ABOUT THE RESEARCHER

OVERVIEW

Lab website: http://www.thiagarajahlab.com

Research in the lab aims to understand how the intestinal epithelium senses and interacts with its surroundings and how epithelial membrane channels and transporters contribute to immune function, host-microbial symbiosis, and cellular metabolism. Research projects in the lab use a variety of approaches and span several aspects of intestinal physiology and disease, including both basic science and translational research.

Specific projects include:

  • The role of hydrogen peroxide in epithelial cell pattern recognition receptor signaling
  • Developing therapies for Microvillus Inclusion Disease
  • The role of TTC7A in epithelial lumen formation

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy. Am J Surg Pathol. 2022 Jan 05. View abstract
  2. Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. Cell. 2021 08 19; 184(17):4495-4511.e19. View abstract
  3. Pycro-Manager: open-source software for customized and reproducible microscope control. Nat Methods. 2021 03; 18(3):226-228. View abstract
  4. Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis. Eur J Hum Genet. 2021 06; 29(6):998-1007. View abstract
  5. Extracellular cyclic dinucleotides induce polarized responses in barrier epithelial cells by adenosine signaling. Proc Natl Acad Sci U S A. 2020 11 03; 117(44):27502-27508. View abstract
  6. NOX1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset IBD and NOX1 Deficiency. Inflamm Bowel Dis. 2020 07 17; 26(8):1166-1176. View abstract
  7. IRE1ß negatively regulates IRE1a signaling in response to endoplasmic reticulum stress. J Cell Biol. 2020 Feb 03; 219(2). View abstract
  8. A quantitative single-cell assay for retrograde membrane traffic enables rapid detection of defects in cellular organization. Mol Biol Cell. 2020 03 19; 31(7):511-519. View abstract
  9. Drug Screen Identifies Leflunomide for Treatment of Inflammatory Bowel Disease Caused by TTC7A Deficiency. Gastroenterology. 2020 03; 158(4):1000-1015. View abstract
  10. Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea. JCI Insight. 2019 02 21; 4(4). View abstract
  11. An Intravenous Fish Oil-Based Lipid Emulsion Successfully Treats Intractable Pruritus and Cholestasis in a Patient with Microvillous Inclusion Disease. Hepatology. 2019 03; 69(3):1353-1356. View abstract
  12. INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling. Elife. 2018 10 25; 7. View abstract
  13. Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations. Am J Hum Genet. 2018 07 05; 103(1):131-137. View abstract
  14. Advances in Evaluation of Chronic Diarrhea in Infants. Gastroenterology. 2018 Jun; 154(8):2045-2059.e6. View abstract
  15. Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia. Proc Natl Acad Sci U S A. 2017 01 17; 114(3):568-573. View abstract
  16. The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion. Oncogene. 2017 03 30; 36(13):1816-1828. View abstract
  17. Microbial sphingomyelinase induces RhoA-mediated reorganization of the apical brush border membrane and is protective against invasion. Mol Biol Cell. 2016 Apr 01; 27(7):1120-30. View abstract
  18. CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation. Cell Mol Gastroenterol Hepatol. 2016 May; 2(3):317-327. View abstract
  19. Secretory diarrhoea: mechanisms and emerging therapies. Nat Rev Gastroenterol Hepatol. 2015 Aug; 12(8):446-57. View abstract
  20. Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W. Front Physiol. 2015; 6:179. View abstract
  21. Altered goblet cell differentiation and surface mucus properties in Hirschsprung disease. PLoS One. 2014; 9(6):e99944. View abstract
  22. Discovery and development of antisecretory drugs for treating diarrheal diseases. Clin Gastroenterol Hepatol. 2014 Feb; 12(2):204-9. View abstract
  23. Chloride channel inhibition by a red wine extract and a synthetic small molecule prevents rotaviral secretory diarrhoea in neonatal mice. Gut. 2014 Jul; 63(7):1120-9. View abstract
  24. Chloride channel-targeted therapy for secretory diarrheas. Curr Opin Pharmacol. 2013 Dec; 13(6):888-94. View abstract
  25. Response to "Diffusion versus convection". J Gen Physiol. 2013 Aug; 142(2):173. View abstract
  26. Convective washout reduces the antidiarrheal efficacy of enterocyte surface-targeted antisecretory drugs. J Gen Physiol. 2013 Feb; 141(2):261-72. View abstract
  27. CFTR inhibitors. Curr Pharm Des. 2013; 19(19):3529-41. View abstract
  28. CFTR inhibitors for treating diarrheal disease. Clin Pharmacol Ther. 2012 Sep; 92(3):287-90. View abstract
  29. Airway surface liquid depth imaged by surface laser reflectance microscopy. J Gen Physiol. 2010 Sep; 136(3):353-62. View abstract
  30. Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. FASEB J. 2010 Nov; 24(11):4178-86. View abstract
  31. Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis. Gut. 2007 Nov; 56(11):1529-35. View abstract
  32. Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching. Nat Methods. 2006 Apr; 3(4):275-80. View abstract
  33. Noninvasive early detection of brain edema in mice by near-infrared light scattering. J Neurosci Res. 2005 Apr 15; 80(2):293-9. View abstract
  34. New drug targets for cholera therapy. Trends Pharmacol Sci. 2005 Apr; 26(4):172-5. View abstract
  35. Submucosal gland dysfunction as a primary defect in cystic fibrosis. FASEB J. 2005 Mar; 19(3):431-3. View abstract
  36. A small molecule CFTR inhibitor produces cystic fibrosis-like submucosal gland fluid secretions in normal airways. FASEB J. 2004 May; 18(7):875-7. View abstract
  37. Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor. Gastroenterology. 2004 Feb; 126(2):511-9. View abstract
  38. CFTR pharmacology and its role in intestinal fluid secretion. Curr Opin Pharmacol. 2003 Dec; 3(6):594-9. View abstract
  39. Sodium and chloride concentrations, pH, and depth of airway surface liquid in distal airways. J Gen Physiol. 2003 Nov; 122(5):511-9. View abstract
  40. Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. . 2003 Jan; 284(1):C2-15. View abstract
  41. Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J Clin Invest. 2002 Dec; 110(11):1651-8. View abstract
  42. Progesterone stimulation of fluid absorption by the rat uterine gland. Reproduction. 2002 May; 123(5):633-8. View abstract
  43. Aquaporin deletion in mice reduces corneal water permeability and delays restoration of transparency after swelling. J Biol Chem. 2002 May 24; 277(21):19139-44. View abstract
  44. Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by transforming growth factor beta and angiotensin II. BMC Gastroenterol. 2002; 2:4. View abstract
  45. Chloride concentration in endosomes measured using a ratioable fluorescent Cl- indicator: evidence for chloride accumulation during acidification. J Biol Chem. 2002 Feb 15; 277(7):5506-13. View abstract
  46. In vivo fluorescence measurement of Na(+) concentration in the pericryptal space of mouse descending colon. . 2001 Dec; 281(6):C1898-903. View abstract
  47. Evidence of amiloride-sensitive fluid absorption in rat descending colonic crypts from fluorescence recovery of FITC-labelled dextran after photobleaching. J Physiol. 2001 Oct 15; 536(Pt 2):541-53. View abstract
  48. Radiation induced cytochrome c release causes loss of rat colonic fluid absorption by damage to crypts and pericryptal myofibroblasts. Gut. 2000 Nov; 47(5):675-84. View abstract