Iain A. Drummond
Department of Medicine,
Department of Genetics
Renal Unit- CNY 8
149 13th Street
Charlestown, MA 02129
Visit my lab page here.
We study kidney organogenesis using the zebrafish to explore conserved molecular mechanisms underlying organ cell specification, differentiation and tissue patterning. We also study organ pathologies that result from mutations in genes required for cilia biogenesis and function. These include kidney cystic disease, retinal degeneration and left-right asymmetry defects.
Kidney cell differentiation and nephron regeneration. Our studies of the odd skipped related1 zinc finger transcription factor have revealed a role for wnt signaling in pronephric epithelial differentiation and angioblast patterning. We are now extending these studies to characterize the role of wnt signaling during regeneration of adult kidneys.
Cilia and organogenesis. Kidney cystic disease, retinal degeneration and left-right asymmetry defects can all be linked to defects in cilia structure and function. We are positionally cloning zebrafish cystic kidney mutants to further understand the roles of cilia in development and disease. We are also analysing transcriptional networks that control ciliogenesis and how patterning of ciliated cells is controlled during development and disease. We find that the double bubble mutant gene encodes IFT172, a gene required for cilia formation. The fleer mutant encodes a novel TPR repeat protein that regulates tubulin polyglutamylation and ciliogenesis. We also find that the transcription factor foxj1 is induced by injury and controls ciliogenesis in response to physiological signals.
Modeling Human disease in zebrafish. Modeling human kidney diseases in the zebrafish creates opportunities to better understand disease mechanisms and screen for treatments. Human polycystic kidney disease (PKD) is one of the most common genetic diseases. Mutation or knockdown of polycystins in zebrafish results in abnormally persistent extracellular matrix synthesis and consequent axis defects. Our current work is focused on how polycystins act as negative feedback regulators of morphogenesis and repress embryonic gene expression once organogenesis is complete.
Mudumana S.P., Hentschel D., Liu Y., Vasilyev A., Drummond I.A. 2008. odd skipped related1 reveals a novel role for endoderm in regulating kidney versus vascular cell fate. Development. 2008 Oct;135(20):3355-67
Liu, Y., Pathak, N., Kramer-Zucker, A. and Drummond, I.A. 2007. Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. Development, 134:1111-22.
Mangos, S., Lam, P.Y., Zhao, A., Liu, Y., Mudumana, S., Vasilyev, A., Liu, A., and Drummond, I.A. 2010. The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation. Dis Model Mech 3, 354-365.
Vasilyev, A., Liu, Y., Mudumana, S.P., Steve Mangos, S., Lam, P., Majumdar, A., Jinhua Zhao, J., Poon, K-L, Kondrychyn, I., Korzh, V., and Iain A. Drummond, I.A. 2009. Collective Cell Migration Drives Morphogenesis of the Kidney Nephron. PLoS Biology Jan 6;7(1):e9
For a complete listing of publications click here.
Last Update: 7/26/2012