Jarod Zepp, PhD, is interested in delineating the lineage relationships of fibroblast subsets and their contribution to lung function or repair after injury. Depending on the organ and tissue type, under steady-state conditions, some cells can proliferate and differentiate into other specialized cell types. In barrier organs, such as the skin, gut and lung, cells exposed to the external environment undergo regular cycles of proliferation and differentiation to maintain a functional barrier. In the lung, the epithelial layer is in direct contact with inhaled air. Research efforts over the last two decades have carefully mapped out the replicative nature of sub-types of epithelial cells and pathways that are activated to promote differentiation. Recent studies have shifted attention to other cell types in the lung, namely endothelial cells and fibroblasts/smooth muscle.
Fibroblasts and smooth muscle surround the epithelium and vasculature in the lung. Using a combination of mouse genetic lineage tracing, fluorescence imaging and single-cell RNA sequencing, functionally distinct subsets of fibroblasts are being characterized. These fibroblasts have unique capacities to proliferate, differentiate and secrete growth factors that support epithelial or endothelial cell growth. We are focused on identifying signaling pathways and transcription factors that control the differentiation of fibroblasts in a variety of in vivo models and then translating these findings to better understand human pulmonary disease with fibroblast involvement.
PhD - Case Western Reserve University (Molecular Medicine), Cleveland, OH
Assistant Professor, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Assistant Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
Zepp et al, “The genomic, epigenomic, and biophysical cues controlling the emergence of the lung alveolus.” Science, online March 12, 2021. DOI: 10.1126/science.abc3172.
Chao CM, Bellusci S, Zepp JA. P16INK4a and the Alveolar Niche Take Center Stage in Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2020 Jul 15. PMID:32668168
Zepp JA, Alvira CM. Nanoparticle delivery of Angiogenic Gene Therapy: Save the Vessels, Save the Lung! Am J Respir Crit Care Med. 2020 Apr 27. PMID:32338996
Niethamer TK, Stabler CT, Leach JP, Zepp JA, Morley MP, Babu A, Zhou S, Morrisey EE. Defining the Role of Pulmonary Endothelial Cell Heterogeneity in the Response to Acute Lung Injury. Elife. 2020 Feb 24;9:e53072. PMID: 32091393
Liberti DC, Zepp JA, Bartoni CA, Liberti KH, Zhou S, Liu M, Morley MP, Morrisey EE. Dnmt1 is required for proximal-distal patterning of the lung endoderm and for restraining alveolar type 2 cell fate. Dev Biol. 2019 Jun 23. PMID:31242446.
Zepp JA and Morrisey EE. Cellular crosstalk in the development and regeneration of the respiratory system. Nat Rev Mol Cell Biol. 2019 Jun 19. PMID:31217577.
Frank DB, Penkala IJ, Zepp JA, Sivakumar A, Linares-Saldana R, Zacharias WJ, Stolz KG, Pankin J, Lu M, Wang Q, Babu A, Li L, Zhou S, Morley MP, Jain R, Morrisey EE. Early lineage specification defines alveolar epithelial ontogeny in the murine lung. Proc Natl Acad Sci U S A. 2019 Feb 19. PMID:30782824
Bulek K, Chen X, Parron V, Sundaram A, Herjan T, Ouyang S, Liu C, Majors A, Zepp J, Gao J, Dongre A, Bodaszewska-Lubas M, Echard A, Aronica M, Carman J, Garantziotis S, Sheppard D, Li X. IL-17A Recruits Rab35 to IL-17R to Mediate PKCα-Dependent Stress Fiber Formation and Airway Smooth Muscle Contractility. J Immunol. 2019 Mar 1;202(5):1540-1548. PMID: 306833702.
Zacharias WJ, Frank DB, Zepp JA, Morley MP, Alkhaleel F, Kong J, Zhou S, Cantu E, Morrisey EE. 2018. Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Nature. Feb 28. PMID:29489752.
Zepp JA, Frank DB, Zacharias WJ, Cavanaugh C, Morley MM, Morrisey EE. Distinct mesenchymal lineages and niches promote epithelial self-renewal and myofibrogenesis in the lung. Cell. Sep 7;170(6):1134-1148. PMID:28886382.
Frank DB, Peng T, Zepp JA, Snitow M, Vincent T, Penkala IJ, Herriges MJ, Morley MP, Zhou S, Lu MM, Morrisey EE. Emergence of a wave of Wnt signaling that regulates lung alveologenesis through controlling epithelial self-renewal and differentiation. Cell Reports. Nov 22;17(9):2312-2325. PMID:27880906.
2013, Outstanding Scholar Award, First Prize, International Society of Interferon and Cytokine Research