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Work from the Murphy Lab’s Aging Team featured in Nature!

What’s the secret to living to 100? Centenarian stem cells could offer clues

A bank of cells from people more than 100 years old gives scientists a new resource for studying longevity

Click here to read | By Smriti Mallapaty
read more

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Global Biopharma Giant GSK and BU Announce Collaboration to Pioneer New Lung Disease Treatments

Linkup aims to drive research into pulmonary fibrosis, a disease with no cure | Click here to read

The Brink | By Andrew Thurston | Photos by Cydney Scott

October 17, 2024

  • Publications

A specialized population of monocyte-derived tracheal macrophages promote airway epithelial regeneration through a CCR2-dependent mechanism

Publication from the Murphy Lab: Click here to read the article.

Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.

 

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Welcome to CReM

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The Alysandratos Lab’s mission is to advance our understanding of the inception of pulmonary fibrosis and identify druggable targets, with a specific focus on the alveolar epithelium. We believe that the poorly understood pathogenesis of pulmonary fibrosis, in part due to the lack of reliable human disease models, has been a major hurdle in developing effective therapies. To tackle this, we use patient-derived pluripotent stem cells (PSCs) to study the role of alveolar epithelial cells in initiating and perpetuating the fibrotic cascade with a goal of developing effective mechanistic therapies.

The Alysandratos Lab has openings for postdoctoral fellows – highly qualified applicants are encouraged to contact Dr. Alysandratos at kalysa@bu.edu for more information.

The Vanuytsel Lab’s mission is to find better solutions for patients suffering from blood disorders.

To accomplish this, we (1) generate red blood cells from sickle cell disease patient-specific induced pluripotent stem cells (iPSCs) to assess novel therapeutic options across the diverse patient population served here at Boston Medical Center; and (2) study hematopoietic development and the biology of blood stem cells to improve hematopoietic stem cell transplantation outcomes.

Here, our focus is on enhancing stem cell functionality rather than pure expansion of HSCs and we combine multi-parameter spectral flow cytometry, single cell omics and xenotransplantation assays to understand how expression profiles intersect with stem cell function. We also use these tools to map the subtle differences in hematopoietic stem cells throughout development, across mobilization regimens, and in the context of sickle cell disease.

The Wilson lab is focused on two major aspects of regenerative medicine:

1) Developing gene therapy approaches for the study and treatment of lung diseases: The ability to manipulate gene expression in specified lung cell populations has both experimental and therapeutic potential for lung disease. By developing viral vectors that transduce specific lung cell types in vivo, we hope to minimize potential off-target effects while maximizing our ability to target diseased cell populations. We work with lentiviral and AAV vectors to overexpress or knockdown expression of genes important to disease pathogenesis in the lung.

2) Utilizing induced pluripotent stem cells (iPSC) to study human lung and liver diseases: The Wilson lab is interested in the application of patient-derived iPS cells for the study of lung and liver diseases, such as alpha-1 antitrypsin deficiency (AATD).

The Hawkins Lab is interested in how the human lung develops and responds to injury to better understand human lung disease. Induced pluripotent stem cells (iPSCs) offer a unique opportunity to model human lung disease and bridge the gap between research in animal models and humans.

Using this iPSC platform, we are focused on understanding the molecular mechanisms that control human lung development. We hope to apply this knowledge to advance our understanding of and develop precision medicine approaches for lung disease.

The Murphy laboratory is composed of dynamic and passionate researchers who utilize multiple stem cell-based platforms to answer basic biological questions and combat disease. Central directions of the laboratory include: developmental hematopoiesis, the modeling of blood-borne disease, and discovery and therapeutic intervention in sickle cell disease, amyloidosis, and aging.

The Murphy Lab has pioneered: The world’s largest sickle cell disease-specific iPSC library and platforms and protocols that can used to recapitulate hematopoietic ontogeny and to develop and validate novel therapeutic strategies for the disease; The successful modeling of a protein folding disorder called familial amyloidosis demonstrating the ability to model a long-term, complex, multisystem disease in a relatively short time, using lineage-specified cells (hepatic, cardiac and neuronal) derived from patient-specific stem cells; The first iPSC library created from subjects with exceptional longevity (centenarians) that serves as an unlimited resource of biomaterials to fuel the study of aging and the development of novel therapeutics for aging-related disease.

www.murphylaboratory.com

@DRGJMurphy

The Serrano Lab studies neurodevelopment and cardiovascular development in the context of rare multi-systemic disorders originated by pathogenic variants in epigenetic modifiers like KMT2D.  

We aim to identify shared molecular and cellular mechanisms driving cardiovascular and brain development with particular interest in cell differentiation, migration, and cell cycle progression.  

Our lab combines rare disease modeling in zebrafish together with cardiovascular and neurobiology techniques and human iPSC-derived brain organoids and endothelial cells.  

We believe that a patient-forward focus to our projects will help us to get better understanding of disease mechanisms through basic science research. To this end, we are active in the collaborative community among field experts and rare disease patient-advocacy groups who drive our research program to identify therapeutic targets in patient-specific iPS cells. 

The Mostoslavsky Lab is a basic science laboratory in the Section of Gastroenterology in the Department of Medicine at Boston University.

Our goal is to advance our understanding of stem cell biology with a focus on their genetic manipulation via gene transfer and their potential use for stem cell-based therapy.

The Mostoslavsky’s Lab designed and constructed the STEMCCA vector for the generation of iPS cells, a tool that has become the industry standard for nuclear reprogramming. Project areas in the lab focuses on the use of different stem cell populations, including embryonic stem cells, induced Pluripotent Stem (iPS) cells, hematopoietic stem cells and intestinal stem cells and their genetic manipulation by lentiviral vectors.

Our laboratory have already established a large library of disease-specific iPS cells with a particular interest in utilizing iPS cells to model diseases of the liver, the gastrointestinal tract, prion-mediated neurodegenerative diseases and immune-based inflammatory conditions, using iPSC-derived microglia, macrophages and T/NK cells.

The Gouon-Evans lab investigates cellular and molecular mechanisms driving liver development, regeneration and cancer. We specifically interrogate the role of progenitor/stem cells and how they share similar molecular signature and functions during these 3 processes.

Our innovative tools include: 1) directed differentiation of human pluripotent stem cells (PSC) to generate in vitro liver progenitors and their derivative hepatocytes, the main functional cell type of the liver, 2) mouse models with lineage tracing strategy to track in vivo the fate of progenitor cells, 3) PSC derivative cell transplantation into mouse models with damaged livers as cell therapy for liver diseases, 3) dissection of liver cancer specimens from patients to identify and define the impact of specific cancer stem cells in liver oncogenesis.

Projects in the Gouon-Evans lab will lead to a better understanding of the liver development, to the establishment of multi-modular approaches for improving liver regeneration with PSC derivatives, and will reveal the impact of specific cancer stem cells as a target for diagnosis and therapy in liver oncogenesis.

Our research focuses on understanding how lung epithelial progenitors interact with their supportive niche in the contexts of pulmonary disease and repair. We use cell culture, mouse models, and cell engraftment to study and augment these interactions with the ultimate goal of establishing novel therapies for pulmonary disease.

In addition, it is our mission to foster a welcoming and supportive environment, both within our lab and the wider research community, in order to train the next generation of scientists. We strongly believe that a diverse and collaborative community is an essential foundation for exploring the world around us and developing effective treatments for patients.