Academic Title:
Associate Professor
Primary Appointment:
Medicine
Administrative Title:
Director of the Lung and Critical Care Tissue Bank; Associate Program Director for Research, Pulmonary and Critical Care Fellowship Program
Email:
Location:
20 Penn St., HSRFII, room S022A, Baltimore, MD, 21201
Education and Training
National University of Uzbekistan named after Mirzo Ulugbek, BS, Environmental Sciences, 2005
Gyeongsang National University, MS/PhD, Neurobiology, 2010
Brigham & Women's Hospital, Harvard Medical School, Postdoctoral Study, Inflammation and Interstitial Lung Diseases (ILDs), 2017
Biosketch
Dr. Tsoyi is a PhD scientist with expertise in lung biology and organ fibrosis.
Dr. Tsoyi engages various techniques, such as single-cell and spatial transcriptomics, to better understand the molecular intricacies driving the pathobiology of chronic lung disorders.
My current research focuses on understanding the role of different types of endocytosis, including macropinocytosis, on the development of profibrotic responses in lung fibroblasts.
Research/Clinical Keywords
Interstitial Lung Disease, Pulmonary Fibrosis, Fibroblasts, Molecular Biology,
Highlighted Publications
- Tsoyi K, Liang X, De Rossi G, Ryter SW, Xiong K, Chu SG, Liu X, Ith B, Celada LJ, Romero F, Robertson MJ, Esposito AJ, Poli S, El-Chemaly S, Perrella MA, Shi Y, Whiteford J, Rosas IO. CD148 Deficiency in Fibroblasts Promotes the Development of Pulmonary Fibrosis. Am J Respir Crit Care Med. 2021;204(3):312-25. doi: 10.1164/rccm.202008-3100OC. PubMed PMID: 33784491; PMCID: PMC8513593.
- Tsoyi K, Chu SG, Patino-Jaramillo NG, Wilder J, Villalba J, Doyle-Eisele M, McDonald J, Liu X, El-Chemaly S, Perrella MA, Rosas IO. Syndecan-2 Attenuates Radiation-induced Pulmonary Fibrosis and Inhibits Fibroblast Activation by Regulating PI3K/Akt/ROCK Pathway via CD148. Am J Respir Cell Mol Biol. 2018;58(2):208-15. doi: 10.1165/rcmb.2017-0088OC. PubMed PMID: 28886261; PMCID: PMC5805997.
- Tsoyi K, Hall SR, Dalli J, Colas RA, Ghanta S, Ith B, Coronata A, Fredenburgh LE, Baron RM, Choi AM, Serhan CN, Liu X, Perrella MA. Carbon Monoxide Improves Efficacy of Mesenchymal Stromal Cells During Sepsis by Production of Specialized Proresolving Lipid Mediators. Crit Care Med. 2016;44(12):e1236-e45. doi: 10.1097/CCM.0000000000001999. PubMed PMID: 27513357; PMCID: PMC5113254.
Research Interests
I have a strong background in immunology and molecular biology. My Ph.D. thesis focused on understanding the role of phosphatase and tensin homolog (PTEN) in regulating vascular inflammation. Then, I joined Dr. Perrella’s laboratory for a postdoctoral fellowship in the fields of sepsis and sepsis-mediated immunosuppression at Brigham and Women’s Hospital (BWH) and Harvard Medical School (HMS). In 2015, I joined Dr. Rosas’ laboratory as a senior research fellow. In Dr. Rosas’ laboratory, I have been focused on understanding autoimmune-mediated interstitial lung disorders such as rheumatoid arthritis-interstitial lung disease (RA-ILD). Currently, my laboratory is focusing on several projects:
Project 1: Define the role of macropinocytosis in autoimmune and fibrotic disorders.
Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid with the components contained therein. Macropinocytosis has been shown to play a prominent role in the survival, migration, and invasion of malignant cells by providing crucial extracellular nutrients (e.g., free amino acids, polypeptides, and fatty acids). My central hypothesis is that increased macropinocytosis promotes the development of dermal (scleroderma/systemic sclerosis) and lung fibrosis (idiopathic pulmonary fibrosis/IPF). Thus, its inhibition exerts anti-fibrotic effects in the animal models of skin and pulmonary fibrosis by reducing profibrotic responses in activated fibroblasts.
Project 2: Define the role of non-canonical Wnt signaling in fibrotic disorders.
The Wnt pathway plays essential roles in development, tissue homeostasis and disease, by transducing signals from 19 Wnt ligands via a complex network of receptors and co-receptors. Wnt signaling can be classified into canonical (β-catenin-dependent) and non-canonical (β-catenin-independent) Wnt signaling. The canonical pathway is associated with the transport of β-catenin to the nucleus upon Wnt binding to the Frizzled (Fz or Fzd) receptor and has been extensively studied in various fibrotic disorders. Whereas the importance of non-canonical Wnt signaling is not fully understood. In this project, we attempt to cover this gap in knowledge by exploitng conditional knock out mice and primary cell culture techniques.
Project 3: Define the role of protein palmitoylation and depalmitoylation in fibrotic disorders.
Protein palmitoylation, also known as lipidation or S-acylation, is a reversible post-translational modification of cysteine residues with long-chain fatty acids, mainly palmitic acid. In mammalian cells, protein palmitoylation is a balancing act of two groups of enzymes: zDHHC-type palmitoyltransferases that catalyze the addition of fatty acid chains to proteins, while acyl-protein thioesterases (APTs) reverse this reaction. Although the role of protein palmitoylation has been studied in various disorders such as cancer and inflammation, its role in fibroblast activation and organ fibrosis is poorly understood. Currently, we are trying to evaluate the impact of different zDHHCs and APTs in the progression of IPF and SSc-ILD. We are also employing proteomics to determine the levels of protein palmitoylation in normal and fibrotic conditions.
Awards and Affiliations
Full Scholarship award from Ministry of Higher Education, Uzbekistan for study at National University of Uzbekistan named after Mirzo Ulugbek, in view of excellent academic performance in high school, 2001
Post-doctoral scholarship award from Brain Korea 21 foundation, 2010
Grants and Contracts
Active:
R01 HL176934: “Macropinocytosis and Pulmonary Fibrosis”, 2025 – 2028, National Heart, Lung and Blood Institute, role PI
Completed:
K01 AR074558: “Antifibrotic effects of Syndecan-2 and CD148 in Rheumatoid Arthritis Interstitial Lung Disease”, 2020 - 2025, National Institute of Arthritis, Musculoskeletal and Skin Diseases, role PI.
R21 AR080332 “Contribution of macropinocytosis in fibroblast activation and systemic sclerosis”, 2022-2023, National Institute of Arthritis, Musculoskeletal and Skin Diseases, role PI.
W81XWH2210147 (Discovery Award), “Anti-fibrotic effects of macropinocytosis inhibition in Idiopathic Pulmonary Fibrosis", 2022-2024, Department of Defense, role PI.