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UF Health University of Florida
Division of Pulmonary, Critical Care & Sleep Medicine Department of Medicine in the College of Medicine
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Khodayari Lab

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Dr. Khodayari’s lab focuses on understanding the mechanisms of tissue injury mediated by Alpha-1 Antitrypsin Deficiency, a genetic disorder that impacts both pulmonary and hepatic health. We investigate how the protease-antiprotease imbalance in Alpha-1 Antitrypsin Deficiency contributes to chronic inflammation, impaired tissue repair, and fibrosis in multiple organs. By studying the cellular and molecular pathways underlying these processes, we aim to identify novel therapeutic strategies to mitigate tissue damage and improve outcomes for individuals affected by Alpha-1 Antitrypsin Deficiency.

Personal Statement

Nazli Khodayari
Nazli Khodayari, PhD

As a dedicated scientist, my research focuses on unraveling the complex mechanisms underlying Alpha-1 Antitrypsin Deficiency, with a particular emphasis on its impact on tissue injury and repair. My work spans critical areas, including the intricate lung-liver crosstalk that mediates systemic inflammation and tissue damage, the role of extracellular vesicles in intercellular communication and disease progression, and the processes driving liver fibrosis and inflammation in the context of Alpha-1 Antitrypsin Deficiency.

Through my research, I aim to elucidate how Alpha-1 Antitrypsin Deficiency -associated protease-antiprotease imbalances influence cellular signaling and immune responses, contributing to chronic inflammation and organ dysfunction. By exploring the role of extracellular vesicles as mediators of systemic effects and investigating the molecular pathways linking lung and liver pathology, I hope to uncover novel therapeutic targets to mitigate the dual-organ damage observed in Alpha-1 Antitrypsin Deficiency. My passion for translational science drives me to connect fundamental discoveries with potential clinical applications, ultimately striving to improve the quality of life for patients living with Alpha-1 Antitrypsin Deficiency and related conditions.

