Nadia Ameen, MBBS
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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
- CFTR High Expresser Cells in cystic fibrosis and intestinal diseasesdos Reis D, Dastoor P, Santos A, Sumigray K, Ameen N. CFTR High Expresser Cells in cystic fibrosis and intestinal diseases. Heliyon 2023, 9: e14568. PMID: 36967909, PMCID: PMC10031467, DOI: 10.1016/j.heliyon.2023.e14568.
- Loss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID)Ahsan K, dos Reis DC, Barbieri A, Sumigray KD, Nottoli T, Salas PJ, Ameen NA. Loss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID). Journal Of Clinical Medicine 2022, 11: 4179. PMID: 35887942, PMCID: PMC9319011, DOI: 10.3390/jcm11144179.
- Elevated 5‐hydroxytryptamine in COVID‐19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial CellsHoque K, Hayashi M, Sheikh I, Banerjee A, Verma S, Leblanc N, Zeiss C, Ameen N, Chakraborty S. Elevated 5‐hydroxytryptamine in COVID‐19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells. The FASEB Journal 2022, 36: 10.1096/fasebj.2022.36.s1.0r556. PMCID: PMC9348250, DOI: 10.1096/fasebj.2022.36.s1.0r556.
- Serum and Glucocorticoid‐Inducible Kinase 1 (SGK1): An Important Contributor to Diarrhea and Malabsorption in Microvillus Inclusion Disease (MVID)Ahsan K, Reis D, Barbieri A, Sumigray K, Nottoli T, Salas P, Ameen N. Serum and Glucocorticoid‐Inducible Kinase 1 (SGK1): An Important Contributor to Diarrhea and Malabsorption in Microvillus Inclusion Disease (MVID). The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r5730.
- Serum and Glucocorticoid-Inducible Kinase 1 (SGK1): An Important Contributor to Diarrhea and Malabsorption in Microvillus Inclusion Disease (MVID).Ahsan MK, Dos Reis DC, Barbieri A, Sumigray K, Nottoli T, Salas PJ, Ameen NA. Serum and Glucocorticoid-Inducible Kinase 1 (SGK1): An Important Contributor to Diarrhea and Malabsorption in Microvillus Inclusion Disease (MVID). FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2022, 36 Suppl 1 PMID: 35553440, DOI: 10.1096/fasebj.2022.36.S1.R5730.
- Elevated 5-hydroxytryptamine in COVID-19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells.Hoque KM, Hayashi M, Sheikh IA, Banerjee A, Verma SC, Leblanc N, Zeiss CJ, Ameen N, Chakraborty S. Elevated 5-hydroxytryptamine in COVID-19 Stimulates ANO1 Mediated Cl Secretion in Lung & Intestinal Epithelial Cells. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2022, 36 Suppl 1 PMID: 35553771, DOI: 10.1096/fasebj.2022.36.S1.0R556.
- Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent mannerSaha T, Aoun J, Hayashi M, Ali I, 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. PMID: 33537462, PMCID: PMC7838733, DOI: 10.1016/j.bbrep.2021.100912.
- Secretory DiarrheaAmeen N, Kopic S, Ahsan K, Figueroa-Hall L. Secretory Diarrhea. 2020, 41-76. DOI: 10.1007/978-3-030-55310-4_2.
- Intestinal TMEM16A function as a luminal chloride channelKazi M, Saha T, Aoun J, Hayashi M, Sheikh I, Leblanc N, Sarkar P, Ameen N, Woodward O. Intestinal TMEM16A function as a luminal chloride channel. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.06115.
- 36 – Glucocorticoids and Sgk1- Potent Regulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in the IntestineFigueroa-Hall L, Ahsan K, Ahmed M, Kazi M, Ameen N. 36 – Glucocorticoids and Sgk1- Potent Regulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in the Intestine. Gastroenterology 2019, 156: s-14. DOI: 10.1016/s0016-5085(19)36808-8.
