Cecilia Lo, Ph.D.

  • Distinguished Professor and F. Sargent Cheever Chair
  • Department of Developmental Biology

Education & Training

  • Ph.D. in Cell and Developmental Biology from Rockefeller University, New York, NY, 1979
  • B.S. in Biology from Massachusetts Institute of Technology, Cambridge, MA, 1974

Research Interest Summary

developmental etiology and the complex genetics of human congenital heart disease

Research Categories

Research Interests

Research interests in my lab are focused on investigating the developmental and genetic etiology of congenital heart disease.  These studies use systems approach with large scale forward genetic analysis in mice combined with next generation sequencing in mice and patients to elucidate the genetic etiology of congenital heart disease.  Using noninvasive fetal echocardiography, we have conducted a large scale screen of nearly 100,000 fetal mice and identified over 100 genes causing congenital heart disease.   Our findings in the mouse models have helped to inform the genes and developmental pathways that can contribute to human congenital heart disease.  Our studies have led to the discovery of an important role for the cilium and the endocytic/vesicular trafficking in cardiovascular development and congenital heart disease. 

 Findings from our mouse and human studies have suggested a more complex oligogenic etiology for congenital heart disease.  This more complex genetic model is being experimentally tested in mouse and zebrafishbased on mutations identified in patients with congenital heart disease.  In parallel to the animal modeling experiments, we are conducting human clinical studies, interrogating the genetic etiology of human congenital heart disease, and also investigating the potential contribution of cilia related mutations in increasing postsurgical morbidity/mortality and worse neurodevelopmental outcomes.   The overarching goal of research in my laboratory is to combine animal modeling studies  with human clinical research to develop clinical translational approaches for improving the prognosis and long term outcome for children with congenital heart disease.

Representative Publications

Nakhleh N, Francis R, Giese RA, Tian X, Li Y, Zariwala MA, Yagi H, Khalifa O, Kureshi S, Chatterjee B, Sabol SL, Swisher M, Connelly PS, Daniels MP, Srinivasan A, Kuehl K, Kravitz N, Burns K, Sami I, Omran H, Barmada M, Olivier K, Chawla KK, Leigh M, Jonas R, Knowles M, Leatherbury L, Lo CW. High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy. Circulation. 2012 May 8;125(18):2232-42. PubMed PMID: 22499950; PubMed Central PMCID: PMC3770728.

Kim AJ, Francis R, Liu X, Devine WA, Ramirez R, Anderton SJ, Wong LY, Faruque F, Gabriel GC, Chung W, Leatherbury L, Tobita K, Lo CW. Microcomputed tomography provides high accuracy congenital heart disease diagnosis in neonatal and fetal mice. Circ Cardiovasc Imaging. 2013 Jul;6(4):551-9. PubMed PMID: 23759365; PubMed Central PMCID: PMC3908688.

Cui C, Chatterjee B, Lozito TP, Zhang Z, Francis RJ, Yagi H, Swanhart LM, Sanker S, Francis D, Yu Q, San Agustin JT, Puligilla C, Chatterjee T, Tansey T, Liu X, Kelley MW, Spiliotis ET, Kwiatkowski AV, Tuan R, Pazour GJ, Hukriede NA, Lo CW. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton. PLoS Biol. 2013 Nov;11(11):e1001720. PubMed PMID: 24302887; PubMed Central PMCID: PMC3841097.

Liu X, Francis R, Kim AJ, Ramirez R, Chen G, Subramanian R, Anderton S, Kim Y, Wong L, Morgan J, Pratt HC, Reinholdt L, Devine W, Leatherbury L, Tobita K, Lo CW. Interrogating congenital heart defects with noninvasive fetal echocardiography in a mouse forward genetic screen. Circ Cardiovasc Imaging. 2014 Jan;7(1):31-42. PubMed PMID: 24319090; PubMed Central PMCID: PMC3962690.

Li Y, Klena NT, Gabriel GC, Liu X, Kim AJ, Lemke K, Chen Y, Chatterjee B, Devine W, Damerla RR, Chang C, Yagi H, San Agustin JT, Thahir M, Anderton S, Lawhead C, Vescovi A, Pratt H, Morgan J, Haynes L, Smith CL, Eppig JT, Reinholdt L, Francis R, Leatherbury L, Ganapathiraju MK, Tobita K, Pazour GJ, Lo CW. Global genetic analysis in mice unveils central role for cilia in congenital heart disease. Nature. 521: 520-524.(2015). PMID: 25807483.

Quinn, S., Zahid, M., Durkin, J., Francis, R., Lo, C.W., Chennubhotla, C. Automated identification of abnormal respiratory ciliary motion in nasal biopsies. Science Translational Medicine 2015. 7(299):299ra1247

Li, Y., Yagi, H., Onuoha, O., Damerla, R.R., Francis, R., Furutani, Y., Tariq, M., King, S.M., Hendricks, G., Cui, C., Lee, D.M., Zahid, M., Sami, I., Leatherbury, L., Pazour, G.J., Ware, S.M., Nakanishi, T., Goldmuntz, E., Tsang, M., C.W. Lo.  DNAH6 and its interactions with PCD genes in heterotaxy and primary ciliary dyskinesia. PLOS Genet. 2016. DOI:10.1371/journal.pgen.1005821

Panigrahy, A., Lee, V., Ceschin, R., Zuccoli, G., Beluk, N., Khalifa, O., Votava-Smith, J.K. DeBrunner, M., Munoz, R., Dominina, Y., Morell, V., Wearden, P., De Toldeo Joan Sanchez, Devine, W., Zahid, M., and Lo, C.W.   Brain dysplasia associated with ciliary dysfunction in infants with brain dysplasia.  J Pediatrics 178,141-148 (2016).  PMID:27574995

Manolio,  T.A., Fowler, D.M., Starita, L.M., Haendel, M.A., MacArthur, D.G., Biesecker, L.G., Worthey, E., Chisholm, R.L., Green, E.D., Jacob, H.J., McLeod, H.L., Roden,D. Rodriguez, L.L., William, M.S., Cooper, G.M., Cox, N.J., Herman, G.E., Kingsmore, S., Lo, C.W., Lutz, C., MacRae, C.A., Nussbaum, R.L., Ordovas, J.M., Ramos, E.M., Robinson, P.N., Rubinstein, W.S., Seidman, C., Stranger, B.E., Wang, H., Westerfield, M, Bult, C.  Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research. Cell 169:6-12 (2017).  

Liu, X., Yagi, H. Saeed, S., Bais, A.S., Gabriel, C., Chen, Z., Peterson, K.A., Li,Y., Schwartz, M.C., Reynolds, W.T., Saydmohammed, M., Gibbs, B., Wu, Y., Devine, W., Chatterjee, B., Klena, N.T., Kostka, D., Nikolai T. de Mesy Bentley, K.L., Ganapathiraju, M.K., Dexheimer, P., Leatherbury, L., Khalifa, O., Bhagat, A., Zahid, M., Pu, W., Watkins, S., Grossfeld, P., Muray, S., Porter Jr, G.A., Tsang, M., Martin, L.J., Benson, D.W., Aronow, B.J., Lo, C.W. The complex genetics of hypoplastic left heart syndrome.  Nature Genetics.  49:1152-1159 (2017).

Full List of Publications