Finn Hawkins

Finn Hawkins
Boston University | BU · Pulmonary Center

MB. BCh.

About

62
Publications
6,176
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2,305
Citations

Publications

Publications (62)
Article
Full-text available
The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mes...
Article
There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We presen...
Article
Full-text available
Airway basal cells play an essential role in the maintenance of the airway epithelium. Here, we provide a detailed directed differentiation protocol to generate ‘‘induced basal cells (iBCs)’’ from human pluripotent stem cells. iBCs recapitulate biological and functional properties of airway basal cells including mucociliary differentiation in vitro...
Preprint
There is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We presen...
Article
Full-text available
Primary pulmonary extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), also known as bronchus-associated lymphoid tissue (BALT lymphoma), is the most common primary pulmonary lymphoma but is rare (<1%) among all non-Hodgkin lymphomas and among pulmonary neoplasms in general. We herein report the case of a 59-year...
Preprint
Cystic fibrosis (CF) is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane regulator (CFTR) anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of the CFTR channel using established animal and cell-based models led to the recent discovery of effective CFTR modulators...
Preprint
Full-text available
The extensive crosstalk between the developing heart and lung is pivotal for their proper morphogenesis and maturation. However, there remains a lack of model systems for investigating the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing simultaneous induction of both...
Article
The derivation of tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would have broad reaching implications for regenerative medicine. Here, we report the directed differentiation of human iPSCs into airway basal cells (“iBCs”), a population resembling the stem cell of the airway epithelium. Using a dual fluorescent report...
Article
A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here, we present an in vitro human model that simu...
Article
Cystic fibrosis (CF) is an autosomal recessive disease caused by variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although CF affects multiple organs, the primary cause of mortality is respiratory failure resulting from poor clearance of hyperviscous secretions and subsequent airway infection. Recently developed CF...
Preprint
Full-text available
The most severe and fatal infections with SARS-CoV-2 result in the acute respiratory distress syndrome, a clinical phenotype of coronavirus disease 2019 (COVID-19) that is associated with virions targeting the epithelium of the distal lung, particularly the facultative progenitors of this tissue, alveolar epithelial type 2 cells (AT2s). Little is k...
Preprint
Full-text available
Development of an anti-SARS-CoV-2 therapeutic is hindered by the lack of physiologically relevant model systems that can recapitulate host-viral interactions in human cell types, specifically the epithelium of the lung. Here, we compare induced pluripotent stem cell (iPSC)-derived alveolar and airway epithelial cells to primary lung epithelial cell...
Chapter
There was significant progress over the last decade in the ability to generate induced pluripotent stem cell (iPSC)-derived airway organoids. We and others have developed step-wise, directed differentiation protocols to recapitulate the key milestones in human airway development, generating iPSC-derived airway organoids that possess the major human...
Preprint
Full-text available
The derivation of self-renewing tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would shorten the time needed to engineer mature cell types in vitro and would have broad reaching implications for the field of regenerative medicine. Here we report the directed differentiation of human iPSCs into putative airway basal cel...
Article
MicroRNAs that are overexpressed in cystic fibrosis (CF) bronchial epithelial cells (BEC) negatively regulate CFTR and nullify the beneficial effects of CFTR modulators. We hypothesized that it is possible to reverse microRNA-mediated inhibition of CFTR using CFTR-specific target site blockers (TSBs) and to develop a drug-device combination inhalat...
Article
Full-text available
Efficient generation of human induced pluripotent stem cell (hiPSC)-derived human intestinal organoids (HIOs) would facilitate the development of in vitro models for a variety of diseases that affect the gastrointestinal tract, such as inflammatory bowel disease or Cystic Fibrosis. Here, we report a directed differentiation protocol for the generat...
Article
Alveolar epithelial type II cells (AEC2s) are the facultative progenitors of lung alveoli and serve as the surfactant-producing cells of air-breathing organisms. Although primary human AEC2s are difficult to maintain stably in cell cultures, recent advances have facilitated the derivation of AEC2-like cells from human pluripotent stem cells (hPSCs)...
Article
Full-text available
The University of Vermont Larner College of Medicine, in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), the Alpha-1 Foundation, the American Thoracic Society, the Cystic Fibrosis Foundation, the European Respiratory Society, the International Society for Cell & Gene Therapy, and the Pulmonary Fibrosis Foundation, convened...
Conference Paper
Background Cystic fibrosis (CF) is one of the most common lethal genetic diseases and is caused by mutations in the CFTR gene where a deletion of phenylalanine at position 508 (F508del) accounts for the most prevalent mutation worldwide. MicroRNA (miRNA) are small non-coding RNAs that can regulate up to two thirds of gene expression in human cells...
Article
Full-text available
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the life-limiting hereditary disease, cystic fibrosis (CF). Decreased or absent functional CFTR protein in airway epithelial cells leads to abnormally viscous mucus and impaired mucociliary transport, resulting in bacterial infections and inflammation causing pro...
Article
Two recent studies have identified novel airway cells termed pulmonary ionocytes that express higher levels of CFTR than other airway cells express. These findings raise new questions in the evolving debate about the physiological role of CFTR in lung epithelia and its importance in the pathogenesis of cystic fibrosis (CF).
Data
Table S1. Table of All p Values Obtained by ANOVA with Tukey's Multiple Comparisons Test for Figures 2H, 4B, and 7G, Related to Figures 2, 4, and 7
Data
Table S2. Searchable Table of Analyzed Microarray Results with Statistical Analysis by One-Way ANOVA Comparing All Five Array Samples and Moderated Pairwise Student's t Tests to Compare Each Pair of Individual Samples for Each Gene, Related to Figure 3
Data
