Shervin Takyar, MD, PhD

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.