Alexandra Eicher
Alexandra Eicher
Postdoctoral Fellow
Dr. Oliver Pourquie's Lab
Brigham and Women's Hospital
Harvard Medical School
About Me
I am a developmental biologist currently working as a postdoctoral research fellow in Dr. Olivier Pourquie's lab at Brigham and Women's Hospital. I completed my Ph.D. in Molecular and Developmental Biology at Cincinnati Children’s Hospital Medical Center (CCHMC) and my B.S. in Biochemical Engineering at the University of New Hampshire.
My undergraduate research consisted of several bioengineering projects that honed my ability to mathematically model biological processes and design novel tools to better study intricate biology. My Ph.D. work in Dr. James Wells’ lab at CCHMC applied my engineering and design skills to the field of translational and regenerative medicine. My goal was to engineer novel human model systems, derived from pluripotent stem cells, to study the development and dysfunction of the enteric nervous system (ENS).
My broader research interests involve understanding how mechanical forces of development control not only collective cellular migration and morphogenesis but also downstream transcriptional regulation. During my post-doctoral training, I plan to learn computational modeling skills that I can use to investigate these biophysical forces on systems biology level.
Ph.D. Thesis Research
Using Stem Cell Technologies to Engineer Complex Human Model Systems
Engineering Novel Human Model Systems
In Dr. James Wells’ lab at Cincinnati Children's, I engineered Human Gastric Organoids (HGOs) with a functional enteric nervous system (ENS) to study its development and dysfunction. We accomplish this by applying signaling pathways known to control human organ development to the directed differentiation of human pluripotent stem cells (hPSCs) into both endoderm- and ectoderm-derived lineages. This image is a whole-mount immunostaining of HGOs (white) with incorporated neurons (red).
Enteric-Mesenchymal Crosstalk in the Developing Stomach
We used our novel innervated HGOs to investigate the specific molecular and cellular roles the ENS plays on the developing gastric and esophageal mesenchyme. Evidence in chick embryos suggests the ENS is required for proper patterning and differentiation of the gastric mesenchyme (Faure S. 2015). This image shows an HGO with three organized layers: an epithelium (white) surrounded by mesenchyme (red) and neurons (green).
Development and Dysfunction of the Proximal ENS
We used both human and mouse models systems to study both the normal and perturbed development of the enteric nervous system (ENS). We focused on the early migration of ENS progenitors, known as neural crest cells (NCCs), into the developing foregut as well the roles the ENS plays on adult esophageal and gastric motility. This image shows NCCs (green) migrating into an e9.5 murine foregut (white).
Previous Research
In Industrial and Academic Bioengineering
Bioengineering yeast to improve corn-ethanol yields
As a Bioprocess Research Associate at Mascoma, LCC., an R&D company focused on improving corn-ethanol yield by genetically-modifying proprietary yeast strains, I designed and operated several novel fermentation assays to assess the efficacy of newly engineered yeast strains. I also established efficient and reliable quantification methods, such as near-infrared spectroscopy and kinetic ethanol assays, to determine the early kinetics of each strain’s fermentation dynamics.
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Image Credit: Mogana Das Murtey and Patchamuthu Ramasamy/CC BY-SA 3.0
Fellowships
F31 - Development and Disease of the Human Proximal Enteric Nervous System
Awarded by NIDDK on July 16, 2018
Despite the many people suffering from enteric motility disorders, virtually nothing is known about how the proximal ENS forms so this proposal seeks to build a molecular and cellular framework for proximal ENS migration, assembly, and integration into foregut tissues. We aim to 1) map the molecular and cellular architecture of the proximal ENS, 2) identify mesenchymal signals that control proximal ENS development, and 3) generate human foregut tissues with a functional ENS.
Publications
Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells
Published in Cell Stem Cell on January 6, 2022
Eicher AK, Kechele DO, Sundaram N, Berns HM, Poling HM, Haines LE, Sanchez JG, Kishimoto K, Krishnamurthy M, Han L, Zorn AM, Helmrath MA, and Wells JM
doi: 10.1016/j.stem.2021.10.010
We developed an organoid assembly approach starting with cells from the three primary germ layers—enteric neuroglial, mesenchymal, and epithelial precursors—that were derived separately from human pluripotent stem cells (PSCs). From these three cell types, we generated human antral and fundic gastric tissue containing differentiated glands surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered antral tissue.
Translating Developmental Principles to Generate Human Gastric Organoids
Published in CMGH on January 31, 2018
Eicher AK, Berns HM, and Wells JM
doi:10.1016/j.jcmgh.2017.12.014
This review discusses the basics of stomach morphology, function, and developmental pathways involved in generating HGOs. We also highlight important gaps in our understanding of how epithelial and mesenchymal interactions are essential for the development and overall function of the human stomach.
Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis
Published in Nature Communications on August 27, 2020
Han L, Chaturvedi P, Kishimoto K, Koike H, Nasr T, Iwasawa K, Giesbrecht K, Witcher PC, Eicher A, Haines L, Lee Y, Shannon JM, Morimoto M, Wells JM, Takebe T, and Zorn AM
doi: 10.1038/s41467-020-17968-x
Here, we use single cell transcriptomics to generate a high-resolution cell state map of the embryonic mouse foregut. This identifies a diversity of SM cell types that develop in close register with the organ-specific epithelium. We infer a spatiotemporal signaling network of endoderm-mesoderm interactions that orchestrate foregut organogenesis. We validate key predictions with mouse genetics, showing the importance of endoderm-derived signals in mesoderm patterning. Finally, leveraging these signaling interactions, we generate different SM subtypes from human pluripotent stem cells (hPSCs), which previously have been elusive.
Education
2015 -Â 2021
Ph.D. in Molecular and Developmental Biology
College of Medicine
University of Cincinnati
Cincinnati, OH
2009-2013
B.S. in Chemical Engineering: Bioengineering
College of Engineering and Physical Sciences
University of New Hampshire
Durham, NH
Contact Me
Thank you for your interest in my research. Please feel free to get in touch with any questions or comments you may have regarding my work and publications.
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Below are some pictures showcasing my lab and friends at CCHMC.
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