Table S3. Table of All Genes Upregulated (by ANOVA with FDR-Adjusted p < 0.05; Variance > 3) in Clusters from Analysis in Figure 5. This List of Genes Is Represented in the Heatmap in Figure 5C, Related to Figure 5
Data
Table S4. Searchable Table of Analyzed Single-Cell RNA-Seq Data Showing Genes Differentially Expressed (FDR-Adjusted p < 0.1 by Negative Binomial Exact Test) in Each Cell Cluster, Related to Figure 6
Data
Table S5. List of Cell-Cycle Genes Included versus Excluded from Analysis of Single-Cell RNA-Seq Data to Test the Effect on Cell Clustering, Related to Figure 6
Article
Full-text available
Lung epithelial lineages have been difficult to maintain in pure form in vitro, and lineage-specific reporters have proven invaluable for monitoring their emergence from cultured pluripotent stem cells (PSCs). However, reporter constructs for tracking proximal airway lineages generated from PSCs have not been previously available, limiting the char...
Article
New protocols to efficiently generate functional airway epithelial organoids from human pluripotent stem cells (PSCs) would represent a major advance towards effective disease modeling, drug screening and cell based therapies for lung disorders. This unit describes an approach using stage‐specific signaling pathway manipulation to differentiate cel...
Article
The in vitro directed differentiation of pluripotent stem cells (PSCs) through stimulation of developmental signaling pathways can generate mature somatic cell types for basic laboratory studies or regenerative therapies. However, there has been significant uncertainty regarding how to separately derive lung vs. thyroid epithelial lineages, since t...
Article
Lung alveoli, which are unique to air-breathing organisms, have been challenging to generate from pluripotent stem cells (PSCs) in part because there are limited model systems available to provide the necessary developmental roadmaps for in vitro differentiation. Here we report the generation of alveolar epithelial type 2 cells (AEC2s), the faculta...
Article
Effective derivation of functional airway organoids from induced pluripotent stem cells (iPSCs) would provide valuable models of lung disease and facilitate precision therapies for airway disorders such as cystic fibrosis. However, limited understanding of human airway patterning has made this goal challenging. Here, we show that cyclical modulatio...
Conference Paper
Full-text available
Background. The directed differentiation of human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) into lung epithelial lineages offers the opportunity to study human lung development at time points previously inaccessible to researchers and has broad application for the study of lung diseases. Directed differentiation protoco...
Article
Full-text available
It has been postulated that during human fetal development, all cells of the lung epithelium derive from embryonic, endodermal, NK2 homeobox 1-expressing (NKX2-1+) precursor cells. However, this hypothesis has not been formally tested owing to an inability to purify or track these progenitors for detailed characterization. Here we have engineered a...
Article
Introduction Alpha-1 antitrypsin (AAT) deficiency (AATD) is the most frequent form of genetically determined emphysema. Type II alveolar cells (AEC2) are capable of producing AAT but little is known about their role in AATD pathogenesis. Aims and objectives We hypothesise that AEC2s play an intrinsic role in AATD pathogenesis and therefore we sough...
Chapter
This chapter reviews the current knowledge of the molecular mechanisms controlling embryonic lung development in animal models from the initial specification of a small number of respiratory progenitor cells in the ventral foregut endoderm through the formation of the mature adult lung with regionally specialized epithelial, interstitial, and vascu...
Article
Differentiation of functional thyroid epithelia from pluripotent stem cells (PSCs) holds the potential for application in regenerative medicine. However, progress toward this goal is hampered by incomplete understanding of the signaling pathways needed for directed differentiation without forced overexpression of exogenous transgenes. Here we use m...
Article
Full-text available
Recently developed reprogramming and genome editing technologies make possible the derivation of corrected patient-specific pluripotent stem cell sources – potentially useful for the development of new therapeutic approaches. The primary defect in Cystic Fibrosis (CF), an autosomal recessive disorder, is the regulation of epithelial chloride transp...
Article
Full-text available
Recently developed reprogramming and genome editing technologies make possible the derivation of corrected patient-specific pluripotent stem cell sources-potentially useful for the development of new therapeutic approaches. Starting with skin fibroblasts from patients diagnosed with cystic fibrosis, we derived and characterized induced pluripotent...
Article
Full-text available
The discovery of embryonic and induced pluripotent stem cells (ESCs and iPSCs) has ushered in an exciting new era of regenerative medicine. Human pluripotent stem cells can be "directed" in vitro toward lung epithelium by applying specific stepwise combinations of growth factors that recapitulate the molecular mechanisms of respiratory development...
Article
Two populations of Nkx2-1(+) progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived fr...
Article
A 30-year-old African American female (Patient # 1) with Hemoglobin SC (HbSC) disease presented with a 1 week history of progressive left flank and lower extremity pain with diffuse myalgias. She had a history of multiple prior vasoocclusive episodes requiring simple and exchange transfusions. At the time of admission on physical examination, she w...
Article
Chylothorax is an uncommon form of pleural effusion that can be associated with traumatic and nontraumatic causes. Optimal management and outcome for patients with chylothorax remain unclear. This retrospective single-center study assessed the modes of management for chylothorax in 74 adult patients (> or =18 years old) and associated outcomes. The...
Article
The aviation-medicine analogy provides an opportunity for a necessary debate pertaining to operational challenges within our current physician-training model. An important issue is the legitimate tension between sleep deprivation and comprehensive clinical experience (including the physician's ethos of selflessness and the continuity of patient car...
Article
To determine the biochemical parameters of chylous pleural fluids and better inform current clinical practice in the diagnosis of chylothorax. We retrospectively reviewed 74 patients with chylothorax (defined by the presence of chylomicrons) who underwent evaluation during a 10-year period from January 1, 1997, through December 31, 2006. The bioche...

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