Nadia Ameen, MBBS
Professor of Pediatrics (Gastroenterology)
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Research Summary
My laboratory has been supported continuously by NIH awards (K08, R03, R01) since 2000. We study intracellular trafficking routes and mechanisms and that regulate the expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in the intestine. CFTR represents the primary exit pathway responsible for anion and fluid secretion on the apical membranes of intestinal cells. Mutations in the CFTR gene result in absence of functional CFTR channels and the genetic disease Cystic Fibrosis while up-regulation of CFTR function is implicated in diarrheal diseases. We employ transgenic animal and polarized intestinal cell models in conjunction with cell biologic, molecular and physiologic approaches to understand the intracellular trafficking routes traversed by CFTR and how alterations in these pathways lead to intestinal diseases.
Extensive Research Description
Our early studies focussed on identification of trafficking as a major mechanism regulating CFTR in the intestine and its relevance to secretory diarrhea. More recently, we investigate a rare genetic diarrheal disease that affect new borns, Microvillus Inclusion Disease(MVID). We were first to show that MVID results from an apical trafficking defect. Current investigations are elucidating kinase signaling mechanisms regulating ion transport that result in diarrhea in MVID.
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Research Interests
Antidiarrheals; Intestinal Diseases
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Selected Publications
- Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine.Ahsan MK, Tchernychev B, Kessler MM, Solinga RM, Arthur D, Linde CI, Silos-Santiago I, Hannig G, Ameen NA. Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine. Physiological Reports 2017, 5.
- AP2 α modulates cystic fibrosis transmembrane conductance regulator function in the human intestine.Kumari V, Desai S, Ameen NA. AP2 α modulates cystic fibrosis transmembrane conductance regulator function in the human intestine. Journal Of Cystic Fibrosis : Official Journal Of The European Cystic Fibrosis Society 2017, 16:327-334.
- Identification of intestinal ion transport defects in microvillus inclusion disease.Kravtsov DV, Ahsan MK, Kumari V, van Ijzendoorn SC, Reyes-Mugica M, Kumar A, Gujral T, Dudeja PK, Ameen NA. Identification of intestinal ion transport defects in microvillus inclusion disease. American Journal Of Physiology. Gastrointestinal And Liver Physiology 2016, 311:G142-55.
- Restoration of cytoskeletal and membrane tethering defects but not defects in membrane trafficking in the intestinal brush border of mice lacking both myosin Ia and myosin VI.Hegan PS, Kravtsov DV, Caputo C, Egan ME, Ameen NA, Mooseker MS. Restoration of cytoskeletal and membrane tethering defects but not defects in membrane trafficking in the intestinal brush border of mice lacking both myosin Ia and myosin VI. Cytoskeleton (Hoboken, N.J.) 2015, 72:455-76.
- Characterization of CFTR High Expresser cells in the intestine.Jakab RL, Collaco AM, Ameen NA. Characterization of CFTR High Expresser cells in the intestine. American Journal Of Physiology. Gastrointestinal And Liver Physiology 2013, 305:G453-65.
- Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport.Collaco AM, Jakab RL, Hoekstra NE, Mitchell KA, Brooks A, Ameen NA. Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport. American Journal Of Physiology. Gastrointestinal And Liver Physiology 2013, 305:G258-75.
- Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR.Collaco AM, Geibel P, Lee BS, Geibel JP, Ameen NA. Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR. American Journal Of Physiology. Cell Physiology 2013, 305:C981-96.
- A unique subset of rat and human intestinal villus cells express the cystic fibrosis transmembrane conductance regulator.Ameen NA, Ardito T, Kashgarian M, Marino CR. A unique subset of rat and human intestinal villus cells express the cystic fibrosis transmembrane conductance regulator. Gastroenterology 1995, 108:1016-23.
- A delta F508 mutation in mouse cystic fibrosis transmembrane conductance regulator results in a temperature-sensitive processing defect in vivo.French PJ, van Doorninck JH, Peters RH, Verbeek E, Ameen NA, Marino CR, de Jonge HR, Bijman J, Scholte BJ. A delta F508 mutation in mouse cystic fibrosis transmembrane conductance regulator results in a temperature-sensitive processing defect in vivo. The Journal Of Clinical Investigation 1996, 98:1304-12.
- CFTR channel insertion to the apical surface in rat duodenal villus epithelial cells is upregulated by VIP in vivo.Ameen NA, Martensson B, Bourguinon L, Marino C, Isenberg J, McLaughlin GE. CFTR channel insertion to the apical surface in rat duodenal villus epithelial cells is upregulated by VIP in vivo. Journal Of Cell Science 1999, 112 ( Pt 6):887-94.
- Cellular localization of the cystic fibrosis transmembrane conductance regulator in mouse intestinal tract.Ameen N, Alexis J, Salas P. Cellular localization of the cystic fibrosis transmembrane conductance regulator in mouse intestinal tract. Histochemistry And Cell Biology 2000, 114:69-75.
- Subcellular distribution of CFTR in rat intestine supports a physiologic role for CFTR regulation by vesicle traffic.Ameen NA, van Donselaar E, Posthuma G, de Jonge H, McLaughlin G, Geuze HJ, Marino C, Peters PJ. Subcellular distribution of CFTR in rat intestine supports a physiologic role for CFTR regulation by vesicle traffic. Histochemistry And Cell Biology 2000, 114:219-28.
- Anomalous apical plasma membrane phenotype in CK8-deficient mice indicates a novel role for intermediate filaments in the polarization of simple epithelia.Ameen NA, Figueroa Y, Salas PJ. Anomalous apical plasma membrane phenotype in CK8-deficient mice indicates a novel role for intermediate filaments in the polarization of simple epithelia. Journal Of Cell Science 2001, 114:563-75.
- Microvillus inclusion disease: a genetic defect affecting apical membrane protein traffic in intestinal epithelium.Ameen NA, Salas PJ. Microvillus inclusion disease: a genetic defect affecting apical membrane protein traffic in intestinal epithelium. Traffic (Copenhagen, Denmark) 2000, 1:76-83.
- Fulminant hepatic failure: Wilson's disease or autoimmune hepatitis? Implications for transplantation.Santos RG, Alissa F, Reyes J, Teot L, Ameen N. Fulminant hepatic failure: Wilson's disease or autoimmune hepatitis? Implications for transplantation. Pediatric Transplantation 2005, 9:112-6.
- Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner.Saha T, Aoun J, Hayashi M, Ali SI, Sarkar P, Bag PK, Leblanc N, Ameen N, Woodward OM, Hoque KM. Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner. Biochemistry And Biophysics Reports 2021, 25:100912.