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
Education
Medical School
St. George's University of London
2009
London
England
Residency
Massachusetts General Hospital
2013
Boston
MA
Fellowship
Boston Children's Hospital
2016
Boston
MA
Publications
Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes. NPJ Genom Med. 2024 Dec 02; 9(1):60. View Abstract
Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair. Cell. 2024 Dec 26; 187(26):7533-7550.e23. View Abstract
Overcoming problematic growth phenotypes in organoids from patients with monogenic GI disease. PLoS One. 2024; 19(11):e0309072. View Abstract
ViCE: An automated and quantitative program to assess intestinal tissue morphology. J Pathol Inform. 2024 Dec; 15:100397. View Abstract
A MERFISHing Expedition for Colitis. Gastroenterology. 2024 Nov; 167(6):1239-1240. View Abstract
Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review. Am J Clin Nutr. 2024 07; 120(1):17-33. View Abstract
WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production. Cell Mol Gastroenterol Hepatol. 2024; 18(2):101349. View Abstract
Modeling the cell biology of monogenetic intestinal epithelial disorders. J Cell Biol. 2024 07 01; 223(7). View Abstract
Holding Back the Tide: Interferon-gamma to the Rescue. Gastroenterology. 2024 06; 166(6):1191-1192. View Abstract
Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease. J Clin Invest. 2023 10 16; 133(20). View Abstract
A Roadmap for the Human Gut Cell Atlas. Nat Rev Gastroenterol Hepatol. 2023 09; 20(9):597-614. View Abstract
Perspectives of Rare Disease Experts on Newborn Genome Sequencing. JAMA Netw Open. 2023 05 01; 6(5):e2312231. View Abstract
WNT2B Deficiency Causes Increased Susceptibility to Colitis in Mice and Impairs Intestinal Epithelial Development in Humans. bioRxiv. 2023 Apr 22. View Abstract
Therapy Development for Microvillus Inclusion Disease using Patient-derived Enteroids. bioRxiv. 2023 Jan 29. View Abstract
Gasdermin D pore-forming activity is redox-sensitive. Cell Rep. 2023 01 31; 42(1):112008. View Abstract
The Immune Ghosts of Pandemics Past. Gastroenterology. 2023 04; 164(4):696. View Abstract
The genetics of monogenic intestinal epithelial disorders. Hum Genet. 2023 May; 142(5):613-654. View Abstract
Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection. Cell. 2022 10 27; 185(22):4190-4205.e25. View Abstract
The epithelial-specific ER stress sensor ERN2/IRE1ß enables host-microbiota crosstalk to affect colon goblet cell development. J Clin Invest. 2022 09 01; 132(17). View Abstract
Disrupting Polarized Trafficking in Intestinal Epithelial Cells: Insights From a Novel Congenital Enteropathy Gene. Gastroenterology. 2022 09; 163(3):777. View Abstract
Membrane Lipids in Epithelial Polarity: Sorting out the PIPs. Front Cell Dev Biol. 2022; 10:893960. View Abstract
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 06 01; 46(6):846-853. View Abstract
Minimally Invasive Image-Guided Gut Transport Function Measurement Probe. Front Phys. 2021 Sep; 9. View Abstract
Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. Cell. 2021 08 19; 184(17):4495-4511.e19. View Abstract
Pycro-Manager: open-source software for customized and reproducible microscope control. Nat Methods. 2021 03; 18(3):226-228. View Abstract
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
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
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
IRE1ß negatively regulates IRE1a signaling in response to endoplasmic reticulum stress. J Cell Biol. 2020 Feb 03; 219(2). View Abstract
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
Drug Screen Identifies Leflunomide for Treatment of Inflammatory Bowel Disease Caused by TTC7A Deficiency. Gastroenterology. 2020 03; 158(4):1000-1015. View Abstract
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
INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling. Elife. 2018 10 25; 7. View Abstract
Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations. Am J Hum Genet. 2018 07 05; 103(1):131-137. View Abstract
Advances in Evaluation of Chronic Diarrhea in Infants. Gastroenterology. 2018 Jun; 154(8):2045-2059.e6. View Abstract
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
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
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
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
Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W. Front Physiol. 2015; 6:179. View Abstract
Altered goblet cell differentiation and surface mucus properties in Hirschsprung disease. PLoS One. 2014; 9(6):e99944. View Abstract
Discovery and development of antisecretory drugs for treating diarrheal diseases. Clin Gastroenterol Hepatol. 2014 Feb; 12(2):204-9. View Abstract
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
Airway surface liquid depth imaged by surface laser reflectance microscopy. J Gen Physiol. 2010 Sep; 136(3):353-62. View Abstract
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
Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis. Gut. 2007 Nov; 56(11):1529-35. View Abstract
Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching. Nat Methods. 2006 Apr; 3(4):275-80. View Abstract
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
New drug targets for cholera therapy. Trends Pharmacol Sci. 2005 Apr; 26(4):172-5. View Abstract
Submucosal gland dysfunction as a primary defect in cystic fibrosis. FASEB J. 2005 Mar; 19(3):431-3. View Abstract
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
Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor. Gastroenterology. 2004 Feb; 126(2):511-9. View Abstract
CFTR pharmacology and its role in intestinal fluid secretion. Curr Opin Pharmacol. 2003 Dec; 3(6):594-9. View Abstract
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
Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Am J Physiol Cell Physiol. 2003 Jan; 284(1):C2-15. View Abstract
Progesterone stimulation of fluid absorption by the rat uterine gland. Reproduction. 2002 May; 123(5):633-8. View Abstract
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
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
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
In vivo fluorescence measurement of Na(+) concentration in the pericryptal space of mouse descending colon. Am J Physiol Cell Physiol. 2001 Dec; 281(6):C1898-903. View Abstract
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
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