- 907 - Deficits in Apical Sodium and Water Transporters Along with Maintenance of CFTR Account for Diarrheal Pathology in MYO5B Ko Mice and Patients with MVIDEngevik A, Engevik M, Meyer A, Shub M, Koepsell H, Ameen N, Tyska M, Goldenring J. 907 - Deficits in Apical Sodium and Water Transporters Along with Maintenance of CFTR Account for Diarrheal Pathology in MYO5B Ko Mice and Patients with MVID. Gastroenterology 2018, 154: s-179. DOI: 10.1016/s0016-5085(18)31009-6.
- Establishment of Microvillus Inclusion Disease (MVID) human models using small intestinal enteroids and embryonic stem cellsFigueroa‐Hall L, Ameen N. Establishment of Microvillus Inclusion Disease (MVID) human models using small intestinal enteroids and embryonic stem cells. The FASEB Journal 2018, 32: 750.31-750.31. DOI: 10.1096/fasebj.2018.32.1_supplement.750.31.
- Linaclotide activates guanylate cyclase‐C/cGMP/protein kinase‐II‐dependent trafficking of CFTR in the intestineAhsan K, 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: e13299. PMID: 28592587, PMCID: PMC5471438, DOI: 10.14814/phy2.13299.
- AP2 α modulates cystic fibrosis transmembrane conductance regulator function in the human intestineKumari V, Desai S, Ameen NA. AP2 α modulates cystic fibrosis transmembrane conductance regulator function in the human intestine. Journal Of Cystic Fibrosis 2017, 16: 327-334. PMID: 28438500, PMCID: PMC5502754, DOI: 10.1016/j.jcf.2017.03.012.
- 986 Deficits in Enterocyte Apical Transporters Associated with Loss of Myosin VBEngevik A, Weis V, Knowles B, Schlegel C, Ameen N, Koepsell H, Zachos N, Donowitz M, Goldenring J. 986 Deficits in Enterocyte Apical Transporters Associated with Loss of Myosin VB. Gastroenterology 2017, 152: s187. DOI: 10.1016/s0016-5085(17)30935-6.
- Identification of intestinal ion transport defects in microvillus inclusion diseaseKravtsov 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. AJP Gastrointestinal And Liver Physiology 2016, 311: g142-g155. PMID: 27229121, PMCID: PMC4967175, DOI: 10.1152/ajpgi.00041.2016.
- Secretory DiarrheaAmeen N, Kopic S, Ahsan M, Kravtsov D. Secretory Diarrhea. 2015, 957-990. DOI: 10.1007/978-1-4939-3366-2_29.
- 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 VIHegan 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 2015, 72: 455-476. PMID: 26286357, PMCID: PMC4715533, DOI: 10.1002/cm.21238.
- Mechanism of Linaclotide‐induced Trafficking of CFTR and NHE3 in the Human Intestinal Cell‐lines Caco‐2 BBe and T84 cellsAhsan K, Silos‐Santiago I, Ameen N. Mechanism of Linaclotide‐induced Trafficking of CFTR and NHE3 in the Human Intestinal Cell‐lines Caco‐2 BBe and T84 cells. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.974.5.
- Mo1752 Linaclotide Induces Endocytosis of the Sodium/Hydrogen Exchanger 3 (NHE3) and Inhibits Sodium AbsorptionAmeen N, Jakab R, Hannig G, Tchernychev B, Arthur D, Silos-Santiago I. Mo1752 Linaclotide Induces Endocytosis of the Sodium/Hydrogen Exchanger 3 (NHE3) and Inhibits Sodium Absorption. Gastroenterology 2014, 146: s-652. DOI: 10.1016/s0016-5085(14)62369-6.
- Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTRCollaco 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-c996. PMID: 23986201, PMCID: PMC4109618, DOI: 10.1152/ajpcell.00067.2013.
- Characterization of CFTR High Expresser cells in the intestineJakab RL, Collaco AM, Ameen NA. Characterization of CFTR High Expresser cells in the intestine. AJP Gastrointestinal And Liver Physiology 2013, 305: g453-g465. PMID: 23868408, PMCID: PMC3761243, DOI: 10.1152/ajpgi.00094.2013.
- Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transportCollaco 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. AJP Gastrointestinal And Liver Physiology 2013, 305: g258-g275. PMID: 23744739, PMCID: PMC3742856, DOI: 10.1152/ajpgi.00485.2012.
- Role of Myosin1a in regulated exocytosis of CFTR in villus enterocytesHoekstra N, Kravtsov D, Mooseker M, Ameen N. Role of Myosin1a in regulated exocytosis of CFTR in villus enterocytes. The FASEB Journal 2013, 27: 913.11-913.11. DOI: 10.1096/fasebj.27.1_supplement.913.11.
- CFTR and V‐ATPase trafficking and function in the intestinal brush border membraneCollaco A, Geibel P, Kravtsov D, Ghantaphang S, Lee B, Geibel J, Ameen N. CFTR and V‐ATPase trafficking and function in the intestinal brush border membrane. The FASEB Journal 2013, 27: 913.10-913.10. DOI: 10.1096/fasebj.27.1_supplement.913.10.
- Characterization of CFTR High Expresser (CHE) cells of the small intestineJakab R, Ameen N. Characterization of CFTR High Expresser (CHE) cells of the small intestine. The FASEB Journal 2013, 27: 913.12-913.12. DOI: 10.1096/fasebj.27.1_supplement.913.12.
- Mo1821 Normalization of CFTR Brush Border Membrane Trafficking Defects in the Intestines of Myosin 1A/6 Double Mutant MiceHoekstra N, Mooseker M, Ameen N. Mo1821 Normalization of CFTR Brush Border Membrane Trafficking Defects in the Intestines of Myosin 1A/6 Double Mutant Mice. Gastroenterology 2012, 142: s-692-s-693. DOI: 10.1016/s0016-5085(12)62674-2.
- Mo1819 Characteristics of Anion Transporter Distribution in Brunner's Glands in Health and DiseaseCollaco A, Mitchell K, Brooks A, Ameen N. Mo1819 Characteristics of Anion Transporter Distribution in Brunner's Glands in Health and Disease. Gastroenterology 2012, 142: s-692. DOI: 10.1016/s0016-5085(12)62672-9.
- Normalization Of CFTR Brush Border Membrane Trafficking Defects In The Intestines Of Myosin 1a/6 Double Mutant MiceHoekstra N, Mark M, Ameen N. Normalization Of CFTR Brush Border Membrane Trafficking Defects In The Intestines Of Myosin 1a/6 Double Mutant Mice. The FASEB Journal 2012, 26: 885.1-885.1. DOI: 10.1096/fasebj.26.1_supplement.885.1.
- CFTR is Necessary for Vacuolar ATPase Proton Pump (VATPase) Localization and Function in Polarized Intestinal CaCo2BBe CellsCollaco A, Geibel P, Geibel J, Ameen N. CFTR is Necessary for Vacuolar ATPase Proton Pump (VATPase) Localization and Function in Polarized Intestinal CaCo2BBe Cells. Gastroenterology 2011, 140: s-645. DOI: 10.1016/s0016-5085(11)62673-5.
- T1837 The Vacuolar ATPase Associates With CFTR in Apical Endocytic and Recycling Vesicles and Undergoes cAMP Regulated Trafficking in Intestinal Epithelial CellsCollaco A, Jakab R, Gorelick F, Ameen N. T1837 The Vacuolar ATPase Associates With CFTR in Apical Endocytic and Recycling Vesicles and Undergoes cAMP Regulated Trafficking in Intestinal Epithelial Cells. Gastroenterology 2010, 138: s-589. DOI: 10.1016/s0016-5085(10)62715-1.
- T1862 Bicarbonate-Secreting NBCe1/CFTR Co-Expressing Villus Enterocytes Function to Expand the Condensed Intestinal Mucus Secreted by NKCC1 Expressing Goblet CellsJakab R, Ameen N. T1862 Bicarbonate-Secreting NBCe1/CFTR Co-Expressing Villus Enterocytes Function to Expand the Condensed Intestinal Mucus Secreted by NKCC1 Expressing Goblet Cells. Gastroenterology 2010, 138: s-594. DOI: 10.1016/s0016-5085(10)62740-0.
