Lin Liu

Lin Liu, Ph.D., FAPS, received his Ph.D. in Biochemistry from the Chinese Academy of Sciences and completed his postdoctoral training at the University of Pennsylvania. He began his academic career as a faculty member at East Carolina University before joining the OSU College of Veterinary Medicine as Associate Professor of Physiological Sciences. Dr. Liu was subsequently promoted to Full Professor and appointed as Lundberg-Kienlen Endowed Professor/Chair in Biomedical Research and a Regents Professor. He was also selected as a Riata Faculty Fellow in the OSU School of Entrepreneurship and elected as a Fellow of the American Physiological Society.

Dr. Liu is the Founding Director of the Oklahoma Center for Respiratory and Infectious Diseases and the Interdisciplinary Program in Regenerative Medicine at OSU. He also leads the Lung Diseases and Infection Laboratory. Over the years, Dr. Liu has developed a nationally recognized research program focused on respiratory and infectious diseases. His current research interests include host-respiratory pathogen interactions (e.g. SARS-CoV-2, influenza virus, and Mycobacterium tuberculosis); the pathogenesis of pulmonary diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary diseases (COPD); and stem cell-based therapy and human tissue engineering. As Principal Investigator, Dr. Liu has secured over $48 million in grant funding (as December 2024) from federal agencies such as the National Institutes of Health and the U.S. Department of Agriculture, foundations including American Heart Association and March of Dimes, and various local organizations.

Dr. Liu has contributed extensively to the scientific community, serving on NIH and other grant review panels and chairing the OSU Biomedical Sciences Group of the Graduate Faculty Council. He has also been a member of the Steering Committee for the Physiological Genomics Interest Group of the American Physiological Society. A dedicated mentor, Dr. Liu has a distinguished record of training and mentoring early-career scientists. His achievements have been recognized with numerous awards including the Pfizer Award for Research Excellence and the OSU Regents Distinguished Research Award.

Research Interests

Our research programs aim to understand the pathogenesis of respiratory and infectious diseases and to develop diagnostic tools and therapeutics for these conditions. The diseases we study include non-infectious conditions such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary diseases (COPD), as well as infectious diseases like influenza, COVID-19 and tuberculosis. 

Our research projects are organized into 3 interrelated areas: respiratory infection, pathogenesis of pulmonary diseases, and stem cell therapy and tissue engineering. The work in our laboratory spans multiple levels from gene-level studies to whole-animal models. Key techniques employed include bulk and single cell RNA sequencing, spatial transcriptomics, genome-wide CRISPR library screen, CRISPR/Cas9 gene editing, RNA interference, real-time PCR, cloning, biochemical, molecular and cellular techniques, and various animal models.

1. Host-pathogen Interactions during Respiratory Infection

Respiratory Viral Infection

Respiratory infections are among the most prevalent disease burdens worldwide and are recognized as a critical public health priority. Influenza virus causes annual epidemics and periodic pandemics, resulting in millions of deaths. The pandemic of coronavirus disease 2019 (COVID-19) has caused hundreds of million infections and several million fatalities globally. The high mutation rate of respiratory viruses presents a significant challenge, as it often leads to widespread resistance to antiviral drugs viral proteins.

To address this, our research focuses on understanding the molecular mechanisms by which host factors regulate influenza virus and SARS-CoV-2 replication. By targeting these host factors, we aim to develop antiviral drugs that circumvent mutagenesis-associated viral escape.    

•  Non-coding RNAs in respiratory infection. We are particularly interested in the roles of non-coding RNAs, including microRNAs, circular RNAs and long non-coding RNAs (lncRNAs) in respiratory infections. MicroRNAs (~21-23 nucleotides) and lncRNAs (>200 nucleotides) are increasingly recognized for their roles in regulating various biological processes and diseases. MicroRNAs predominantly control gene expression at the post-transcriptional level while lncRNAs regulate gene expression through interactions with RNA, DNA and proteins, influencing processes such as transcription, splicing, mRNA stability, and translation. Our approaches include target gene identification using expression library screening, genome-wide CRISPR library screening, and transcriptome analysis integrated with computational methods, followed by functional, mechanistic, and animal studies.       
•  Targeting cellular signaling pathways for antiviral therapeutics. We are also exploring critical components in cellular signaling pathways as potential therapeutic targets. A key focus is on ADP-ribosylation, a post-translational modification that plays a crucial role in cellular processes and NAD metabolomes. We identify lead compounds targeting these pathways and evaluate their mechanisms of action. Additional studies include assessing efficacy in animal models, toxicity and safety profiles, and pharmacokinetics with an ultimate goal of Investigational New Drug (IND) applications   
•  Post COVID-19 lung injury and fibrosis. Our recent work investigates the contribution of trained innate immunity, epigenetic modifications, and lung stem cells to post COVID-19 lung injury and fibrosis. This research aims to uncover mechanisms underlying long-term complications of COVID-19 and identify novel therapeutic strategies.

Respiratory Bacterial Infection 

Tuberculosis remains a major global challenge, with nearly 10 million active cases and 1.4 million deaths annually. Our research focuses on understanding the host-pathogen interactions in TB and developing innovative therapeutic strategies.

