Positions
- Associate Professor
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Medicine
Immunology, Allergy & Rheumatology
Baylor College of Medicine
Houston, TX, US
- Graduate Faculty Member
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Immunology & Microbiology
Baylor College of Medicine
- Graduate Faculty Member
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Development, Disease Models & Therapeutics
Baylor College of Medicine
- Core Faculty
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Center for Translational Research on Inflammatory Diseases (CTRID)
Michael E. DeBakey VA Medical Center
Baylor College of Medicine
Houston, Texas, United States
Addresses
- Main Office (Office)
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Baylor College of Medicine
Room: N903.02 Alkek
Houston, TX, 77030
United States
Phone: (713) 798-2664
Education
- PhD from University of Texas Southwestern Medical Center
- Houston, Texas, United States
- Genetics, Development, Programmed Cell Death
- Postdoctoral Fellowship at Wellcome Trust Sanger Institute
- Cambridge, United Kingdom
- microRNAs, Immunology, Stem cells, Genomics
Professional Interests
- Epithelial stem cell dysfunction in COPD and interstitial lung disease
- Chromatin remodeling and lncRNA-mediated gene regulation in lung disease
- MicroRNA-driven epigenetic regulation of epithelial stem cell fate
- Lung repair, regeneration, and fibrosis
Professional Statement
Our laboratory studies how microRNA-driven epigenetic programs control epithelial stem cell fate in lung injury and chronic disease. We focus on how disruption of these pathways leads to aberrant chromatin states, impaired regeneration, and fibrosis in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).
We have identified the let-7 microRNA family as a central regulator of epithelial stem cell identity and chromatin state in the lung.
In a recent study, we showed that loss of let-7 induces a maladaptive, epigenetic program in alveolar type II (AT2) progenitor cells. This state promotes aberrant stem cell activation, expansion of KRT8+ intermediates, impaired differentiation, and susceptibility to fibrosis. Mechanistically, let-7 regulates key epigenetic pathways involving EZH2, linking microRNA fibrotic signaling to reprogramming AT2 cells via histone H3 lysine 27 trymethylation and acetylation.
We integrate genetically engineered mouse models, 3D AT2 organoid systems, and advanced genomic and epigenomic approaches (including scRNA-seq, CUT&RUN, and AGO2-eCLIP) with human studies using RNA-seq datasets, primary AT2 cells 3D organoid cultures from patients with idiopathic pulmonary fibrosis, and precision-cut lung slices to define how let-7–dependent epigenetic programs regulate epithelial stem cell behavior across experimental and human disease contexts.
Our work defines how microRNAs regulate chromatin state and stem cell behavior, providing a framework for developing new therapies for chronic lung disease.
We have identified the let-7 microRNA family as a central regulator of epithelial stem cell identity and chromatin state in the lung.
In a recent study, we showed that loss of let-7 induces a maladaptive, epigenetic program in alveolar type II (AT2) progenitor cells. This state promotes aberrant stem cell activation, expansion of KRT8+ intermediates, impaired differentiation, and susceptibility to fibrosis. Mechanistically, let-7 regulates key epigenetic pathways involving EZH2, linking microRNA fibrotic signaling to reprogramming AT2 cells via histone H3 lysine 27 trymethylation and acetylation.
We integrate genetically engineered mouse models, 3D AT2 organoid systems, and advanced genomic and epigenomic approaches (including scRNA-seq, CUT&RUN, and AGO2-eCLIP) with human studies using RNA-seq datasets, primary AT2 cells 3D organoid cultures from patients with idiopathic pulmonary fibrosis, and precision-cut lung slices to define how let-7–dependent epigenetic programs regulate epithelial stem cell behavior across experimental and human disease contexts.
Our work defines how microRNAs regulate chromatin state and stem cell behavior, providing a framework for developing new therapies for chronic lung disease.
Websites
Selected Publications
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Nam JW, Rissland OS, Koppstein D, Abreu-Goodger C, Jan CH, Agarwal V, Yildirim MA, Rodriguez A, Bartel DP. " Global analyses of the effect of different cellular contexts on microRNA targeting " Mol Cell. 2014 Mar 20;
Pubmed PMID: 24631284. -
Erice PA , Huang X , Seasock MJ , Robertson MJ , Tung H-Y, Perez-Negron MA, Lotlikar SL, Corry DB, Kheradmand F, Rodriguez A. " Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORgammat " Elife. 2024 ;
Pubmed PMID: 38722677. -
Seasock MJ, Shafiquzzaman M, Ruiz-Echartea M, Kanchi R, Tran B, Simon L, Meyer M, Erice P, Lotlikar S, Wenlock S, Ochsner S, Enright A, Carisey A, Romero F, Rosas I, King K, McKenna N, Coarfa C, Rodriguez A. " Let-7 restrains an epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic cell intermediates and pulmonary fibrosis " Nature Communications. 2025 May ;
Pubmed PMID: 38826218. -
Gurha P, Abreu-Goodger C, Wang T, Ramirez MO, Drumond AL, van Dongen S, Chen Y, Bartonicek N, Enright AJ, Lee B, Kelm RJ, Reddy AK, Taffet GE, Bradley A, Wehrens XH, Entman ML, Rodriguez A. " Targeted deletion of microRNA-22 promotes stress-induced cardiac dilation and contractile dysfunction " Circulation. 2012 Jun 5;
Pubmed PMID: 22570371.
Funding
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Mechanism and Function of let-7, a Novel Modulator of Emphysema
#1R0-1HL140398 - Grant funding from NIH (NHLBI)
- PI
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Delineating the Role and let-7 microRNA on Lung AT2 Cell Homeostasis, Alveolar Regeneration, and Interstitial Lung Disease
#1R01-HL167814 - Grant funding from NIH (NHLBI)
- PI
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Lung stem cell role of the let-7 family
- Nancy Chang Research Excellence Award
- PI
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