Lab Faculty and Staff

Laboratory Manager

Regina Oshins

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Publication Highlights

  • 2024 Essential role of Hepcidin in host resistance to disseminated candidiasis. bioRxiv : the preprint server for biology. [DOI] 10.1101/2024.10.29.620511. [PMID] 39553949.
  • 2024 Extracellular Vesicle-Associated Neutrophil Elastase Activates Hepatic Stellate Cells and Promotes Liver Fibrogenesis via ERK1/2 Pathway. bioRxiv : the preprint server for biology. [DOI] 10.1101/2024.08.20.608832. [PMID] 39229038.
  • 2024 Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease. Journal of Clinical and Translational Hepatology. 000(000):000-000 [DOI] 10.14218/jcth.2024.00201.
  • 2024 Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease. Journal of Clinical and Translational Hepatology. 000(000):000-000 [DOI] 10.14218/jcth.2024.00253.
  • 2024 Sirtuin3 promotes the degradation of hepatic Z alpha-1 antitrypsin through lipophagy. Hepatology communications. 8(2) [DOI] 10.1097/HC9.0000000000000370. [PMID] 38285890.
  • 2023 Augmentation Therapy Modulates Systemic Inflammation in Individuals with Alpha-1 Antitrypsin Deficiency and Chronic Obstructive Pulmonary Disease. Chronic obstructive pulmonary diseases (Miami, Fla.). 10(3):308-316 [DOI] 10.15326/jcopdf.2023.0407. [PMID] 37363834.
  • 2023 Correction to: Cigarette smoke exposed airway epithelial cells-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency. Respiratory research. 24(1) [DOI] 10.1186/s12931-023-02571-7. [PMID] 37925417.
  • 2023 Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function. Respiratory research. 24(1) [DOI] 10.1186/s12931-023-02343-3. [PMID] 36732772.
  • 2023 Using ChatGPT to predict the future of personalized medicine. The pharmacogenomics journal. 23(6):178-184 [DOI] 10.1038/s41397-023-00316-9. [PMID] 37726551.
  • 2022 BRCA1 mediates protein homeostasis through the ubiquitination of PERK and IRE1. iScience. 25(12) [DOI] 10.1016/j.isci.2022.105626. [PMID] 36471805.
  • 2022 Characterization of hepatic inflammatory changes in a C57BL/6J mouse model of alpha1-antitrypsin deficiency. American Journal of Physiology-Gastrointestinal and Liver Physiology. 323(6):G594-G608 [DOI] 10.1152/ajpgi.00207.2022.
  • 2022 Cigarette smoke exposed airway epithelial cell-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency. Respiratory research. 23(1) [DOI] 10.1186/s12931-022-02161-z. [PMID] 36068572.
  • 2022 Correlation of alpha-1 antitrypsin levels and exosome associated neutrophil elastase endothelial injury in subjects with SARS-CoV2 infection. PLOS ONE. 17(9) [DOI] 10.1371/journal.pone.0274427. [PMID] 36084115.
  • 2022 Reply. Hepatology Communications. 6(12):3599-3599 [DOI] 10.1002/hep4.2084. [PMID] 36017787.
  • 2022 The unfolded protein response to PI*Z alpha‐1 antitrypsin in human hepatocellular and murine models. Hepatology Communications. 6(9):2354-2367 [DOI] 10.1002/hep4.1997. [PMID] 35621045.
  • 2021 The Mechanism of Mitochondrial Injury in Alpha-1 Antitrypsin Deficiency Mediated Liver Disease. International journal of molecular sciences. 22(24) [DOI] 10.3390/ijms222413255. [PMID] 34948056.
  • 2020 Alpha-1 antitrypsin deficient individuals have circulating extracellular vesicles with profibrogenic cargo. Cell Communication and Signaling. 18(1) [DOI] 10.1186/s12964-020-00648-0. [PMID] 32887613.
  • 2020 Gut microbiota: a perspective of precision medicine in endocrine disorders. Journal of diabetes and metabolic disorders. 19(2):1827-1834 [DOI] 10.1007/s40200-020-00593-2. [PMID] 33520863.
  • 2020 Neutrophil elastase promotes macrophage cell adhesion and cytokine production through the integrin-Src kinases pathway. Scientific reports. 10(1) [DOI] 10.1038/s41598-020-72667-3. [PMID] 32981934.
  • 2019 Modulation of calreticulin expression reveals a novel exosome-mediated mechanism of Z variant α1-antitrypsin disposal. Journal of Biological Chemistry. 294(16):6240-6252 [DOI] 10.1074/jbc.ra118.006142.
  • 2019 Modulation of calreticulin expression reveals a novel mechanism of Z variant alpha-1 Antitrypsin disposal. Molecular Biology of the Cell. 28
  • 2017 Alpha-1 Antitrypsin-Deficient Macrophages Have Increased Matriptase-Mediated Proteolytic Activity. American journal of respiratory cell and molecular biology. 57(2):238-247 [DOI] 10.1165/rcmb.2016-0366OC. [PMID] 28362108.
  • 2017 Erdj3 Has an Essential Role for Z Variant Alpha‐1‐Antitrypsin Degradation. Journal of Cellular Biochemistry. 118(10):3090-3101 [DOI] 10.1002/jcb.26069. [PMID] 28419579.
  • 2017 SVIP regulates Z variant alpha-1 antitrypsin retro-translocation by inhibiting ubiquitin ligase gp78. PloS one. 12(3) [DOI] 10.1371/journal.pone.0172983. [PMID] 28301499.
  • 2016 MicroRNA-302b targets Mcl-1 and inhibits cell proliferation and induces apoptosis in malignant pleural mesothelioma cells. American journal of cancer research. 6(9):1996-2009 [PMID] 27725905.
  • 2014 Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling. American journal of physiology. Cell physiology. 306(12):C1154-66 [DOI] 10.1152/ajpcell.00415.2012. [PMID] 24717580.
  • 2012 Advances in malignant pleural mesothelioma therapy: targeting EphA2 a novel approach. American journal of cancer research. 2(2):222-34 [PMID] 22432060.
  • 2012 Fluticasone propionate and Salmeterol combination induces SOCS-3 expression in airway epithelial cells. International immunopharmacology. 12(1):217-25 [DOI] 10.1016/j.intimp.2011.11.014. [PMID] 22155101.
  • 2011 EphrinA1 inhibits malignant mesothelioma tumor growth via let-7 microRNA-mediated repression of the RAS oncogene. Cancer gene therapy. 18(11):806-16 [DOI] 10.1038/cgt.2011.50. [PMID] 21869823.