Zhenwu Zhuang, MD, MS
Research & Publications
Dr. Zhuang’s research interests include multi-modality imaging in the cardiovascular system, the neurovascular system, and tumors. Currently, his research is focusing on developing micro-imaging approaches (microCT and micro-SET) for the assessment of angiogenesis, arteriogenesis, and vascular remolding. Because of his interventional radiologist background, he is also interested in translational research to develop strategies for local gene or cellular therapies and evaluate the therapeutic efficacy using noninvasive imaging approaches for coronary microvascular disease, ischemic stroke, and cardiac arrest.
Specialized Terms: Angiogenesis; Arteriogenesis; Vascular/Cardiac Remolding; Vascular Integrity; MicroCT; Micro-SPECT; MR; Molecular Imaging; Interventional Cardiology/Radiology; Gene Therapy; Cell Therapy; Cardiac Repair; Phenotype; Cardiovascular Development; Lung; Tumor; Nanoparticle; Thrombosis; Fibrinolysis; Coronary microvascular disease; Factor XIII; cardiac arrest; ischemic stroke, and Alzheimer' disease (AD)
Extensive Research Description
Novel molecular imaging for early detection of microthrombi in the microvasculature. The exact mechanism and importance of coronary microvascular disease (MVD), under conditions of ischemic injury, are still unclear. Based on two notions: 1) endothelial cells can be damaged and platelets can be activated by photosensitizers irradiated by a specific wavelength of the laser in the heart of a mouse; 2) coagulation factor XIII is required for the impairment of microvascular function progress, we are establishing a novel animal model of MVD and applying non-invasive imaging strategy to dynamically monitor cross-linking thrombi formation and to document subsequent cardiac function in rodents following ischemic injury.
Molecular Imaging of Histone Deacetylase 6 Activity as an Epigenetic Biomarker in Ischemic Stroke. Cerebral ischemic injury is thought to result from a cascade of events ranging from energy depletion, excitotoxicity, oxidative stress, neuroinflammation, and programmed cell death to neuron survival and growth. Despite advances in genetic mechanisms, tissue plasminogen activator (tPA) infusion, or mechanical thrombectomy, the clinical outcome of ischemic stroke remains disappointing. Different from genetic regulation, epigenetic dysregulation, which does not change the DNA sequence, could be a pathological hallmark of ischemic stroke, which in turn triggers multiple events at different stages after ischemic insult. HDAC6 is a unique histone deacetylase (HDACs) subtype and takes part in multiple pathological events of ischemic stroke. In preliminary studies, we found that levels of HDAC6 antigen and protein expression had increased in the ischemic region in the early stages of stroke in mice. We also found that an HDAC6 inhibitor, ACY-775, was effective in mitigating infarct size and improving neurological recovery in mice. Based upon these initial results, we hypothesize that HDAC6 is a specific biomarker for the severity of the cerebral ischemic injury and that suppression of HDAC6 activity can rescue neurons from hypoxic damage by an ischemic attack.
PET imaging of Pre-synaptic Vesicle Density for cognitive dysfunction in Cardiac Arrest.
Sudden cardiac arrest (CA) accounts for 50% of all cardiovascular deaths in the US. Despite advances in post-resuscitation care and management, only 10.8% of adult out-of-hospital CA (OHCA) victims survive hospital discharge, and up to 50% of survived patients exhibit cognitive deficits (learning/memory disabilities, executive function). It is well-accepted that cognitive dysfunction is associated with synaptic dysfunction and the inability to induce physiological long-term potentiation (LTP) in the CA1 region of the hippocampus after global ischemia. These deficits suggest that synaptic dysfunction in specific regions (such as the hippocampus or cortex) might be responsible for post-CA brain injury (PCABI). In addition, levels of impairment or recovery of neurologic function govern long-term outcomes after CA, and prediction of the potential for recovery is a heavy burden for physicians and patients’ families. A sensitive and reliable in vivo approach to assess the loss and partial restoration of synaptic function or density, if it can provide early information on the severity of synaptic dysfunction, monitor the neuron recovery, and predict the outcome.
Cardiology; Coronary Disease; Fibrinolysis; Microscopy; Phenotype; Thrombosis; Genetic Therapy; Radiology, Interventional; Nanoparticles
- Elevated follicular helper T Cells and expression of IL-21 in thyroid tissues are involved in the pathogenesis of Graves’ diseaseZhang J, Ren M, Zeng H, Guo Y, Zhuang Z, Feng Z, Yan H, Xu M, Liang W, Yang C, Cheng H, Ding H, Yan L. Elevated follicular helper T Cells and expression of IL-21 in thyroid tissues are involved in the pathogenesis of Graves’ disease Immunologic Research 2015, 62: 163-174. PMID: 25894310, DOI: 10.1007/s12026-015-8647-z.
- Endothelial Cell–Dependent Regulation of ArteriogenesisMoraes F, Paye J, Gabhann F, Zhuang ZW, Zhang J, Lanahan AA, Simons M. Endothelial Cell–Dependent Regulation of Arteriogenesis Circulation Research 2013, 113: 1076-1086. PMID: 23897694, PMCID: PMC3865810, DOI: 10.1161/circresaha.113.301340.
- NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growthJaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth Journal Of Clinical Investigation 2013, 123: 1718-1731. PMID: 23454748, PMCID: PMC3613910, DOI: 10.1172/jci65112.
- Vascular adaptation to a dysfunctional endothelium as a consequence of Shb deficiencyChristoffersson G, Zang G, Zhuang ZW, Vågesjö E, Simons M, Phillipson M, Welsh M. Vascular adaptation to a dysfunctional endothelium as a consequence of Shb deficiency Angiogenesis 2012, 15: 469-480. PMID: 22562363, PMCID: PMC4059510, DOI: 10.1007/s10456-012-9275-z.
- Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesisTakeda Y, Costa S, Delamarre E, Roncal C, Leite de Oliveira R, Squadrito ML, Finisguerra V, Deschoemaeker S, Bruyère F, Wenes M, Hamm A, Serneels J, Magat J, Bhattacharyya T, Anisimov A, Jordan BF, Alitalo K, Maxwell P, Gallez B, Zhuang ZW, Saito Y, Simons M, De Palma M, Mazzone M. Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis Nature 2011, 479: 122-126. PMID: 21983962, PMCID: PMC4659699, DOI: 10.1038/nature10507.
- Development and Application of a Multimodal Contrast Agent for SPECT/CT Hybrid ImagingCriscione JM, Dobrucki LW, Zhuang ZW, Papademetris X, Simons M, Sinusas AJ, Fahmy TM. Development and Application of a Multimodal Contrast Agent for SPECT/CT Hybrid Imaging Bioconjugate Chemistry 2011, 22: 1784-1792. PMID: 21851119, PMCID: PMC3204385, DOI: 10.1021/bc200162r.
- FGF-dependent regulation of VEGF receptor 2 expression in miceMurakami M, Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, Black BL, Simons M. FGF-dependent regulation of VEGF receptor 2 expression in mice Journal Of Clinical Investigation 2011, 121: 2668-2678. PMID: 21633168, PMCID: PMC3223828, DOI: 10.1172/jci44762.
- Challenging the Surgical Rodent Hindlimb Ischemia Model with the Miniinterventional TechniqueZhuang ZW, Shi J, Rhodes JM, Tsapakos MJ, Simons M. Challenging the Surgical Rodent Hindlimb Ischemia Model with the Miniinterventional Technique Journal Of Vascular And Interventional Radiology 2011, 22: 1437-1446. PMID: 21459613, PMCID: PMC3367666, DOI: 10.1016/j.jvir.2010.12.039.
- Tissue-Engineered Lungs for in Vivo ImplantationPetersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE. Tissue-Engineered Lungs for in Vivo Implantation Science 2010, 329: 538-541. PMID: 20576850, PMCID: PMC3640463, DOI: 10.1126/science.1189345.
- VEGF Receptor 2 Endocytic Trafficking Regulates Arterial MorphogenesisLanahan AA, Hermans K, Claes F, Kerley-Hamilton JS, Zhuang ZW, Giordano FJ, Carmeliet P, Simons M. VEGF Receptor 2 Endocytic Trafficking Regulates Arterial Morphogenesis Developmental Cell 2010, 18: 713-724. PMID: 20434959, PMCID: PMC2875289, DOI: 10.1016/j.devcel.2010.02.016.
- Aging‐induced collateral impairment: role of arterial rarefaction, decreased eNOS expression/signaling, and increased susceptibility of endothelial cells to apoptosisEpstein S, Wang J, Peng X, Zhuang Z, Simons M, Xue Z, Burnett M. Aging‐induced collateral impairment: role of arterial rarefaction, decreased eNOS expression/signaling, and increased susceptibility of endothelial cells to apoptosis The FASEB Journal 2010, 24: 294.3-294.3. DOI: 10.1096/fasebj.24.1_supplement.294.3.
- ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafishRen B, Deng Y, Mukhopadhyay A, Lanahan AA, Zhuang ZW, Moodie KL, Mulligan-Kehoe MJ, Byzova TV, Peterson RT, Simons M. ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish Journal Of Clinical Investigation 2010, 120: 1217-1228. PMID: 20237411, PMCID: PMC2846043, DOI: 10.1172/jci39837.
- FGF mediates maintenance of vascular integrity in a Csk dependent mannerMurakami M, Zhuang Z, Moodie K, Stan R, Simons M. FGF mediates maintenance of vascular integrity in a Csk dependent manner The FASEB Journal 2008, 22: 329.5-329.5. DOI: 10.1096/fasebj.22.1_supplement.329.5.
- Arteriogenesis: Noninvasive Quantification with Multi–Detector Row CT Angiography and Three-dimensional Volume Rendering in RodentsZhuang ZW, Gao L, Murakami M, Pearlman JD, Sackett TJ, Simons M, de Muinck ED. Arteriogenesis: Noninvasive Quantification with Multi–Detector Row CT Angiography and Three-dimensional Volume Rendering in Rodents Radiology 2006, 240: 698-707. PMID: 16926325, DOI: 10.1148/radiol.2403050976.
- An interactive 3D visualization and manipulation tool for effective assessment of angiogenesis and arteriogenesis using computed tomographic angiographyShen L, Gao L, Zhuang Z, DeMuinck E, Huang H, Makedon F, Pearlman J. An interactive 3D visualization and manipulation tool for effective assessment of angiogenesis and arteriogenesis using computed tomographic angiography Proceedings Of SPIE 2005, 5744: 848-858. DOI: 10.1117/12.596138.
- 1121-52 Inhibition of in-stent restenosis in porcine coronary arteries by copper chelationMandinov L, Moodie K, Mandinova A, Zhuang Z, Maciag T, Simons M, de Muinck E. 1121-52 Inhibition of in-stent restenosis in porcine coronary arteries by copper chelation Journal Of The American College Of Cardiology 2004, 43: a78. DOI: 10.1016/s0735-1097(04)90323-3.
- Adventitial Angiogenesis Drives Neointima FormationKhurana R, Martin J, Zachary I, Zhuang Z, De Muinck E, Simons M, Bhardwaj S, Yla-Herttuala S, Ferrara N. Adventitial Angiogenesis Drives Neointima Formation Clinical Science 2004, 106: 1p-1p. DOI: 10.1042/cs106001p.