC, Evans SM, Lee SK, Pfaff SL. T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration. Development (Cambridge, England) 2006 Dec; 133(24).
Ai D, Liu W, Ma L, Dong F, Lu MF, Wang D, Verzi MP, Cai C, Gage PJ, Evans S, Black BL, Brown NA, Martin JF. Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium. Developmental biology 2006 Aug; 296(2).
Lin L, Bu L, Cai CL, Zhang X, Evans S. Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Developmental biology 2006 Jul; 295(2).
Park EJ, Ogden LA, Talbot A, Evans S, Cai CL, Black BL, Frank DU, Moon AM. Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling. Development (Cambridge, England) 2006 Jun; 133(12).
Yang L, Cai CL, Lin L, Qyang Y, Chung C, Monteiro RM, Mummery CL, Fishman GI, Cogen A, Evans S. Isl1Cre reveals a common Bmp pathway in heart and limb development. Development (Cambridge, England) 2006 Apr; 133(8).
Cai CL, Zhou W, Yang L, Bu L, Qyang Y, Zhang X, Li X, Rosenfeld MG, Chen J, Evans S. T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis. Development (Cambridge, England) 2005 May; 132(10).
Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 2005 Feb; 433(7026).
Huang C, Sheikh F, Hollander M, Cai CL, Becker D, Chu PH, Evans S, Chen J. Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis. Development (Cambridge, England) 2003 Dec; 130(24).
Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Developmental cell 2003 Dec; 5(6).
Sparrow DB, Cai CL, Kotecha S, Latinkic B, Cooper B, Towers N, Evans SM, Mohun TJ. Regulation of the tinman homologues in Xenopus embryos. Developmental biology 2000 Nov; 227(1).
Shi Y, Katsev S, Cai CL, Evans S. BMP signaling is required for heart formation in vertebrates. Developmental biology 2000 Aug; 224(2).
Chu PH, Ruiz-Lozano P, Zhou Q, Cai CL, Chen J. Expression patterns of FHL/SLIM family members suggest important functional roles in skeletal muscle and cardiovascular system. Mechanisms of development 2000 Jul; 95(1-2).