- T1744 Cell-Specific Functional Expression and Regulation of cAMP, Calcium and Acid-Stimulated Chloride and Bicarbonate Secretion in the Proximal Small IntestineJakab R, Collaco A, Ameen N. T1744 Cell-Specific Functional Expression and Regulation of cAMP, Calcium and Acid-Stimulated Chloride and Bicarbonate Secretion in the Proximal Small Intestine. Gastroenterology 2009, 136: a-570-a-571. DOI: 10.1016/s0016-5085(09)62625-1.
- S1771 Regulated Exocytosis and Fusion of Vesicle Associated CFTR to the Apical Plasma Membrane of the Intestine Is Mediated By the Snare Protein Syntaxin-3Ameen N, Collaco A. S1771 Regulated Exocytosis and Fusion of Vesicle Associated CFTR to the Apical Plasma Membrane of the Intestine Is Mediated By the Snare Protein Syntaxin-3. Gastroenterology 2008, 134: a-266. DOI: 10.1016/s0016-5085(08)61239-1.
- 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. PMID: 15667623, DOI: 10.1111/j.1399-3046.2005.00254.x.
- cAMP regulates the number of CFTR channels on the cell surface of rat small intestinal epithelium by exocytosisAmeen N, Salas P. cAMP regulates the number of CFTR channels on the cell surface of rat small intestinal epithelium by exocytosis. Gastroenterology 2001, 120: a310. DOI: 10.1016/s0016-5085(08)81541-7.
- Anomalous apical plasma membrane phenotype in CK8-deficient mice indicates a novel role for intermediate filaments in the polarization of simple epitheliaAmeen N, Figueroa Y, Salas P. 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: 563-575. PMID: 11171325, DOI: 10.1242/jcs.114.3.563.
- Subcellular distribution of CFTR in rat intestine supports a physiologic role for CFTR regulation by vesicle trafficAmeen N, van Donselaar E, Posthuma G, de Jonge H, McLaughlin G, Geuze H, Marino C, Peters P. Subcellular distribution of CFTR in rat intestine supports a physiologic role for CFTR regulation by vesicle traffic. Histochemistry And Cell Biology 2000, 114: 219-228. PMID: 11083465, DOI: 10.1007/s004180000167.
- Cellular localization of the cystic fibrosis transmembrane conductance regulator in mouse intestinal tractAmeen 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. PMID: 10959824, DOI: 10.1007/s004180000164.
- Distribution of CFTR in mouse small intestine differs from human and ratAmeen N, Salas P. Distribution of CFTR in mouse small intestine differs from human and rat. Gastroenterology 2000, 118: a1115. DOI: 10.1016/s0016-5085(00)80267-x.
- Microvillus Inclusion Disease: A Genetic Defect Affecting Apical Membrane Protein Traffic in Intestinal EpitheliumAmeen N, Salas P. Microvillus Inclusion Disease: A Genetic Defect Affecting Apical Membrane Protein Traffic in Intestinal Epithelium. Traffic 2000, 1: 76-83. PMID: 11208062, DOI: 10.1034/j.1600-0854.2000.010111.x.
- CFTR channel insertion to the apical surface in rat duodenal villus epithelial cells is upregulated by VIP in vivo.Ameen N, Martensson B, Bourguinon L, Marino C, Isenberg J, McLaughlin G. 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. PMID: 10036238, DOI: 10.1242/jcs.112.6.887.
- 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. Journal Of Clinical Investigation 1996, 98: 1304-1312. PMID: 8823295, PMCID: PMC507556, DOI: 10.1172/jci118917.
- A unique subset of rat and human intestinal villus cells express the cystic fibrosis transmembrane conductance regulatorAmeen N, Ardito T, Kashgarian M, Marino C. A unique subset of rat and human intestinal villus cells express the cystic fibrosis transmembrane conductance regulator. Gastroenterology 1995, 108: 1016-1023. PMID: 7535272, DOI: 10.1016/0016-5085(95)90198-1.