My research interests focus on the molecular and genetic basis underlying cardiovascular diseases (CVD). The ultimate goal of the study is to provide helpful knowledge when developing new treatments for CVD. I was leading two main research projects, including:
1. The role of gut microbiota and their metabolites in the pathogenesis of obstructive sleep apnea (OSA)-induced atherosclerosis.
Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive episodes of complete or partial upper airway obstruction, which lead to intermittent hypoxia and hypercapnia (IHC) as well as sleep fragmentation (SF). Clinical data revealed that OSA increases atherosclerosis risk. We have demonstrated in ApoE-/- and Ldlr-/- mice (two most commonly used atherosclerosis animal models), that (1) IHC accelerated the development of atherosclerosis, (2) IHC changed the gut microbiota ecology and associated metabolites, (3) DMB, a microbial TMA lyase inhibitor, significantly attenuated IHC-induced atherosclerosis, (4) IHC had greater impact on the formation of atherosclerosis than SF or high fat diet (HFD), and (5) Germ free ApoE-/- mice had reduced atherosclerotic lesion as compared to conventionally-reared ApoE-/- mice.
Selected Publications:
- D. Zhou, J. Xue, Y. Miyamoto, O. Poulsen, L. Eckmann and G.G. Haddad (2021). "Microbiota Modulates Cardiac Transcriptional Responses to Intermittent Hypoxia and Hypercapnia". Frontiers in Physiology. 12:680275.
- J. Xue*, C. Allaband*, D. Zhou, O. Poulsen, C. Martino, L. Jiang, A. Tripathi, E. Elijah, P.C. Dorrestein, R. Knight, A. Zarrinpar and G.G. Haddad (2021). "Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome". Frontiers in Physiology. 12:663950. * J. Xue and C. Allaband contributed equally as first authors.
- A. Tripathi, Z.Z. Xu, J. Xue, O. Poulsen, A. Gonzalez, G. Humphrey, M. Meehan, A.V. Melnik, G. Ackermann, D. Zhou, A. Malhotra, G.G. Haddad, P.C. Dorrestein and R. Knight (2019). "Intermittent Hypoxia and Hypercapnia Reproducibly Change the Gut Microbiome and Metabolome across Rodent Model Systems". mSystems. 4(2). pii: e00058-19.
- A. Tripathi, A.V. Melnik, J. Xue, O. Poulsen, M.J. Meehan, G. Humphrey, L. Jiang, G. Ackermann, D. McDonald, D. Zhou, R. Knight, P.C. Dorrestein and G.G. Haddad (2018). "Intermittent Hypoxia and Hypercapnia, a Hallmark of Obstructive Sleep Apnea, Alters the Gut Microbiome and Metabolome". mSystems. 3(3). pii: e00020-18.
- J. Xue, D. Zhou, O. Poulsen, T. Imamura, Y. Hsiao, T.H. Smith, A. Malhotra, P. Dorrestein, R. Knight and G.G. Haddad (2017). "Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, partially via Trimethylamine-Oxide". American Journal of Respiratory Cell and Molecular Biology. 57(5):581-588.
2. Regulatory mechanism in NHE1 mediated cardiac injury.
Hypoxic injury often occurs in many clinical conditions, such as myocardial infarction and ischemic stroke. My work and others have demonstrated that NHE1 is a key player in hypoxic injury. Our studies revealed that (1) NHE1 was regulated by intermittent or chronic hypoxia, (2) NHE1 induced gene expression changes and had pathological consequences in the heart and brain. We have shown that heart specific NHE1 transgenic mice develop cardiac hypertrophy, fibrosis and cardiac dysfunction. We further identified SPP1 and its associated signaling as well as certain miRNA-mRNA regulated networks are important for NHE1-mediated cardiac injury.
Selected Publications:
- J. Xue, D. Zhou, I. Hartley, O. Poulsen and G.G. Haddad (2018). "Exploring miRNA-mRNA Regulatory Network in Cardiac Pathology in Na+/H+ Exchanger Isoform 1 Transgenic Mice". Physiological Genomics. 50(10):846-861.
- J. Xue, F. Mraiche, D. Zhou, M. Karmazyn, T. Oka, L. Fliegel and G.G. Haddad (2010). "Elevated Myocardial Na+/H+ Exchanger Isoform 1 Activity Elicits Gene Expression that Leads to Cardiac Hypertrophy". Physiological Genomics. 42(3):374-83.
- J. Xue, D. Zhou, H. Yao and G.G. Haddad (2008). "Role of Transporters and Ion Channels in Neuronal Injury under Hypoxia". American Journal of Physiology Regulatory, Integrative and Comparative Physiology. 294(2):R451-7.
- J. Xue, D. Zhou, H. Yao, O. Gavrialov, M. McConnell, B.D. Gelb and G.G. Haddad (2007). "Novel Functional Interaction between Na+/H+ Exchanger 1 and Tyrosine Phosphatase SHP-2". American Journal of Physiology Regulatory, Integrative and Comparative Physiology. 292(6):R2406-16.
- J. Xue, R.M. Douglas, D. Zhou, J.Y. Lim and G.G. Haddad (2003). "Expression of Sodium-Hydrogen Exchangers and Bicarbonate-Dependent Transporters in the NHE1 Null Mutant Mouse Brain". Neuroscience, 122(1):37-46.
- R.M. Douglas, J. Xue, J.Y. Chen, C.G. Haddad, S.L. Alper and G.G. Haddad (2003). "Chronic Intermittent Hypoxia Decreases the Expression of Sodium-Hydrogen Exchangers and Bicarbonate-dependent Transporters in the Mouse Central Nervous System". Journal of Applied Physiology, 95 (1): 292-299.