Iain A. Drummond, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5647
Fax: (617) 726-5669


idrummon@receptor.mgh.harvard.edu

Iain A. Drummond, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Associate Biologist, Renal Unit, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research focuses on kidney development and the regulation of renal cell

differentiation. The zebrafish, as a model system for vertebrate

organogenesis, offers many experimental advantages for studies of kidney

development. Large scale mutant screens taking advantage of the optical

transparency of zebrafish embryos have isolated many mutants with kidney

defects. Our analysis of the mutant no isthmus, which carries mutations in

the zebrafish pax2.1 gene, has revealed an essential role for pax2.1 in

pronephric tubule development and for restricting Wilms tumor suppressor

(wt1) gene expression to developing podocytes. Further studies are aimed at studying genes that function earlier than pax2.1 and may regulate its expression. A large group of mutants show defects in

the development of epithelial polarity and subsequent development of cysts

in the pronephros. We have positionally cloned two of these genes and found that they function in epithelial cilia and in membrane protein trafficking. We are also studying homologs of human autosomal dominant polycystic kidney disease genes and their role in normal kidney function. Finally we have used the zebrafish to define the function of a novel podocyte gene that is essential for cell junction formation.

Publications

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  • Slaats GG, Ghosh AK, Falke LL, Le Corre S, Shaltiel IA, van de Hoek G, Klasson TD, Stokman MF, Logister I, Verhaar MC, Goldschmeding R, Nguyen TQ, Drummond IA, Hildebrandt F, Giles RH. Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition. PLoS Genet. 2014; 10:e1004594. PubMed
  • Yeo NC, O'Meara CC, Bonomo JA, Veth KN, Tomar R, Flister MJ, Drummond IA, Bowden DW, Freedman BI, Lazar J, Link BA, Jacob HJ. Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity. Genome Res 2014. PubMed
  • Terashima AV, Mudumana SP, Drummond IA. Odd skipped related 1 is a negative feedback regulator of nodal-induced endoderm development. Dev Dyn 2014. PubMed
  • Jin D, Ni TT, Sun J, Wan H, Amack JD, Yu G, Fleming J, Chiang C, Li W, Papierniak A, Cheepala S, Conseil G, Cole SP, Zhou B, Drummond IA, Schuetz JD, Malicki J, Zhong TP. Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport. Nat Cell Biol 2014; 16:841-51. PubMed
  • Pathak N, Austin-Tse CA, Liu Y, Vasilyev A, Drummond IA. Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function. Mol Biol Cell 2014. PubMed
  • Tomar R, Mudumana SP, Pathak N, Hukreide NA, Drummond IA. osr1 Is Required for Podocyte Development Downstream of wt1a. J Am Soc Nephrol 2014. PubMed
  • Le Corre S, Eyre D, Drummond IA. Modulation of the Secretory Pathway Rescues Zebrafish Polycystic Kidney Disease Pathology. J Am Soc Nephrol 2014. PubMed
  • Thomas S, Wright KJ, Le Corre S, Micalizzi A, Romani M, Abhyankar A, Saada J, Perrault I, Amiel J, Litzler J, Filhol E, Elkhartoufi N, Kwong M, Casanova JL, Boddaert N, Baehr W, Lyonnet S, Munnich A, Burglen L, Chassaing N, Encha-Ravazi F, Vekemans M, Gleeson JG, Valente EM, Jackson PK, Drummond IA, Saunier S, Attié-Bitach T. A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium. Hum Mutat 2014; 35:137-46. PubMed
