B.S. Bioscience, The College of Life Sciences, Nankai University, Tianjin, China, 2007

Ph.D.   Biochemistry and Molecular Biology (PhD advisor: Dr. Hao Ying),  Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China, 2014

Pulmonary Diseases, Immunology, Sepsis, Chronic Obstructive Pulmonary Disease (COPD)

Outstanding Student Awards of Nankai University, 2006

Outstanding Student Awards of Chinese Academy of Sciences, 2010

Presentation Award-Academic Conference of Shanghai Institutes for Biological Sciences, 2011

First Class Fellowship Award from Postdoctoral Science Foundation of China, 2015

Distinguished Young Scholars Award from National Science Foundation of China, 2016

Poster Award – Pittsburgh-Munich International Lung Conference, 2016

American Thoracic Society, Member, 2015-present

American Heart Association, Member,  2019-present

Our group focuses on developing innovative basic and translational studies, which will expand our understanding of the genes involved in the pathogenies of pneumonia. Specifically, we are trying to address the scientific questions: how these genes are regulated and what their roles are during bacterial infection. In the long term, our group will develop novel approaches and technologies to help prevent, diagnose, and cure of patients with pneumonia.

Our ongoing work is focused on innate immunity and bacterial pneumonia:

(1) Mammalian genomes encode thousands of long non-coding RNAs (lncRNAs). LncRNAs are extensively expressed in various immune cells including the monocytes, and macrophages. Our research aims to investigate the regulation and function of long non-coding RNA in macrophages during bacterial-induced pneumonia. This study potentially will help to identify novel mechanisms and/or therapeutic strategies for lung inflammation and injury.

(2) Depression of thyroid function is often observed in patients in ICU, which is characterized by decreased blood total triiodothyronine (T3) and free T3.  Although thyroid dysfunction seems to be associated with a worse prognosis, it is still unclear whether this alteration is a protective adaption or maladaptive response.  We will investigate microRNA-mediated thyroid hormone action in macrophage maturation and activation. Successful completion of the proposed studies might provide fundamental knowledge of TH action in the innate immune system.

(3) It is well known that EV is secreted as a cell-to-cell communication mediator in physiological and pathological scenarios. In our further studies, we will perform translational studies to explore the EV component as diagnostics for lung diseases. Additionally, our group will continue the investigation of EV-based targeted delivery technology.

Other Research Interests

Sepsis, Chronic Obstructive Pulmonary Disease (COPD)

