Lin Lab

Dr. Zhiqiang Lin's research centers on basic molecular mechanisms that govern organ and tissue growth, as well as understanding cellular responses to disease-induced stress.

News From The Lin Lab

The American Heart Association Awards Research Grant to MMRI Scientist Investigating Fatty Liver Disease

The American Heart Association (The Association) recently awarded a $300,000 grant to support a project led by Principal Investigator, Zhiqiang Lin, Ph.D., associate professor of biomedical research and translational medicine at Masonic Medical Research Institute (MMRI), to investigate new ways to protect the liver and in turn, the heart, from those with fatty and fibrotic liver, known as the Metabolic Dysfunction Associated Steatotic Hepatitis (MASH).

READ FULL STORY HERE

Areas of Investigation

Dr. Lin employs genetics as a powerful tool to investigate the intricate impacts of various stressors, including inflammation, obesity, and COVID-19, on the functionality of heart, liver and adipose tissue. He conducts tissue-specific gene gain- and loss-of-function studies, specifically focusing on unraveling the pathophysiological roles of the Hippo-YAP pathway in the heart and brown adipose tissue. Leveraging cutting-edge technology, such as Adenovirus-associated-virus (AAV) and modified messenger RNA, as gene delivery platforms, Dr. Lin's translational studies aim to develop promising drug candidates for the treatment of cardiovascular and metabolic diseases.

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Lab Focus

Hippo-YAP Signaling: Heart and Fat Tissue Function

medical Science lab testing

The Hippo-YAP signaling is an integrative pathway that controls organ growth, metabolism, and innate/adaptive immunity. Dr. Lin uses the Hippo-YAP pathway as a probe to investigate how organs respond to developmental signals and disease stresses, with a focus on heart, liver and brown adipose tissue. His long-term goal is to seek fundamental knowledge to deepen our understanding of these organs and to inform the efforts of reducing cardiovascular diseases and obesity.

Covid-19 Spike Protein: Immunity and Heart Health

Dr. Lin had a breakthrough study indicating that the spike protein from SARS-CoV-2 causes heart muscle damage. He was the first to discover the mechanisms by which this might occur. His research indicates that the defense against the invasion of the SARS-CoV-2 pathogen is natural immunity, and heart muscle cells have their own immune machinery. However, COVID-19 infections cause an immune response that may also impair heart muscle cell function. Furthermore, Dr. Lin's ongoing investigations delve into the molecular mechanism of long COVID on a myriad of cell types, further expanding our understanding of the multifaceted impacts of this novel disease.

Testing spike routine

Metabolism: Research on Live and Brown Adipose Tissue

lab tech in a Science lab

Brown fat, also known as brown adipose tissue, which is a special type of fat that “turns on” (becomes activated) when you get cold stress, to help maintain body temperature. Importantly, brown fat is a biological fuel that can increase the metabolic rate, decrease fat storage and thereby, lower one’s propensity for developing obesity.  Dr. Lin’s research discovered that brown fat continues to grow after birth. He is working to identify the developmental signals responsible for the growth of brown fat cells and determining whether they can be manipulated through gene expression to generate more.

Dr. Lin has already been awarded a patent (Patent No. US 11,319, 354 B2). In this patent, a brown adipose tissue specific gene therapy reagent is used to reduce high fat diet induced obesity.

Dr. Lin has recently filed another patent, which uses a gene therapy approach to treat Nonalcoholic steatohepatitis (NASH).

Investigation of Diseases

Dr. Zhiqiang Lin's research centers on basic molecular mechanisms to study:

  • Cardiovascular diseases
  • Obesity
  • Covid-19
  • Inflammation
  • Retina regeneration
  • Nonalcoholic steatohepatitis (NASH)
Test tube wth liquid
lin Zhiqiang headshot

Meet Dr. Zhiqiang Lin

Associate Professor
Biomedical Research and Translational Medicine

zlin@mmri.edu

Dr. Lin received his Ph.D. from Peking University in 2008, and joined William T. Pu’s lab in 2009 as a postdoc. In 2013, Dr. Lin was appointed as an instructor and started building up his research projects. In 2018, Dr. Lin was recruited to MMRI as an assistant professor and principal investigator. Since then, Dr. Lin has developed projects related to cardiovascular diseases and obesity. The long-term goal of the Lin lab is to understand the basic molecular mechanisms controlling organ/tissue growth and to apply the newly acquired knowledge for reducing cardiovascular diseases and obesity.