  • Palmyre A, Lee J, Ryklin G, Camarata T, Selig MK, Duchemin AL, Nowak P, Arnaout MA, Drummond IA, Vasilyev A. Collective epithelial migration drives kidney repair after acute injury. PLoS ONE 2014; 9:e101304. PubMed
  • Burger A, Vasilyev A, Tomar R, Selig MK, Nielsen GP, Peterson RT, Drummond IA, Haber DA. A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12. Dis Model Mech 2013. PubMed
  • Lam PY, Kamei CN, Mangos S, Mudumana S, Liu Y, Drummond IA. odd-skipped related 2 is required for fin chondrogenesis in zebrafish. Dev Dyn 2013; 242:1284-92. PubMed
  • Austin-Tse C, Halbritter J, Zariwala MA, Gilberti RM, Gee HY, Hellman N, Pathak N, Liu Y, Panizzi JR, Patel-King RS, Tritschler D, Bower R, O'Toole E, Porath JD, Hurd TW, Chaki M, Diaz KA, Kohl S, Lovric S, Hwang DY, Braun DA, Schueler M, Airik R, Otto EA, Leigh MW, Noone PG, Carson JL, Davis SD, Pittman JE, Ferkol TW, Atkinson JJ, Olivier KN, Sagel SD, Dell SD, Rosenfeld M, Milla CE, Loges NT, Omran H, Porter ME, King SM, Knowles MR, Drummond IA, Hildebrandt F. Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia. Am J Hum Genet 2013; 93:672-86. PubMed
  • Drummond IA. The cilium in lights: new views of an ancient organelle. BMC Biol 2013; 11:74. PubMed
  • Leshchiner I, Alexa K, Kelsey P, Adzhubei I, Austin-Tse CA, Cooney JD, Anderson H, King MJ, Stottmann RW, Garnaas MK, Ha S, Drummond IA, Paw BH, North TE, Beier DR, Goessling W, Sunyaev SR. Mutation mapping and identification by whole-genome sequencing. Genome Res 2012; 22:1541-8. PubMed
  • Panizzi JR, Becker-Heck A, Castleman VH, Al-Mutairi DA, Liu Y, Loges NT, Pathak N, Austin-Tse C, Sheridan E, Schmidts M, Olbrich H, Werner C, Häffner K, Hellman N, Chodhari R, Gupta A, Kramer-Zucker A, Olale F, Burdine RD, Schier AF, O'Callaghan C, Chung EM, Reinhardt R, Mitchison HM, King SM, Omran H, Drummond IA. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms. Nat Genet 2012; 44:714-9. PubMed
  • Vasilyev A, Liu Y, Hellman N, Pathak N, Drummond IA. Mechanical stretch and PI3K signaling link cell migration and proliferation to coordinate epithelial tubule morphogenesis in the zebrafish pronephros. PLoS ONE 2012; 7:e39992. PubMed
  • Pathak N, Austin CA, Drummond IA. Tubulin Tyrosine Ligase-like Genes ttll3 and ttll6 Maintain Zebrafish Cilia Structure and Motility. J Biol Chem 2011; 286:11685-95. PubMed
  • Drummond IA. Polycystins, focal adhesions and extracellular matrix interactions. Biochim Biophys Acta 2011. PubMed
  • Chen LM, Zhao J, Musa-Aziz R, Pelletier MF, Drummond IA, Boron WF. Cloning and characterization of a zebrafish homologue of human AQP1: A bifunctional water and gas channel. Am J Physiol Regul Integr Comp Physiol 2010; 299:R1163-74. PubMed
  • Hellman NE, Liu Y, Merkel E, Austin C, Le Corre S, Beier DR, Sun Z, Sharma N, Yoder BK, Drummond IA. The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch. Proc Natl Acad Sci U S A 2010; 107:18499-504. PubMed
  • Sussman CR, Zhao J, Plata C, Lu J, Daly C, Angle N, DiPiero J, Drummond IA, Liang JO, Boron WF, Romero MF, Chang MH. Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafish. Am J Physiol Cell Physiol 2009; 297:C865-75. PubMed
  • Vasilyev A,Liu Y,Mudumana S,Mangos S,Lam PY,Majumdar A,Zhao J,Poon KL,Kondrychyn I,Korzh V,Drummond IA. Collective cell migration drives morphogenesis of the kidney nephron. PLoS Biol 2009; 7:e9. PubMed
  • Pathak NH, Drummond IA. Polyglutamylation and the fleer gene. Methods Cell Biol. 2010; 94:317-32. PubMed