•  Anti-lncRNAs in tuberculosis. In collaboration with Dr. Yong Cheng in the Department of Biochemistry and Molecular Biology at OSU, this project aims to identify anti-lncRNAs that counteract Mycobacterium tuberculosis (M. tb) infection. Using a genome-wide CRISPR activation screen, we seek to uncover lncRNAs with therapeutic potential and develop them as host-directed therapies for TB. We are also investigating the interaction between circular RNAs and M. tb.
•  ADP ribosylation in host-M. tb interaction. This project explores the role of ADP ribosylation in modulating the interaction between host and M. tb.
•  Iron metabolism and immunometabolism. We study the connection between iron metabolism, immunometabolism, and M. tb infection.     
•  Post-TB lung diseases. This project focuses on the long-term consequences of TB, particularly post-TB pulmonary fibrosis. 

2. Pathogenesis of Pulmonary Diseases

Our research in this area addresses several critical lung diseases, including Acute Respiratory Distress Syndrome (ARDS)/Acute Lung injury (ALI), Idiopathic Pulmonary Fibrosis (IPF), Chronic Obstructive Pulmonary Disease (COPD) and Bronchopulmonary Dysplasia (BPD). One of our current focuses is IPF. IPF is a chronic interstitial fibrotic lung disease affecting 200,000 Americans annually, with a median survival of 3-5 years from diagnosis. Lung tissue scarring (fibrosis) impairs oxygen transmission to the blood and other organs, often leading to respiratory failure. The disease predominantly affects adults aged 50 to 70 years. Although the FDA has recently approved two drugs, pirfenidone and nintedanib to slow the decline in lung function, these treatments do not cure the disease. Effective curative therapies for IPF remain unavailable. 

The pathological hallmark of IPF is the formation of fibroblastic foci – clusters of activated and proliferating fibroblasts (myofibroblasts) that deposit excessive extracellular matrix, leading to pulmonary fibrosis. The proliferation and activation of resident fibroblasts are considered the major contributors to IPF pathogenesis. Our projects investigate the following key aspects of IPF.

•  Non-coding RNAs and cellular signaling. We explore the regulatory roles of microRNAs, circular RNAs and long non-coding RNAs in lung fibroblast cellular signaling pathways.
•  Iron and IPF. We investigate the contribution of iron metabolism to the progression of pulmonary fibrosis.
•  Ferroptosis in epithelial cells. We examine the role of ferroptosis (iron-dependent cell death) in lung epithelial cells and its contribution to IPF pathology.
•  Lymphatic vessels in IPF. We study the involvement of lymphatic vessels in IPF progression and their potential as therapeutic targets.

3. Stem Cell Therapy and Tissue Engineering

Stem Cell Therapy

Stem cell-based therapy and tissue engineering hold immense potential for repairing or regenerating damaged lung tissue, offering promising approaches to treat and potentially cure lung diseases. Various types of stem cells, including embryonic stem cells (ESCs), bone-marrow-derived mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), can be employed for these purposes.

Our research in stem cell therapy focuses on engineering MSCs and iPSCs to improve treatment outcomes for lung diseases. Epithelial cell damage is a common feature in many pulmonary diseases such as IPF, COPD, ARDS and influenza or bacterial pneumonia. Our objectives are twofold:

•  Enhancing alveolar epithelial repair by promoting the differentiation of MSCs or iPSC into alveolar epithelial cells and stimulating endogenous stem cells within the lung to regenerate epithelial cells.     
•  Reversing pathological process through modulating the stem cell secretome and exosome-mediated transfer of therapeutic molecules from stem cells to lung cells to mitigate fibrosis, inflammation, and viral or bacterial replication

Tissue Engineering

We aim to advance tissue engineering to build human lung tissue models for translation research. Current investigations often rely on 2D cell cultures and mouse models, which fail to adequately replicate human lung physiology and pathology. This limitation hinders translational research and contributes to the high failure rate of drug candidates in clinical trials.

Our goal is to create renewable, patient-specific 3D human lung tissue models using iPSCs- or MSCs-derived lung cells. These tissue-engineered models can accurately mimic normal and diseased human lung tissue, serve as platforms for mechanistic and translational studies, facilitate the testing of drug safety and efficacy and enable high-throughput screening of therapeutic candidates.

LAB MEMBERS

Lin Liu. Ph.D., FAPS., Regents Professor, Lundberg-Kienlen Endowed Chair and Director

Chaoqun Huang, Ph.D., M.D.,Research Associate Professor

Yurong Liang, Ph.D., Research Assistant Professor and Lab Manager

Kishore Vaddadi, Ph.D., Research Assistant Professor

Rajakumar Thangarasu, Ph.D., Postdoctoral Fellow

Firoz Ahmed, Ph.D., Postdoctoral Fellow

Quanjin Dang, Ph.D. student 

Akshaya Surendran, Ph.D. student

Keerthana Santhosh, Ph.D. student

Prince Jhandai, Ph.D. student

Adam Soriano, Ph.D. student

Elizabeth Varghese, Ph.D. student

Nazmul Haque, Ph.D. student

Dharanya Muthiah, Ph.D. student

Pavan Nagdev, Ph.D. student