1. Zhang D, Lee H, Wang X, Groot M, Sharma L, Dela Cruz CS, Jin Y. A potential role of microvesicle-containing miR-223/142 in lung inflammation. Thorax. 2019. doi: 10.1136/thoraxjnl-2018-212994. PubMed PMID: 31331947.
2. Lee H, Li C, Zhang Y, Zhang D, Otterbein LE, Jin Y. Caveolin-1 selectively regulates microRNA sorting into microvesicles after noxious stimuli. J Exp Med. 2019. doi: 10.1084/jem.20182313. PubMed PMID: 31235510.
3. Wang X, Rojas-Quintero J, Wilder J, Tesfaigzi Y, Zhang D, Owen CA. Tissue Inhibitor of Metalloproteinase-1 Promotes Polymorphonuclear Neutrophil (PMN) Pericellular Proteolysis by Anchoring Matrix Metalloproteinase-8 and -9 to PMN Surfaces. J Immunol. 2019. doi: 10.4049/jimmunol.1801466. PubMed PMID: 31019060.
4. Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S, Li P, Zhang S, Sun C, Wu Y, Yu S, Li X, Zhang H, Qian H, Zhang D, Guo F, Zhai Q, Ding Q, Wang L, Ying H. microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci U S A. 2018. doi: 10.1073/pnas.1803377115. PubMed PMID: 30373812.
5. Zhang D, Lee H, Wang X, Rai A, Groot M, Jin Y. Exosome-Mediated Small RNA Delivery: A Novel Therapeutic Approach for Inflammatory Lung Responses. Mol Ther. 2018;26(9):2119-30. doi: 10.1016/j.ymthe.2018.06.007. PubMed PMID: 30005869; PMCID: PMC6127502.
6. Lee H, Zhang D, Laskin DL, Jin Y. Functional Evidence of Pulmonary Extracellular Vesicles in Infectious and Noninfectious Lung Inflammation. J Immunol. 2018. doi: 10.4049/jimmunol.1800264. PubMed PMID: 29997122.
7. Polverino F, Rojas-Quintero J, Wang X, Petersen H, Zhang L, Gai X, Higham A, Zhang D, Gupta K, Rout A, Yambayev I, Pinto-Plata V, Sholl LM, Cunoosamy D, Celli BR, Goldring J, Singh D, Tesfaigzi Y, Wedzicha J, Olsson H, Owen CA. A Disintegrin and A Metalloproteinase Domain-8 (ADAM8): A Novel Protective Proteinase in COPD. Am J Respir Crit Care Med. 2018. doi: 10.1164/rccm.201707-1331OC. PubMed PMID: 29750543.
8. Wang X, Polverino F, Rojas-Quintero J, Zhang D, Sanchez J, Yambayev I, Lindqvist E, Virtala R, Djukanovic R, Davies DE, Wilson S, O’Donnell R, Cunoosamy D, Hazon P, Higham A, Singh D, Olsson H, Owen CA. A Disintegrin and A Metalloproteinase-9 (ADAM9): A Novel Proteinase Culprit with Multifarious Contributions to COPD. Am J Respir Crit Care Med. 2018. doi: 10.1164/rccm.201711-2300OC. PubMed PMID: 29864380.
9. Zhang D*, Lee H*, Zhu Z, Minhas JK, Jin Y. Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol. 2017;312(1):L110-L21. doi: 10.1152/ajplung.00423.2016. PubMed PMID: 27881406; PMCID: PMC5283929.
10. Zhu Z, Zhang D, Lee H, Menon AA, Wu J, Hu K, Jin Y. Macrophage-derived apoptotic bodies promote the proliferation of the recipient cells via shuttling microRNA-221/222. J Leukoc Biol. 2017;101(6):1349-59. doi: 10.1189/jlb.3A1116-483R. PubMed PMID: 28274991; PMCID: PMC5433853.
11. Zhang D, Lee H, Haspel JA, Jin Y. Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis via sponging microRNA-150. FASEB J. 2017;31(10):4472-81. doi: 10.1096/fj.201700091R. PubMed PMID: 28655711; PMCID: PMC5602897.
12. Lee H, Zhang D, Wu J, Otterbein LE, Jin Y. Lung Epithelial Cell-Derived Microvesicles Regulate Macrophage Migration via MicroRNA-17/221-Induced Integrin beta1 Recycling. J Immunol. 2017;199(4):1453-64. doi: 10.4049/jimmunol.1700165. PubMed PMID: 28674181; PMCID: PMC5561736.
13. Cao Y, Zhang D, Moon HG, Lee H, Haspel JA, Hu K, Xie L, Jin Y. MiR-15a/16 Regulates Apoptosis of Lung Epithelial Cells after Oxidative Stress. Mol Med. 2016;22. doi: 10.2119/molmed.2015.00136. PubMed PMID: 27257854; PMCID: PMC5023515.
14. Zhang D, Lee H, Cao Y, Dela Cruz CS, Jin Y. miR-185 mediates lung epithelial cell death after oxidative stress. Am J Physiol Lung Cell Mol Physiol. 2016;310(7):L700-10. doi: 10.1152/ajplung.00392.2015. PubMed PMID: 26747785; PMCID: PMC4824162.
15. Lee H*, Zhang D*, Zhu Z, Dela Cruz CS, Jin Y. Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs. Sci Rep. 2016;6:35250. doi: 10.1038/srep35250. PubMed PMID: 27731391; PMCID: PMC5059671.
