About

Jeremy Binder Katzen, MD, is an Assistant Professor of Medicine in the Pulmonary, Allergy and Critical Care department at the University of Pennsylvania's Perelman School of Medicine. His clinical expertise includes Interstitial Lung Disease, Pulmonary Fibrosis, and Genetic Interstitial Lung Disease. His research focuses on lung epithelial biology, lung development, surfactant biology, cell stress, and lung fibrosis. Katzen has contributed to understanding the molecular and cellular mechanisms underlying pulmonary diseases, including the development of targeted therapies and innovative delivery methods such as DNA-LNPs and lipid nanoparticles. His work also explores the role of inflammatory fibroblasts, alveolar epithelial cell metabolism, and the cellular origins of fibrosis, with a particular interest in translational models for interstitial lung disease.

Research topics

• Biology
• Medicine
• Cell biology
• Pathology
• Immunology

Selected publications

• Targeting DNA‐LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity

  Advanced Science · 2026-01-20 · 1 citations

  articleOpen access

  DNA-lipid nanoparticles (DNA-LNPs) loaded with inhibitors of the cGAS-STING pathway enable safe and effective delivery of DNA in vivo. Herein, we report the first instances of extrahepatic DNA-LNP targeting. DNA-LNPs conjugated to antibodies against PECAM-1 or VCAM-1 target the endothelium of the lungs and brain/spleen, respectively. These LNPs drive robust transgene expression in their target organs, with greater magnitude and duration than untargeted LNPs. Lung specificity of PECAM-targeted transgene expression increases over two weeks, resulting in markedly higher lung-to-liver expression ratios than our previous PECAM-targeted mRNA-LNPs. Off-target liver DNA expression declines to undetectable levels but persists in the lungs, while mRNA expression uniformly decreases due to its short half-life. We further improve this expression specificity by replacing full-length antibodies with Fab fragments. Single-cell analysis reveals a key mechanism underlying the improvements in organ-specificity: target organ expression is dominated by long-lived endothelial cells, while off-target liver delivery and expression are in non-endothelial cells with shorter half-lives. Collectively, these studies demonstrate that targeted DNA-LNPs achieve high levels of organ- and cell-type-specific transgene expression and thus provide a therapeutic platform for dozens of endothelial-centric diseases.

  PublisherDOI

• Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis

  JCI Insight · 2025-07-01 · 7 citations

  articleOpen access

  Alveolar epithelial type II (AT2) cell dysfunction is implicated in the pathogenesis of familial and sporadic idiopathic pulmonary fibrosis (IPF). We previously demonstrated that expression of an AT2 cell-exclusive disease-associated protein isoform (SP-CI73T) in murine and patient-specific induced pluripotent stem cell-derived (iPSC-derived) AT2 cells leads to a block in late macroautophagy and promotes time-dependent mitochondrial impairments; however, how a metabolically dysfunctional AT2 cell results in fibrosis remains elusive. Here, using murine and human iPSC-derived AT2 cell models expressing SP-CI73T, we characterize the molecular mechanisms governing alterations in AT2 cell metabolism that lead to increased glycolysis, decreased mitochondrial biogenesis, disrupted fatty acid oxidation, accumulation of impaired mitochondria, and diminished AT2 cell progenitor capacity manifesting as reduced AT2 cell self-renewal and accumulation of transitional epithelial cells. We identify deficient AMPK signaling as a critical component of AT2 cell dysfunction and demonstrate that targeting this druggable signaling hub can rescue the aberrant AT2 cell metabolic phenotype and mitigate lung fibrosis in vivo.

  PublisherOA PDFDOI

• Stc1-expressing myofibroblasts are a developmentally distinct lineage cleared through intrinsic apoptosis in the neonatal lung

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-15

  preprintOpen access

  ABSTRACT Lung myofibroblasts are necessary for early postnatal alveolar growth and develop again during pathological fibrosis. Determining the unique contributions of multiple myofibroblast lineages to development and disease is hampered by a lack of genetic tools to distinguish between them. In this study, we generated a Stc1 CreERT2 mouse line that faithfully labels the developmentally transient secondary crest myofibroblasts (SCMF) and distinguishes SCMFs from alveolar duct myofibroblasts (DMF) and smooth muscle. SCMF populations expand by clonal proliferation of Stc1 -expressing progenitors and contract by apoptosis. We deleted the intrinsic apoptosis effectors Bax and Bak1 in the Stc1-lineage, which prevented SCMF clearance during alveologenesis. Single-cell RNA-seq revealed that residual Stc1-lineage cells lacking Bax and Bak1 lose myofibroblast identity but express a combination of SCMF and DMF marker genes. Embryonic lineage tracing identified that SCMFs and DMFs have distinct progenitor populations with unique niches, and genetic activation of developmentally important signaling pathways could not interconvert these lineages. These findings establish Stc1-lineage SCMFs as a discrete population, developmentally divergent from DMFs, and define their life cycle in isolation from other myofibroblast lineages.