Lab Members

Lin Chen Headshot

Lin Chen, Ph.D.

Visiting Scholar

Chen holds a Ph.D. in Biology from Northwest University, Shaanxi, China. Chen has over 20 years of experience in microbiology research and molecular microbiological technology. Chen joined MMRI in 2025 and focuses on metabolism related research.

Past Members

Jessica Freed, Summer 2019
Alyssa Reese, Summer 2019
Madeline Walters, 2019-2020
Steven Negron, 2019-2022
Yunan Gao, 2020-2021
Caroline Sheldon, 2021-2022
Nikita Shah, Summer 2023
Amanda Davenport, 2022-2024
Aaron Farley, 2022-2025
Gianna Frank, Summer 2024
Houze Li, Summer 2024
Genyu Wang, Ph.D., 2024-2025
Angelina Tangorra, Summer 2025

Publications

  1. Davenport, A, Kessinger, CW, Pfeiffer, RD, Shah, N, Xu, R, Abel, ED et al.. Comparative analysis of two independent Myh6-Cre transgenic mouse lines. J Mol Cell Cardiol Plus. 2024;9 :. doi: 10.1016/j.jmccpl.2024.100081. PubMed PMID:39323506 PubMed Central PMC11423776.
  2. Farley, A, Gao, Y, Sun, Y, Zohrabian, S, Pu, WT, Lin, Z et al.. Activation of VGLL4 Suppresses Cardiomyocyte Maturational Hypertrophic Growth. Cells. 2024;13 (16):. doi: 10.3390/cells13161342. PubMed PMID:39195232 PubMed Central PMC11352427.
  3. Lin, Z. More than a key-the pathological roles of SARS-CoV-2 spike protein in COVID-19 related cardiac injury. Sports Med Health Sci. 2023;6 (3):209-20. doi: 10.1016/j.smhs.2023.03.004. PubMed PMID:37361919 PubMed Central PMC10062797.
  4. Sheldon, C, Kessinger, CW, Sun, Y, Kontaridis, MI, Ma, Q, Hammoud, SS et al.. Myh6 promoter-driven Cre recombinase excises floxed DNA fragments in a subset of male germline cells. J Mol Cell Cardiol. 2023;175 :62-66. doi: 10.1016/j.yjmcc.2022.12.005. PubMed PMID:36584478 PubMed Central PMC9974737.
  5. Sheldon, C, Farley, A, Ma, Q, Pu, WT, Lin, Z. Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development. Cells. 2022;11 (18):. doi: 10.3390/cells11182832. PubMed PMID:36139407 PubMed Central PMC9496954.
  6. He, X, Liu, J, Gu, F, Chen, J, Lu, YW, Ding, J et al.. Cardiac CIP protein regulates dystrophic cardiomyopathy. Mol Ther. 2022;30 (2):898-914. doi: 10.1016/j.ymthe.2021.08.022. PubMed PMID:34400329 PubMed Central PMC8822131.
  7. Gao, Y, Sun, Y, Ercan-Sencicek, AG, King, JS, Akerberg, BN, Ma, Q et al.. YAP/TEAD1 Complex Is a Default Repressor of Cardiac Toll-Like Receptor Genes. Int J Mol Sci. 2021;22 (13):. doi: 10.3390/ijms22136649. PubMed PMID:34206257 PubMed Central PMC8268263.
  8. Negron, SG, Xu, B, Lin, Z. Isolating Brown Adipocytes from Murine Interscapular Brown Adipose Tissue for Gene and Protein Expression Analysis. J Vis Exp. 2021; (169):. doi: 10.3791/62332. PubMed PMID:33779621 .
  9. Negron, SG, Ercan-Sencicek, AG, Freed, J, Walters, M, Lin, Z. Both proliferation and lipogenesis of brown adipocytes contribute to postnatal brown adipose tissue growth in mice. Sci Rep. 2020;10 (1):20335. doi: 10.1038/s41598-020-77362-x. PubMed PMID:33230135 PubMed Central PMC7683731.
  10. Guo, H, Lu, YW, Lin, Z, Huang, ZP, Liu, J, Wang, Y et al.. Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart. Nat Commun. 2020;11 (1):4666. doi: 10.1038/s41467-020-18379-8. PubMed PMID:32938943 PubMed Central PMC7494909.