  • Mudumana SP,Hentschel D,Liu Y,Vasilyev A,Drummond IA. odd skipped related1 reveals a novel role for endoderm in regulating kidney versus vascular cell fate. Development 2008; 135:3355-67. PubMed
  • Moller CC, Mangos S, Drummond IA, Reiser J. Expression of trpC1 and trpC6 orthologs in zebrafish. Gene Expr Patterns 2008; 8:291-296. PubMed
  • Insinna C, Pathak N, Perkins B, Drummond I, Besharse JC. The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development. Dev Biol 2008; 316:160-70. PubMed
  • Pathak N, Obara T, Mangos S, Liu Y, Drummond IA. The zebrafish fleer gene encodes an essential regulator of cilia tubulin polyglutamylation. Mol Biol Cell 2007; 18:4353-64. PubMed
  • Panizzi JR, Jessen JR, Drummond IA, Solnica-Krezel L. New functions for a vertebrate Rho guanine nucleotide exchange factor in ciliated epithelia. Development 2007; 134:921-31. PubMed
  • Liu Y, Pathak N, Kramer-Zucker A, Drummond IA. Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. Development 2007; 134:1111-22. PubMed
  • Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, Hoskins BE, Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkaloglu A, Cleper R, Basel-Vanagaite L, Pohl M, Griebel M, Tsygin AN, Soylu A, Muller D, Sorli CS, Bunney TD, Katan M, Liu J, Attanasio M, O'toole JF, Hasselbacher K, Mucha B, Otto EA, Airik R, Kispert A, Kelley GG, Smrcka AV, Gudermann T, Holzman LB, Nurnberg P, Hildebrandt F. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet 2006; 38:1397-405. PubMed
  • Obara T, Mangos S, Liu Y, Zhao J, Wiessner S, Kramer-Zucker AG, Olale F, Schier AF, Drummond IA. Polycystin-2 immunolocalization and function in zebrafish. J Am Soc Nephrol 2006; 17:2706-18. PubMed
  • Sayer JA, Otto EA, O'Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, Nigg EA, Shou C, Lillo C, Williams DS, Hoppe B, Kemper MJ, Neuhaus T, Parisi MA, Glass IA, Petry M, Kispert A, Gloy J, Ganner A, Walz G, Zhu X, Goldman D, Nurnberg P, Swaroop A, Leroux MR, Hildebrandt F. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet 2006; 38:674-81. PubMed
  • Kramer-Zucker AG, Wiessner S, Jensen AM, Drummond IA. Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes. Dev Biol 2005; 285:316-29. PubMed
  • Kramer-Zucker AG, Olale F, Haycraft CJ, Yoder BK, Schier AF, Drummond IA. Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis. Development 2005; 132:1907-21. PubMed
  • Drummond IA. Zebrafish kidney development. Methods Cell Biol 2004; 76:501-30. PubMed
  • Mangos S, Lam PY, Zhao A, Liu Y, Mudumana S, Vasilyev A, Liu A, Drummond IA. The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation. Dis Model Mech 2010; 3:354-65. PubMed
  • Vasilyev A, Drummond IA. Fluid flow and guidance of collective cell migration. Cell Adh Migr 2010; 4:353-7. PubMed
  • Kim E, Arnould T, Sellin LK, Benzing T, Fan MJ, Gr. The polycystic kidney disease 1 gene product modulates Wnt signaling. J Biol Chem 1999; 274:4947-53. PubMed
  • Majumdar A, Drummond IA. Podocyte differentiation in the absence of endothelial cells as revealed in the zebrafish avascular mutant, cloche. Dev Genet 1999; 24:220-9. PubMed
  • Drummond IA, Majumdar A, Hentschel H, Elger M, Solnica-Krezel L, Schier AF, Neuhauss SC, Stemple DL, Zwartkruis F, Rangini Z, Driever W, Fishman MC. Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function. Development 1998; 125:4655-67. PubMed
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