Norann A. Zaghloul
- BA (1999) Johns Hopkins University
- MS (2001) George Washington University
- PhD (2006) George Washington University
- Post-Doc Fellowship (2010) Johns Hopkins University
Our research focuses on understanding the function of genes that cause complex metabolic phenotypes, such as diabetes and obesity. To investigate this problem, we are pursuing two lines of questioning:
Functional assessment of genes associated with common, complex disorders: Using the zebrafish system and cell models, we are investigating how common variants in disease-associated genes produce metabolic phenotypes. We use targeted disruption of gene expression in zebrafish embryos or cultured cell lines as well as addition of environmental factors, such as high fat diet, to understand what aspects of disease are regulated by susceptibility genes. Our goal is to understand how genetic variants contribute to disease risk and how that contribution is exacerbated in the presence of environmental triggers.
Investigation of rare disorders characterized by obesity and other related features: Disorders that are caused by defects in primary cilia (ciliopathies) display obesity and other metabolic syndrome defects. To understand this, we are investigating how ciliopathy genes contribute to developmental defects in organ systems – such as pancreas and hypothalamus - that might underlie obesity and diabetes. By focusing on such defects in the context of ciliopathies, we hope to understand the pathways that contribute to these phenotypes and shed light onto other more common diseases with similar features.
Lab Techniques and Equipment:
Our lab utilizes zebrafish and cell culture techniques.
A complete list of Dr. Zaghloul's publications can be found in PubMed.
- Gerdes, J.M., Liu, Y., Zaghloul, N.A., Leitch, C.L., Lawson, S.S., Kato, M., Beachy, P.A., Beales, P.L., DeMartino, G.N., Fisher, S., Badano, J.L. and Katsanis, N. (2007) "Disruption of the basal body compromises proteosomal function and perturbs intracellular Wnt response." Nature Genetics, 39:1350-60.
- Leitch, C.C., Zaghloul, N.A., Davis, E.E., Stoetzel, C., Diaz-Font, A., Rix, S., Al-Fadhel, M., Lewis, R.A., Eyaid, W., Banin, E., Dollfus, H., Beales, P.L., Badano, J.L. and Katsanis, N. (2008) "Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome." Nature Genetics, 40: 443-8.
- Zaghloul, N.A. Katsanis, N. (2009) "Mechanistic insights into Bardet-Biedl Syndrome: a model ciliopathy." Journal of Clinical Investigation, 119:428-437.
- Zaghloul, N.A. and Katsanis, N. (2010) "Functional modules, mutational load and human genetic disease." Trends in Genetics, 26(4): 168-176.
- Zaghloul, N.A., Liu, Y., Gerdes, J.M., Gascue, C., Oh, E.C., Leitch, C.C., Bromberg, Y., Binkley, J., Leibel, R.L., Sidow, A., Badano, J.L., Katsanis, N. (2010) "Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet-Biedl Syndrome." Proc Nat Acad Sci USA, 107(23): 10602-7.
- Zaghloul, N.A. and Brugmann, S.A. (2011) "The emerging face of primary cilia." Genesis, 49: 231-46.
- Kim, S., Zaghloul, N.A., Bubenshchikova, E., Oh, E.C., Rankin, S., Katsanis, N., Obara, T., Tsiokas, L. (2011) "Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry." Nature Cell Biology, 13: 351-60.
- Leitch, C.C., Lodh, S., Prieto-Echague, V., Badano, J.L., Zaghloul, N.A. (2014) "Basal body proteins regulate Notch signaling via endosomal trafficking." Journal of Cell Science, Jun 1;127(Pt 11):2407-19.
- Liu YP, Tsai, I., Morleo, M., Oh, E.C., Leitch, C.C., Massa, F., Lee, B., Parker, D.S., Finley, Zaghloul, N.A., Franco, B., Katsanis, N. (2014) Ciliopathy proteins regulate paracrine signaling by proteasomal degradation of mediators. Journal of Clinical Investigation, 2014 May 1;124(5): 2059-70.
- Lodh, S., O’Hare, E.A., Zaghloul, N.A. (2014) "Primary cilia in pancreatic development and disease." Birth Defects Research Part C: Embryo Today: Reviews. 2014 Jun;102(2):139-58.
- Leitch, C.C. Zaghloul, N.A. (2014) "BBS4 is necessary for ciliary localization of TrkB receptor and activation by BDNF." PLoS ONE, 2014 May 27;9(5):e98687.
- O'Hare, E.A., Wang, X., Montasser, M.E., Chang, Y.C., Mitchell, B.D., Zaghloul, N.A. (2014) "Disruption of ldlr causes increased LDL-cholesterol and vascular lipid accumulation in a zebrafish model of hypercholesterolemia." Journal of Lipid Research, 55(11): 2242-53.
- Elkon, R., Milon, B., Morrison, L., Shah, M., Vijayakumar, S., Racherla, M., Leitch, C.C., Silipino, L., Hadi, S., Weiss-Gayet, M., Barras, E., Schmid, C.D., Ait-Lounis, A., Barnes, A., Eisenman, D.J., Frolenkov, G.I., Strome, S.E., Durand, B., Zaghloul, N.A., Jones, S.M., Reith, W., Hertzano, R. (2015) "Transcriptome analysis of inner ear hair cells discovers a novel role for RFX in hearing" Nature Communications, Oct 15; 6:8549
- Lodh, S., Hostelly, T.L., Leitch, C.C., O’Hare, E.A., Zaghloul, N.A. (2015) "Differential effects on ß-cell mass by disruption of Bardet-Biedl Syndrome and Alsrom Syndrome genes." Human Molecular Genetics, 25(1): 57-68. Epub 2015 Oct 22.
- O'Hare, E.A., Yerges-Armstrong, L., Perry, J.A., Shuldiner, A.R., Zaghloul, N.A. (2016) "Assignment of functional relevance to genes at type 2 diabetes-associated loci through investigation of ß-cell mass deficits." Molecular Endocrinology, 30(4): 429-445.
- Khan, S.Y., Kabir, F., Khan, A.O., Lee, W., Chaerkady, R., Ma, Z., Leitch, C.C., Sabir, N., Khan, S.N., Riazuddin, S., Al-Mesfer, S., Al-Turkmani, S., Talbot Jr., C.C., Cole, R.N., Kantorow, M., Pourmand, N., Gottsch, J.D., Zaghloul, N.A., Hejtmancik, J.F., Riazuddin, S.A. (2016) "FOXE3 Contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1" Nature Communications, Apr 6; 7:10953.
- Hostelley, T.L., Lodh, S., Zaghloul, N.A. (2016) "Whole organism transcriptome analysis of zebrafish models of Bardet-Biedl Syndrome and Alstom Syndrome provides mechanistic insight into shared and divergenet phenotypes." BMC Genomics, 2016, 17:318.