  11. Wang, S, Li, Y, Xu, Y, Ma, Q, Lin, Z, Schlame, M et al.. AAV Gene Therapy Prevents and Reverses Heart Failure in a Murine Knockout Model of Barth Syndrome. Circ Res. 2020;126 (8):1024-1039. doi: 10.1161/CIRCRESAHA.119.315956. PubMed PMID:32146862 PubMed Central PMC7233109.
  12. Chen, J, Ma, Q, King, JS, Sun, Y, Xu, B, Zhang, X et al.. aYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model. Life Sci Alliance. 2020;3 (1):. doi: 10.26508/lsa.201900424. PubMed PMID:31843959 PubMed Central PMC6918510.
  13. Yu, W, Ma, X, Xu, J, Heumüller, AW, Fei, Z, Feng, X et al.. VGLL4 plays a critical role in heart valve development and homeostasis. PLoS Genet. 2019;15 (2):e1007977. doi: 10.1371/journal.pgen.1007977. PubMed PMID:30789911 PubMed Central PMC6400400.
  14. Zhang, D, Li, Y, Heims-Waldron, D, Bezzerides, V, Guatimosim, S, Guo, Y et al.. Mitochondrial Cardiomyopathy Caused by Elevated Reactive Oxygen Species and Impaired Cardiomyocyte Proliferation. Circ Res. 2018;122 (1):74-87. doi: 10.1161/CIRCRESAHA.117.311349. PubMed PMID:29021295 PubMed Central PMC5756124.
  15. Hu, Y, Shin, DJ, Pan, H, Lin, Z, Dreyfuss, JM, Camargo, FD et al.. YAP suppresses gluconeogenic gene expression through PGC1α. Hepatology. 2017;66 (6):2029-2041. doi: 10.1002/hep.29373. PubMed PMID:28714135 PubMed Central PMC6082140.
  16. Sun, Y, Lin, Z, Liu, CH, Gong, Y, Liegl, R, Fredrick, TW et al.. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J Exp Med. 2017;214 (6):1753-1767. doi: 10.1084/jem.20161645. PubMed PMID:28465464 PubMed Central PMC5461000.
  17. Ai, S, Peng, Y, Li, C, Gu, F, Yu, X, Yue, Y et al.. EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent. Elife. 2017;6 :. doi: 10.7554/eLife.24570. PubMed PMID:28394251 PubMed Central PMC5400508.
  18. Zhou, P, Gu, F, Zhang, L, Akerberg, BN, Ma, Q, Li, K et al.. Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq. Elife. 2017;6 :. doi: 10.7554/eLife.22039. PubMed PMID:28121289 PubMed Central PMC5295818.
  19. Lin, Z, Guo, H, Cao, Y, Zohrabian, S, Zhou, P, Ma, Q et al.. Acetylation of VGLL4 Regulates Hippo-YAP Signaling and Postnatal Cardiac Growth. Dev Cell. 2016;39 (4):466-479. doi: 10.1016/j.devcel.2016.09.005. PubMed PMID:27720608 PubMed Central PMC5121000.
  20. Yu, W, Huang, X, Tian, X, Zhang, H, He, L, Wang, Y et al.. GATA4 regulates Fgf16 to promote heart repair after injury. Development. 2016;143 (6):936-49. doi: 10.1242/dev.130971. PubMed PMID:26893347 .
  21. Huang, ZP, Kataoka, M, Chen, J, Wu, G, Ding, J, Nie, M et al.. Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis. J Clin Invest. 2015;125 (11):4122-34. doi: 10.1172/JCI82423. PubMed PMID:26436652 PubMed Central PMC4639982.
  22. Sun, Y, Ju, M, Lin, Z, Fredrick, TW, Evans, LP, Tian, KT et al.. SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth. Sci Signal. 2015;8 (395):ra94. doi: 10.1126/scisignal.aaa8695. PubMed PMID:26396267 PubMed Central PMC4659437.
  23. Ding, J, Chen, J, Wang, Y, Kataoka, M, Ma, L, Zhou, P et al.. Trbp regulates heart function through microRNA-mediated Sox6 repression. Nat Genet. 2015;47 (7):776-83. doi: 10.1038/ng.3324. PubMed PMID:26029872 PubMed Central PMC4485565.
  24. Prendiville, TW, Guo, H, Lin, Z, Zhou, P, Stevens, SM, He, A et al.. Novel Roles of GATA4/6 in the Postnatal Heart Identified through Temporally Controlled, Cardiomyocyte-Specific Gene Inactivation by Adeno-Associated Virus Delivery of Cre Recombinase. PLoS One. 2015;10 (5):e0128105. doi: 10.1371/journal.pone.0128105. PubMed PMID:26023924 PubMed Central PMC4449121.