  PublisherOA PDFDOI

• REGULATORY T CELLS PROTECT AGAINST ABERRANT REMODELING IN A MOUSE MODEL OF PULMONARY FIBROSIS

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-05

  preprintOpen access

  Regulatory T (Treg) cells are well recognized for their role in immune regulation; however, their role in tissue regeneration is not fully understood. This study demonstrates such a role of Tregs in a published preclinical murine model of spontaneous pulmonary fibrosis (PF) expressing a human PF related mutation in the Surfactant Protein-C (SP-C) gene (SFTPCI73T). Genetic crosses of SP-CI73T mice with Foxp3GFP and Foxp3DTR lines were utilized to study Treg behavior during PF development. We found that FoxP3+Tregs accumulate during the transition from inflammation to fibrogenesis, peaking at 21-28 days after mutant SftpcI73T induction localizing to both perivascular and distal fibrotic lung regions. Diphtheria toxin mediated ablation of Tregs at 17 days worsened fibrosis and increased levels of TGFβ and inflammatory cytokines. Tregs expressed Th2 markers (Gata3+) and elaborated factors including amphiregulin (Areg) and Osteopontin (Spp1). Reductionist experiments showed that lung Tregs enhanced organoid formation when co-cultured with alveolar epithelial cells and adventitial fibroblasts, an effect size mimicked using Areg and Spp1 in combination. Our findings demonstrate that immune-mesenchymal-epithelial signaling crosstalk is present in the distal lung wherein Tregs play a protective role by limiting fibrosis and promoting tissue repair, highlighting their broader function beyond immune modulation in lung injury.

  PublisherOA PDFDOI

• Regulatory T cells protect against aberrant remodeling in a mouse model of pulmonary fibrosis

  Mucosal Immunology · 2025-12-27

  article
  PublisherDOI

• Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape

  Nature Nanotechnology · 2025-08-11 · 42 citations

  articleOpen access
  PublisherOA PDFDOI

• Epithelial Deletion of Perk Reduces Lung Injury and Fibrosis in Multiple in Vivo Models of Epithelial Dysfunction and Lung Injury

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  articleSenior author

  Abstract Rationale: Activation of alveolar epithelial type 2 cell (AEC2) unfolded protein response (UPR) signaling is implicated in the epithelial response to acute lung injury and chronic pulmonary fibrosis. Among the vital AEC2 functions to maintain lung homeostasis is the production of pulmonary surfactant to reduce alveolar surface tension. Pulmonary fibrosis-associated mutations in the BRICHOS domain of Surfactant Protein C (SP-C) generate misfolded SP-C in AEC2s, leading to UPR activation and mechanistically tying AEC2 UPR to fibrosis. The PERK arm of the UPR is responsible for maintaining proteostatsis during cellular stress. We hypothesize that modulating PERK in AEC2s will maintain their function during intrinsic and extrinsic cell stress and subsequently protect the lung from injury and fibrosis. Methods: In our study, we exploited constitutive (Shh-Cre) and inducible (Sftpc-ERT2-Cre) genetic models of PERK knockout in conjunction with two lung injury and fibrosis models: the bleomycin model of extrinsic cell stress and our SP-C BRICHOS mutation model of intrinsic cell stress. Our in vivo experiments assessed AEC2 phenotype by gene expression and protein elaboration and lung phenotypes by histological analysis, lung injury assessments, and lung physiology changes. We coupled these in vivo experiments with ex vivo organoid assays to test the impact of PERK on AEC2 progenitor cell function. Results: Constitutive deletion of PERK in the lung epithelium resulted in protection from lung fibrosis in the bleomycin model, as suggested by histology, lung gene expression for fibrotic marker genes (Col1a1; Col3a1; Ctgf) BALF collagen content, and lung mechanics. We hypothesized that this protection may be from improved AEC2 progenitor cell function. We discovered through ex-vivo AEC2 alveolosphere culture that PERK knockout AEC2s have increased colony-forming efficiency (CFE) compared to wild-type AEC2s. In the SP-C BRICHOS model of AEC2 intrinsic cell stress and UPR, we found that PERK knockout also decreased lung injury markers. AEC2 gene expression analysis demonstrated maintenance of AEC2 identity with decreased transitional epithelial cell marker gene expression despite mutant SP-C protein. Conclusion: Our study indicates a critical role of PERK in lung epithelial cells during lung injury and fibrosis. PERK knock-out animals showed improved lung functions, enhanced ACE2 progenitor cell function, and maintenance of the ACE2 cell identity. While additional studies to identify how PERK signaling regulates these vital AEC2 functions are ongoing, our findings highlight a therapeutic role of this pathway in AEC2-driven lung disease.

