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Shervin Takyar, MD, PhD

Associate Professor

Contact Information

Shervin Takyar, MD, PhD

Patient Care Locations

Mailing Address

  • PO Box 208057

    300 Cedar Street

    New Haven, CT, 06520-8057

    United States

Appointments

Biography

I did my PhD in microbiology and molecular biology in The University of Queensland, Australia. During my PhD I worked and published on a variety of projects including developing a new lentiviral vector based on JDV (Jembrana Disease Virus), translational regulation in HCV by small RNA-binding molecules and the viral core protein, and RNA-protein interactions in positive strand RNA viruses. During this time I was also involved in cloning the Australian isolate of HCV with Dr Eric Gowans. My findings in these projects were published in a variety of journal including PNAS, Hepatology, and Journal of Molecular Biology.My next stop was a postdoctoral fellowship with Prof. Harry Noller at the RNA Center in UCSC where I delved deeper into the RNA world and studied the helicase activity of the ribosome during translation. Our work was well received and published in Cell.

I started my Internal Medicine residency at the State University of New York (SUNY) at Buffalo in 2003. During the last year of my residency I took part in a research project led by Dr Sands on the role of TIMP-1 in reactive airway disease. Our work was published in Clinical Immunology. I was then recruited to the Pulmonary Critical Care Fellowship at Yale in 2007, and worked with Dr J Elias to set up a platform for analyzing the role of microRNAs in the lung disease using the transgenic models that have been developed in his lab. I started this work on an inducible, lung-specific, VEGF transgenic model and within the first year of the project found a microRNA that was regulated by VEGF and mediated the effects of this cytokine in the lung. Based on these findings we filed a patent on the diagnostic and therapeutic use of miR-1 in lung disease. I received a K99/R00 award in the third year of my clinical fellowship for my work on this project. I was directly recruited as a tenure-track Assistant Professor in the Yale Pulmonary, Critical Care and Sleep Medicine Section at the end of my fellowship.

I started the R00 phase of my grant in 2014. I established my lab in the Pulmonary and Critical Care Section at Yale and was given a secondary appointment in the Department of Molecular Biophysics and Biochemistry. Focusing on the role of endothelial gene regulation in injury, I collaborated with Dr. P Lee a Yale to show that VEGF is a part of a TLR4-driven protective pathway in the lung endothelium. We showed the significance of this pathway in a variety of endothelial-specific models and published the results in FASEB journal in 2015.

In the next phase, we developed vector-based and transgenic models for endothelial-cell-specific miRNA expression and showed that miR-1 effects on inflammation and remodeling are due to its specific role in the lung endothelium. I started a collaboration with Yale Thoracic Interventional and Yale Thoracic Oncology programs on lung cancer and showed that miR-1 is a predictor of lung cancer survival and is regulated in tumor endothelial cells. As a part of this work we also set up several lung cancer models in the lab, including the KRAS mutant/P53 knockout mouse model I was awarded the American Lung Association Cancer Discovery Award in 2013, presented my findings at ATS in 2014, 2015, and 2016 and published a manuscript describing these results in the American Journal of Respiratory and Critical Care Medicine (AJRCCM) in 2017.

I have followed my molecular studies on miR-1 in several directions. Our studies on the role of miR-1 in tumor endothelium has led to the identification of a novel non-templated addition (NTA) enzymatic pathway. We also found that PI3 kinase/Akt pathway controls miR-1 levels in the endothelium. We presented these findings at the Keystone symposium on “MicroRNAs and Noncoding RNAs,” at the “Lung Development, Injury and Repair” Gordon Research Conference in 2016, at the ATS in 2016, 2017, and 2018. We have continued our studies on the role of miR-1 in the tumor stroma and found that it is regulated in the cancerization field. The preliminary results from these studies were presented at ATS 2018 and 2019.

