Alexandra Sontheimer-Phelps

ORCID: 0000-0003-4732-2835
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About
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Research Areas
  • 3D Printing in Biomedical Research
  • Cancer Cells and Metastasis
  • Gut microbiota and health
  • Probiotics and Fermented Foods
  • Innovative Microfluidic and Catalytic Techniques Innovation
  • Escherichia coli research studies
  • Microfluidic and Bio-sensing Technologies
  • Pancreatic function and diabetes
  • Retinoids in leukemia and cellular processes
  • Regulation of Appetite and Obesity
  • Clostridium difficile and Clostridium perfringens research
  • Inflammasome and immune disorders
  • Microfluidic and Capillary Electrophoresis Applications
  • Ion Channels and Receptors
  • Cardiovascular, Neuropeptides, and Oxidative Stress Research
  • Anatomy and Medical Technology
  • Diabetes Treatment and Management
  • Barrier Structure and Function Studies
  • Cancer Genomics and Diagnostics
  • Metabolism, Diabetes, and Cancer
  • Gastrointestinal motility and disorders
  • Pluripotent Stem Cells Research
  • Pancreatitis Pathology and Treatment
  • Pancreatic and Hepatic Oncology Research
  • Infant Health and Development

Harvard University
2014-2022

Beth Israel Deaconess Medical Center
2014-2020

University of Freiburg
2017-2019

Inspire
2019

Harvard University Press
2019

Massachusetts General Hospital
2015

Abstract Here we describe a method for fabricating primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The are expanded as 3D organoids, dissociated, and cultured on porous membrane within microfluidic device with microvascular endothelium in parallel microchannel under flow cyclic deformation. In the Intestine Chip, epithelium forms villi-like projections lined by polarized that undergo multi-lineage...

10.1038/s41598-018-21201-7 article EN cc-by Scientific Reports 2018-02-07

Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) recapitulate organ microenvironment-specific growth, tumor dormancy, and responses tyrosine kinase inhibitor (TKI) therapy observed patients vivo. Use the mechanical actuation functionalities this revealed a previously unknown sensitivity invasion, TKI therapeutic physical cues associated with breathing motions,...

10.1016/j.celrep.2017.09.043 article EN cc-by-nc-nd Cell Reports 2017-10-01

Background & AimsThe mucus layer in the human colon protects against commensal bacteria and pathogens, defects its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. However, our understanding of physiology is limited by lack vitro models that replicate colonic function. Here, we investigated if combining organ-on-a-chip organoid technologies can be leveraged develop a human-relevant model physiology.MethodsA colon-on-a-chip (Colon Chip) microfluidic...

10.1016/j.jcmgh.2019.11.008 article EN cc-by-nc-nd Cellular and Molecular Gastroenterology and Hepatology 2019-11-26

Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice relatively resistant this pathogen. This intrinsic species-specific difference EHEC limits translation murine research human. Furthermore, studying mechanisms underlying differential is a difficult problem due complex vivo interactions between host, pathogen, and disparate commensal microbial communities. We utilize...

10.1186/s40168-019-0650-5 article EN cc-by Microbiome 2019-03-20

Significance There is a growing need for insulin-sensitizing therapies to treat type 2 diabetes (T2D). In obese T2D humans, NLRP3 inflammasome activation contributes insulin resistance. Serum levels of retinol binding protein 4 (RBP4) are elevated in obese, insulin-resistant humans and RBP4 SNPs that increase adipose expression confer greater risk. correlate with many metabolic syndrome-related components, including cardiovascular disease. elevation induces resistance mice by increasing...

10.1073/pnas.2013877117 article EN Proceedings of the National Academy of Sciences 2020-11-19

Pancreatic duct glands (PDGs) have molecular features known to mark stem cell niches, but their function remains be determined. To investigate the role of PDGs as a progenitor niche, were analyzed in both humans and mice. Cells characterized by immunohistochemistry microarray analysis. In vivo proliferative activity migration PDG cells evaluated using BrdU tag-and-chase strategy mouse model pancreatitis. vitro assays used determine trefoil factor (TFF) -1 2 migration. Proliferative...

10.1016/j.scr.2015.05.006 article EN cc-by-nc-nd Stem Cell Research 2015-06-06

Protein-tyrosine phosphatase 1B (PTP1B) regulates food intake (FI) and energy expenditure (EE) by inhibiting leptin signaling in the hypothalamus. In peripheral tissues, PTP1B insulin signaling, but its effects on CNS action are largely unknown. Mice harboring a whole-brain deletion of gene encoding (Ptpn1) lean, leptin-hypersensitive, resistant to high fat diet–induced (HFD-induced) obesity. Arcuate proopiomelanocortin (POMC) neuron–specific Ptpn1 causes similar, much milder, phenotype,...

10.1172/jci68585 article EN Journal of Clinical Investigation 2014-07-31

Here we describe of an ‘Interrogator’ instrument that uses liquid-handling robotics, a custom software package, and integrated mobile microscope to enable automated culture, perfusion, medium addition, fluidic linking, sample collection, in situ microscopic imaging up 10 Organ Chips inside standard tissue culture incubator. The Interrogator platform maintained the viability organ-specific functions 8 different vascularized, 2-channel, (intestine, liver, kidney, heart, lung, skin, blood-brain...

10.1101/569541 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2019-03-06

ABSTRACT Background Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans enterohemorrhagic E. coli (EHEC) whereas mice relatively resistant this pathogen. This intrinsic species-specific difference EHEC limits translation murine research human. Furthermore, studying mechanisms underlying differential is a difficult problem due complex vivo interactions between host, pathogen, and disparate commensal microbial communities. Results We...

10.1101/513614 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2019-01-07

ABSTRACT Background & Aims The mucus layer in the human colon protects against commensal bacteria and pathogens, defects its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. However, our understanding of physiology is limited by lack vitro models that replicate colonic function. Here, we investigated if combining organ-on-a-chip organoid technologies can be leveraged develop a human-relevant model physiology. Methods A colon-on-a-chip (Colon...

10.1101/740423 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2019-08-20
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