  PublisherDOI

• Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids

  Nature Biotechnology · 2025-02-05 · 51 citations

  articleOpen access

  The value of lipid nanoparticles (LNPs) for delivery of messenger RNA (mRNA) was demonstrated by the coronavirus disease 2019 (COVID-19) mRNA vaccines, but the ability to use LNPs to deliver plasmid DNA (pDNA) would provide additional advantages, such as longer-term expression and availability of promoter sequences. However, pDNA-LNPs face substantial challenges, such as toxicity and low delivery efficiency. Here we show that pDNA-LNPs induce acute inflammation in naive mice that is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we loaded endogenous lipids that inhibit STING into pDNA-LNPs. Loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorated serious inflammatory responses in vivo, enabling safer, prolonged transgene expression-11.5 times greater than that of mRNA-LNPs at day 32. Additionally, we performed a small LNP formulation screen to iteratively optimize transgene expression and increase expression 50-fold in vitro. pDNA-LNPs loaded with NOA and other bioactive molecules should advance genetic medicine by enabling longer-term and promoter-controlled transgene expression.

  PublisherOA PDFDOI

• Animal and Translational Models for Precision Medicine in ILD

  Respiratory medicine · 2025-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• Characterizing the antifibrotic activity of bexotegrast on pathologic cell populations in multiple ILD subtypes

  2025-09-27

  article

  Bexotegrast, a dual inhibitor of TGF-β-activating integrins α_Vβ₆ and α_Vβ₁ currently in late-stage clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), was previously shown to reduce profibrotic gene expression in pathologic cell populations of precision-cut lung slices (PCLS) generated from IPF patient lung explants. Here we used single-nuclei RNA sequencing (snRNA-seq) to evaluate the antifibrotic activity of bexotegrast in non-IPF interstitial lung disease (ILD) patient explants. PCLS were generated from lung explants obtained at transplant from patients with non-IPF fibrosing ILDs (e.g. rheumatoid arthritis-associated-ILD and hypersensitivity pneumonitis). After 7 days of treatment with bexotegrast or vehicle, nuclei were isolated and sequenced. Differential gene expression analysis (│log2FC│ > 0.25, FDR < 0.05) was performed on cell populations annotated based on published markers. snRNA-seq analysis identified distinct cell populations in PCLS, including integrin β₆ (ITGB6)-expressing epithelial cells (e.g. ATI and ATII) and multiple fibroblast populations (e.g. profibrotic, myofibroblast and adventitial). Bexotegrast significantly reduced the expression of matrisome components across fibroblast subtypes, including collagens, ECM glycoproteins, and ECM regulators (e.g. COL1A1, SPARC, SULF1). In ATI cells, bexotegrast also significantly reduced expression of genes related to TGF-β signaling (e.g. ITGB6 and SMAD7), actin binding and focal adhesions. These findings demonstrate the antifibrotic activity of bexotegrast in fibrotic human lung tissue and support further investigation of bexotegrast in ILD-associated progressive pulmonary fibrosis.

  PublisherDOI

Recent grants

• Understanding how alveolar epithelial cell stress drives aberrant repair in interstitial lung disease

  NIH · $840k · 2020–2025

Frequent coauthors

• Michael F. Beers

  University of Pennsylvania

  50 shared

• Yaniv Tomer

  University of Pennsylvania

  34 shared

• Bruce M. Becker

  Providence College

  31 shared

• Edward E. Morrisey

  University of Pennsylvania

  31 shared

• Kenneth H. Mayer

  Fenway Health

  31 shared

• Roland C. Merchant

  31 shared

• Jackson Helmer

  New York University Press

  25 shared

• Eitan Melamed

  Icahn School of Medicine at Mount Sinai

  25 shared