Following the specific role of miR-1 in the endothelium, we used our vascular specific miRNA expression models to probe the specific roles of endothelial miR-1 in airway inflammation. We also developed an Argonaute 2 cross-linking and immunoprecipitation (Ago-CLIP) method to identify novel miR-1 targets through miRISC analysis. Using these two methods we showed that isolated overexpression of miR-1 in the lung endothelium significantly decreases the severity of airway inflammation and mediates this mechanism through downregulation of eosinophil trafficking genes. Also, through our collaboration with Yale Center for Asthma and Airway Disease (YCAAD), and the Ear Nose Throat Department at Yale, we showed the significance of this miRNA-regulated gene network in human asthma and chronic rhinosinusitis. These findings were published in Journal of Allergy and Clinical Immunology (JACI) in 2020.

Since starting my tenure track position in 2010 I have been awarded the AAP (American Association of Physicians) Junior Investigator Award, ALA Lung Cancer Discovery Award, NIH/NIAID R56 award , ATS R to R award, and a DOD Lung Cancer Idea Development award. We have published our work on asthma and Th2 inflammation in Journal of Experimental Medicine, and Journal of Allergy and Clinical Immunology, our work on non-small cell lung caner tumor endothelium and cancer progression in the American journal of Respiratory and Critical Care Medicine, and our work on the role of endothelium in lung injury in FASEB journal. I have recruited and worked with five postdoctoral fellows, four Associate Research Scientists, and four students over the last seven years. My research currently focuses on the role of vascular non-coding RNAs in cancer, lung injury and airway inflammation.

Education & Training

  • PhD
    University of Queensland (2002)
  • MD
    Iran University of Medical Sciences (1995)
  • Fellow
    Yale University School of Medicine
  • Resident
    State University of New York - Buffalo
  • Fellow
    University of California at San Cruz
  • PG1
    University of Queensland
  • Board Certification
    AB of Internal Medicine, Pulmonary Disease (2012)