16. Ye C, Zhang D, Zhao L, Li Y, Yao X, Wang H, Zhang S, Liu W, Cao H, Yu S, Wang Y, Jiang J, Wang H, Li X, Ying H. CaMKK2 Suppresses Muscle Regeneration through the Inhibition of Myoblast Proliferation and Differentiation. Int J Mol Sci. 2016;17(10). doi: 10.3390/ijms17101695. PubMed PMID: 27783047; PMCID: PMC5085727.
17. Zhang D*, Li Y*, Yao X, Wang H, Zhao L, Jiang H, Yao X, Zhang S, Ye C, Liu W, Cao H, Yu S, Wang YC, Li Q, Jiang J, Liu Y, Zhang L, Liu Y, Iwai N, Wang H, Li J, Li J, Li X, Jin ZB, Ying H. miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle. Cell Rep. 2016;16(3):757-68. doi: 10.1016/j.celrep.2016.06.040. PubMed PMID: 27396327.
18. Li Y, Zhang D, Wang X, Yao X, Ye C, Zhang S, Wang H, Chang C, Xia H, Wang YC, Fang J, Yan J, Ying H. Hypoxia-inducible miR-182 enhances HIF1alpha signaling via targeting PHD2 and FIH1 in prostate cancer. Sci Rep. 2015;5:12495. doi: 10.1038/srep12495. PubMed PMID: 26205124; PMCID: PMC4513346.
19. Lee SJ, Zhang M, Hu K, Lin L, Zhang D, Jin Y. CCN1 suppresses pulmonary vascular smooth muscle contraction in response to hypoxia. Pulm Circ. 2015;5(4):716-22. doi: 10.1086/683812. PubMed PMID: 26697179; PMCID: PMC4671746.
20. Yao X, Sa R, Ye C, Zhang D, Zhang S, Xia H, Wang YC, Jiang J, Yin H, Ying H. Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach. Prostaglandins Other Lipid Mediat. 2015;118-119:11-8. doi: 10.1016/j.prostaglandins.2015.03.005. PubMed PMID: 25841349.
21. Jing Y, Liu W, Cao H, Zhang D, Yao X, Zhang S, Xia H, Li D, Wang YC, Yan J, Hui L, Ying H. Hepatic p38alpha regulates gluconeogenesis by suppressing AMPK. J Hepatol. 2015;62(6):1319-27. doi: 10.1016/j.jhep.2014.12.032. PubMed PMID: 25595884.
22. Li X, Li Y, Zhao L, Zhang D, Yao X, Zhang H, Wang YC, Wang XY, Xia H, Yan J, Ying H. Circulating Muscle-specific miRNAs in Duchenne Muscular Dystrophy Patients. Mol Ther Nucleic Acids. 2014;3:e177. doi: 10.1038/mtna.2014.29. PubMed PMID: 25050825; PMCID: PMC4121518.
23. Yao X, Hou S, Zhang D, Xia H, Wang YC, Jiang J, Yin H, Ying H. Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver. Cell Biosci. 2014;4:38. doi: 10.1186/2045-3701-4-38. PubMed PMID: 25105012; PMCID: PMC4124172.
24. Zhang D, Wang X, Li Y, Zhao L, Lu M, Yao X, Xia H, Wang YC, Liu MF, Jiang J, Li X, Ying H. Thyroid hormone regulates muscle fiber type conversion via miR-133a1. J Cell Biol. 2014;207(6):753-66. doi: 10.1083/jcb.201406068. PubMed PMID: 25512392; PMCID: PMC4274265.
25. Liu W, Cao H, Ye C, Chang C, Lu M, Jing Y, Zhang D, Yao X, Duan Z, Xia H, Wang YC, Jiang J, Liu MF, Yan J, Ying H. Hepatic miR-378 targets p110alpha and controls glucose and lipid homeostasis by modulating hepatic insulin signalling. Nat Commun. 2014;5:5684. doi: 10.1038/ncomms6684. PubMed PMID: 25471065.
26. Wang YC, Li Y, Wang XY, Zhang D, Zhang H, Wu Q, He YQ, Wang JY, Zhang L, Xia H, Yan J, Li X, Ying H. Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity. Diabetologia. 2013;56(10):2275-85. doi: 10.1007/s00125-013-2996-8. PubMed PMID: 23868745.
27. Zhang D, Li X, Chen C, Li Y, Zhao L, Jing Y, Liu W, Wang X, Zhang Y, Xia H, Chang Y, Gao X, Yan J, Ying H. Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration. PLoS One. 2012;7(7):e41478. doi: 10.1371/journal.pone.0041478. PubMed PMID: 22911796; PMCID: PMC3404058.

NIH/NHLBI R00 HL141685–06/20/2020 – 05/31/2023

Title: Lincenc1 regulates the lipopolysaccharide-induced inflammatory response in macrophages

The goal of this project is to investigate the regulation and function of an uncharacterized long non-coding RNA, called Lincenc1 in macrophage in response to infectious stimulation, such as LPS or bacteria.

Role: PI

NIH/NIAID R03 AI152003–03/16/2020 – 02/28/2022

Title: Thyroid Hormone Regulates Immune Response of Macrophages in Sepsis

The major goals of this project are to develop an innovative way of thyroid hormone replacement using extracellular vesicles as a therapeutic strategy for sepsis.

Role: PI

NIH/NHLBI K99 HL141685–04/15/2018 – 04/15/2020

Title: Lincenc1 regulates the lipopolysaccharide-induced inflammatory response in macrophages

The goal of this project is to investigate the regulation and function of an uncharacterized long non-coding RNA, called Lincenc1 in macrophage in response to infectious stimulation, such as LPS or bacteria.

Role: PI