  25. Lin, Z, Pu, WT. Releasing YAP from an α-catenin trap increases cardiomyocyte proliferation. Circ Res. 2015;116 (1):9-11. doi: 10.1161/CIRCRESAHA.114.305496. PubMed PMID:25552687 PubMed Central PMC4283556.
  26. Lin, Z, Zhou, P, von Gise, A, Gu, F, Ma, Q, Chen, J et al.. Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival. Circ Res. 2015;116 (1):35-45. doi: 10.1161/CIRCRESAHA.115.304457. PubMed PMID:25249570 PubMed Central PMC4282610.
  27. Prendiville, TW, Ma, Q, Lin, Z, Zhou, P, He, A, Pu, WT et al.. Ultrasound-guided transthoracic intramyocardial injection in mice. J Vis Exp. 2014; (90):e51566. doi: 10.3791/51566. PubMed PMID:25146757 PubMed Central PMC4267063.
  28. Lin, Z, Pu, WT. Strategies for cardiac regeneration and repair. Sci Transl Med. 2014;6 (239):239rv1. doi: 10.1126/scitranslmed.3006681. PubMed PMID:24898748 PubMed Central PMC4280908.
  29. Lin, Z, Pu, WT. Harnessing Hippo in the heart: Hippo/Yap signaling and applications to heart regeneration and rejuvenation. Stem Cell Res. 2014;13 (3 Pt B):571-81. doi: 10.1016/j.scr.2014.04.010. PubMed PMID:24881775 PubMed Central PMC4223001.
  30. Lin, Z, von Gise, A, Zhou, P, Gu, F, Ma, Q, Jiang, J et al.. Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model. Circ Res. 2014;115 (3):354-63. doi: 10.1161/CIRCRESAHA.115.303632. PubMed PMID:24833660 PubMed Central PMC4104149.
  31. Chen, J, Huang, ZP, Seok, HY, Ding, J, Kataoka, M, Zhang, Z et al.. mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ Res. 2013;112 (12):1557-66. doi: 10.1161/CIRCRESAHA.112.300658. PubMed PMID:23575307 PubMed Central PMC3756475.
  32. von Gise, A, Lin, Z, Schlegelmilch, K, Honor, LB, Pan, GM, Buck, JN et al.. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc Natl Acad Sci U S A. 2012;109 (7):2394-9. doi: 10.1073/pnas.1116136109. PubMed PMID:22308401 PubMed Central PMC3289361.
  33. Lin, Z, Murtaza, I, Wang, K, Jiao, J, Gao, J, Li, PF et al.. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc Natl Acad Sci U S A. 2009;106 (29):12103-8. doi: 10.1073/pnas.0811371106. PubMed PMID:19574461 PubMed Central PMC2715539.
  34. Lin, Z, Yin, K, Zhu, D, Chen, Z, Gu, H, Qu, LJ et al.. AtCDC5 regulates the G2 to M transition of the cell cycle and is critical for the function of Arabidopsis shoot apical meristem. Cell Res. 2007;17 (9):815-28. doi: 10.1038/cr.2007.71. PubMed PMID:17768399 .
  35. Lin, Z, Yin, K, Wang, X, Liu, M, Chen, Z, Gu, H et al.. Virus induced gene silencing of AtCDC5 results in accelerated cell death in Arabidopsis leaves. Plant Physiol Biochem. 2007;45 (1):87-94. doi: 10.1016/j.plaphy.2006.12.003. PubMed PMID:17298883 .
  36. Yanhui, C, Xiaoyuan, Y, Kun, H, Meihua, L, Jigang, L, Zhaofeng, G et al.. The MYB transcription factor superfamily of Arabidopsis: expression analysis and phylogenetic comparison with the rice MYB family. Plant Mol Biol. 2006;60 (1):107-24. doi: 10.1007/s11103-005-2910-y. PubMed PMID:16463103 .
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Chase Kessinger, Ph.D.

Chase Kessinger, Ph.D.

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