Activities

  • A. Korde, F. Ahangari, M. Haslip, G.L. Chupp, J. Pober, A. Gonzalez, J.L. Gomez, S. Takyar. Endothelial Thrombopoietin Receptor Regulates The Severity Of Type 2 Inflammation By Controlling Plateleteosinophil
    Philadelphia, United States 2020
  • A. Korde, S. Anderson, M. Haslip, S. Takyar. Gram Negative Infection Accelerates Lung Endothelial Cell Death Through Regulation of MicroRNA-1/Angiopoietin-2 Pathway
    Dallas, United States 2019
  • B. Hu, A. Korde, L.E. Cohn, J.-H. Chu, S. Takyar. Poster: Human Lung MicroRNA-1 Is Regulated by IL-13 and Correlates with Tissue Eosinophilia in Airway Inflammation
    Dallas, United States 2019
  • A. Korde, A. Ramaswami, M.S. Godfrey, S. Anderson, S. Takyar. Poster Discussion: Cigarette Smoke Activates PI3 Kinase Pathway and Downregulates MicroRNA-1 in Non-Small Cell Lung Cancer (NSCLC)
    Dallas, United States 2019
  • Asthma is Associated with Benign Glandular Neoplasms in a Large-Scale Population-Based Cohort
    San Diego, United States 2018
  • 3’-RNA Adenylation Enzymes Control Allergic Inflammation Through Regulation of MicroRNA Degradation
    San Diego, United States 2018
  • Eosinophil Binding and Activation is Regulated Through the Coordinated Expression of miR-1 Endothelial Targets
    San Diego, United States 2018
  • A Herpesvirus Noncoding RNA Controls NSCLC Tumor Progression Through Selective Degradation of miR-27 in Immune Cells
    San Diego, United States 2018
  • RNA Modification Enzymes Control Non Small Cell Tumor Growth Through Regulation of the Angiogenic Response
    Washington, United States 2017
  • RNA Modification Enzymes Control Non Small Cell Tumor Growth Through Regulation of the Angiogenic Response
    Washington, United States 2017
  • Cell-specific MicroRNA-driven Pathway Controls the Recruitment of Eosinophils in Type 2 Inflammation
    Washington, United States 2017
  • Cell-specific MicroRNA-driven Pathway Controls the Recruitment of Eosinophils in Type 2 Inflammation
    Washington, United States 2017
  • MicroRNA-1 Levels Determine the Type of Inflammatory Remodeling in Chronic Rhinosinusitis
    Washington, United States 2017
  • From inflammation to cancer: trials and tribulations of an endothelial microRNA
    Denver, United States 2016
  • Non-Small Cell Lung Cancer (NSCLC) Tumor Progression is Inhibited in an Inducible Vascular-Specific MicroRNA-1 (miR-1) Transgenic Model
    San Francisco, United States 2016
  • VEGF Induces Lung Angiogenesis Through "Tailing and Trimming" of MicroRNAs and Production of 3'-Modified IsomiRs
    San Francisco, United States 2016
  • MiR-1 Expression in the Vicinity of Non-Small Cell Cancer Correlates with Patient Survival
    San Francisco, United States 2016
  • Lung Endothelial miR-1 Recruits Angiopoietin-2 to RNA Induced Silencing Complex (RISC) and Protects Lungs against Oxidant Injury through an Angiocrine Mechanism
    Andover, United States 2015
  • An Intrinsic Endothelial miR-1 Degradation Pathway Regulates Non-Small Cell Lung Cancer (NSCLC) Tumor Vascularity and Progression
    Keystone, United States 2015
  • Endothelial microRNA-1 Protects against Lung Hyperoxic Injury and Downregulates Ang2 Expression
    Denver, United States 2015
  • An intrinsic endothelial miR-1 pathway controls vascular activation in asthma and lung cancer
    Bethesda, United States 2014
  • An Endothelial microRNA Circuit Controls Vascular Activation in Asthma and Lung Cancer
    Rahway, United States 2014
  • An Endothelial-specific VEGF Receptor 2-miR-1-Mpl Circuit Controls the Severity of Lung Th2 Inflammation
    San Diego, United States 2014
  • Endothelial miR-1 is Downregulated in Lung Cancer Models and Controls the Progression of Lung Tumors through Inhibition of VEGF Signaling
    Philadelphia, United States 2013
  • TLR4 Protects the Lung Against Oxidant-induced Injury by Regulating the Endothelial Response to VEGF
    Philadelphia, United States 2013
  • MiR-1 Enters the RNA Induced Silencing Complex (RISC) in the Lung and Inhibits Th2 Inflammation
    Philadelphia, United States 2013
  • Mpl is Targeted by MiR-1 in the Lung Endothelial Cells and Regulates Th2 Inflammation by Controlling Adhesion Molecule Expression
    San Francisco, United States 2012
  • MiR-1 Inhibits adaptive Th2 Inflammation in the Lung via a VEGF/Mpl Axis
    Waltham, United States 2011
  • MicroRNA (miR)-1 Inhibits Adaptive Th2 Inflammation in the Lung via a VEGF/Myeloproliferative Leukemia Virus Oncogene (Mpl)-Dependent Mechanism
    Denver, United States 2011
  • Biology of Signaling in the Cardiovascular System
    Barnstable, United States 2011
  • MiR-1 inhibits Allergic Airway Inflammation by Targeting Mpl (Myeloproliferative Leukemia Virus Oncogene) in the Lung Endothelium
    Chicago, United States 2011
  • miR-1 Inhibits Adaptive Th2 Inflammation in the Lung via a VEGF/Myeloproliferative Leukemia Virus Oncogene (Mpl)-Dependent Mechanism
    Banff, Canada 2011
  • MiR-1 Regulates VEGF-induced Angiogenic Responses in the lung by Inhibiting the Myeloproliferative Leukemia Virus Oncogene (MPL)
    Seebruck, Germany 2010
  • MiR-1 Regulates VEGF-induced Angiogenic Responses in the lung by Inhibiting the Myeloproliferative Leukemia Virus Oncogene (MPL)
    New Orleans, United States 2010
  • MiR-1 is a Critical Regulator of VEGF-Induced Angiogenesis
    San Diego, United States 2009
  • Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Modulates Lung Hyperreactivity and Inflammation in a Murine Asthma Model
    Miami, United States 2006
  • Mechanism and Control of Posttranscriptional Gene Expression
    New York, United States 2005
  • mRNA helicase activity of the ribosome
    New York, United States 2005
  • A ribosomal helicase: unwinding mRNA during ribosomal translocation
    San Francisco, United States 2003
  • Cyanocobalamin-HCV IRES interaction: a molecular model for translational regulation
    Stanford, United States 2001
  • Cyanocobalamin can stall the ribosomal complexes on hepatitis C virus internal ribosomal entry site: a novel mechanism of translational control
    Sydney, Australia 2001
  • Modulation of HCV IRES-dependent translation by HCV capsid protein
    Sydney, Australia 2001
  • Exploring a natural role for cobalamins in hepatitis C virus replication
    Sydney, Australia 2001
  • Biochemical characterization of the cyanocobalamin-HCV IRES interaction: A novel mechanism of eukaryotic translational control
    Gold Coast, Australia 2000
  • Probing the structure-function relationship in HCV internal ribosomal entry site using RNA pseudoknot binding molecules
    Gold Coast, Australia 2000
  • Structure-function relationship in HCV internal ribosomal entry site
    Cairns, Australia 2000
  • Specific detection of negative strand hepatitis C virus RNA by RT-PCR on poly A purified RNA
    Sydney, Australia 2000
  • Testing cobalamin-analogous compounds on HCV IRES-dependent translation
    Sydney, Australia 2000
  • Potential involvement of polypyrimidine tract binding protein in mediating interactions between the 5’UTR and 3’UTR of HCV
    Sydney, Australia 2000
  • RNA pseudoknot-binding molecules modulate HCV IRES-dependent translation
    Sydney, Australia 2000
  • Inhibition of Translation initiation in HCV: Implications for a novel antiviral drug design
    Sydney, Australia 1999
  • The Role of 3’ U5 in a Novel Lentiviral Vector System
    Melbourne, Australia 1999
  • Cytogenetic and epidemiologic study on 1100 trisomic 21 patients
    Shiraz, Iran 1998

