Positions
- Assistant 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
- microRNA regulation of COPD and IPF
- lung repair and regeneration
- inflammation mediated lung injury
- let-7 Stem Cell Circuits in Lung Disease
Professional Statement
The lab focuses on microRNA-mediated posttranscriptional mechanisms in lung physiology and tissue repair following injury. We are particularly focused on how hijacking of microRNA pathways contribute to epithelial stem cell dysfunction in pathophysiology of chronic obstructive pulmonary disease (COPD) and Interstitial Lung Disease (ILD). COPD and ILD are serious disorders associated with irreversible damage to the lung and chronic inflammation. microRNA biology offers an innovative opportunity for interventions in these challenging diseases. Our research found that miRNA post-transcriptional signals and mechanisms are pivotal in lung stem cell dynamics, immune cell inflammation in COPD and ILD.We and others have shown reduced expression of the let-7 miRNA family in human tissues and pre-clinical models of COPD and ILD. The let-7 miRNA family is an ancient and critically important gene associated with diseases such as cancer and organ fibrosis.
In the immune system, we recently demonstrated that let-7 directly controls RORγt expression which leads to excessive formation of IL17+ CD8+ T cells (Tc17), which sensitizes lungs of mice to injury and tissue destruction in COPD.
Within pulmonary alveolar type II (AT2) progenitor stem cells, we found that let-7 governs a maladaptive “cancer-like” molecular epigenomic program associated with an enhanced stem cell activation state which promotes lung injury, immune cell inflammation, fibrosis, and ILD.
Our lab utilizes unique animal models together with 3D organoid lung epithelial stem cell cultures to identify key regulatory mechanisms of microRNAs. We further make use of innovative techniques such as chimeric AGO2-eCLIP, scRNA-seq, and CUT&RUN.
Our work offers novel therapeutic strategies that can be used to treat severe lung diseases.
Websites
Selected Publications
- 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 oncogenic epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic cell intermediates and pulmonary fibrosis." BioRxiv. 2024 May; Pubmed PMID: 38826218
- Morales-Mantilla DE; Xinyan Huang; Erice P; Porter P; Yun ZHANG; Mary Figueroa; Chandra J; Katherine King; Kheradmand F; Antony Rodriguez "Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System." JoVE. 2022 Oct; Pubmed PMID: 33165327
- 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
- Gurha P, Wang T, Larimore AH, Sassi Y, Abreu-Goodger C, Ramirez MO, Reddy AK, Engelhardt S, Taffet GE, Wehrens XH, Entman ML, Rodriguez A "microRNA-22 promotes heart failure through coordinate suppression of PPAR/ERR-nuclear hormone receptor transcription." PLoS One. 2013; Pubmed PMID: 24086656
- Lu W, You R, Yuan X, Yang T, Samuel EL, Marcano DC, Sikkema WK, Tour JM, Rodriguez A, Kheradmand F, Corry DB "The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema." Nat Immunol. 2015 Nov; Pubmed PMID: 26437241
Funding
- Mechanism and Function of let-7, a Novel Modulator of Emphysema - #1R0-1HL140398 (09/01/2018 - 08/31/2023) Grant funding from NIH (NHLBI)
- PI
- Delineating the Role and let-7 microRNA on Lung AT2 Cell Homeostasis, Alveolar Regeneration, and Interstitial Lung Disease - #1R01-HL167814 (04/03/2023 - 03/31/2028) Grant funding from NIH (NHLBI)
- PI
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