Honors & Recognition

AwardAwarding OrganizationDate
Abstract ScholarshipAmerican Thoracic Society, Respiratory Cell Molecular Biology Assembly2016
Abstract ScholarshipAmerican Thoracic Society, Thoracic Oncology Assembly2015
Abstract ScholarshipAmerican Thoracic Society, Allergy, Immunology and Inflammation Assembly2014
Junior Investigator AwardAAP/ASCI (American Association of Physicians/ American Society of Clinical investigators)2011
RNA Society Fellowship of BBSRCBitechnology and Biological Sciences Research Council2005
Graduate School AwardUniversity of Queensland2000
Postgraduate Research ScholarshipUniversity of Queensland1998

Professional Service

OrganizationRoleDate
FASEBReviewer2017 - Present
European Respiratory JournalReviewer2017 - Present
American Thoracic Society International Conference, Poster Discussion Session: “MicroRNAs, RNAseq, LncRNA: Biology and Function"Chair2016
American Journal of Physiology / Lung Cellular and Molecular PhysiologyReviewer2016 - Present
American Journal of Respiratory and Critical Care MedicineReviewer2016 - Present
Journal of Cell BiologyReviewer2015 - Present
Molecular MedicineReviewer2015 - Present
Pulmonary Medicine and Respiratory ResearchEditor2015 - Present
Neuroscience LettersReviewer2014
Journal of Clinical ImmunologyReviewer2013

Departments & Organizations