Cardiovascluar Stem Cell Biology

Research Interests

  • 1. Environmental Cardiology

    Induced pluripotent stem cells (iPSCs) are a powerful model system for medical discovery and translational research. At present, most studies have focused on the potential for iPSCs for regenerative medicine, drug discovery, and disease modeling. However, iPSCs are also a powerful model system to investigate the effects of environment risk factors such as e-cigarettes, marijuana, air pollution, and opioids on the cardiovascular system.

  • 2. Diabetes and Cardiovascular Disease

    Insulin resistance is central to the development of type 2 diabetes (T2D) and presents a major risk factor for cardiovascular disease. Insulin resistance is difficult to diagnose prior to the onset of T2D and is often underdiagnosed with the prevalence of insulin resistance estimated to be three times greater than T2D. The causes of insulin resistance and how it impacts the vascular system are not fully understood. Therefore, there is a need for early diagnostics for insulin resistance and potential therapeutic targets.

  • 3. Exosomes and Biomarkers

    Cells can communicate with each other via small vesicle packets called exosomes. Exosomes contain nucleic acid, protein , and lipids. The collection of molecules released by secreted exosomes can influence nearby cells’ behavior, function, development, and even identity. Exosomal content might be implicated in the mechanisms of cardiomyopathy and could serve as biomarkers or targets for drug discovery.

  • Links

    PubMed

    Google Scholar

    ORCID

    Robarts Research Institute

    Schulich Cardiology

    Western University Physiology and Pharmacology

    AHA23 Presidential Address: Dr Joseph Wu

  • Publications

    1. Wei TT, Chandy M, Nishiga M, Zhang A, Kumar KK, Thomas D, Manhas A, Rhee S, Justesen JM, Chen IY, Wo HT, Khanamiri S, Yang JY, Seidl FJ, Burns NZ, Liu C, Sayed N, Shie JJ, Yeh CF, Yang KC, Lau E, Lynch KL, Rivas M, Kobilka BK, Wu JC. Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation. Cell. 2022 May 12;185(10):1676-1693.e23. doi: 10.1016/j.cell.2022.04.005. Epub 2022 Apr 29. PubMed PMID: 35489334.

    2. Veitch*, S, Njock*, M-S, Chandy*, M., Siraj, A.; Chi, L.; Mak, HQ; Yu, K.; Rathnakumar, K.; Romero, C.A.P.; Chen, Z.; Alibhai, F.J.; Gustafson, D.; Raju, S.; Wu, R.; Khat, D.; Wang, Y.; Caballero, A.; Meagher, P.; Lau, E.; Pepic, L.; Cheng, H.S.; Galant, N.J.; Howe, K.L.; Li, R-k; Connelly, K.A.; Husain, M.; Delgado-Olguin, P.; Fish, J. MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes. Cardiovasc Diabetol. 2022 Feb 24;21(1):31.doi:10.1186/s12933-022-01458-z.

    3. Rhee*, S., Paik, D. T., Yang, J. Y., Nagelberg, D., Williams, I., Tian, L., Roth, R., Chandy, M., Ban, J., Belbachir,N., Kim, W., Zhang, H., Phansalkar, R., Wong, K.M., King, D.A., Valdez, C., Winn, V., Morrison, A.J., Wu , J.C., Red-Horse, K. Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction. Eur Heart J. 2021 Jul 19;ehab298.doi: 10.1093/eurheartj/ehab298.

    4. Chour T, Tian L, Lau E, Thomas D, Itzhaki I, Malak O, Zhang JZ, Qin X, Wardak M, Liu Y, Chandy M, Black KE, Lam MP, Neofytou E, Wu JC. Method for selective ablation of undifferentiated human pluripotent stem cell populations for cell-based therapies. JCI Insight. 2021 Apr 8;6(7):142000. doi: 10.1172/jci.insight.142000. PMID: 33830086.

    5. Chandy*, M, Rhee*, J, Ozen*, M, Williams, D, Pepic, L, Lui, C, Zhang, H, Malisa, J, Lau*, E, Demirci*, U, Wu*, JC. Atlas of Exosomal microRNAs Secreted From Human iPSC-Derived Cardiac Cell Types. Circulation. 2020;142:1794–17968.

    6. M Chandy, M Ishida, O El-Mouranyi, EA Shikatani, C Park, T Alfrooze, P Marsden and M Husain. c-Myb and microRNA 143/145 Gene Expression in Vascular Smooth Muscle. PLoS One. 2018 Aug 31;13(8):e0202778.

    7. Steinbach SK, Yau TM, Ouzounian M, Abdel-Qadir H, Chandy M, Waddell T, Husain M. Skin-derived precursors from human subjects with Type 2 diabetes yield dysfunctional vascular smooth muscle cells. Clin Sci (Lond). 2017 Jul 5;131(15):1801- 1814. doi: 10.1042/CS20170239.

    8. Shikatani EA, Chandy M, Besla R, Li CC, Momen A, El-Mounayri O, Robbins CS,Husain M. c-Myb Regulates Proliferation and Differentiation of Adventitial Sca1+Vascular Smooth Muscle Cell Progenitors by Transactivation of Myocardin. Arterioscler Thromb Vasc Biol. 2016 May 12. pii: ATVBAHA.115.307116

    9. Almehmadi, F, Chandy, M, Connelly, K and Edwards, J. Delayed Tamponade after Traumatic Wound with Left Ventricular Compression. Case Reports in Cardiology vol. 2016, Article ID 2154748, 3 pages, 2016. doi:10.1155/2016/2154748.

    10. Gandhi S, Litt D, Chandy M et al. Successful rapid intravenous desensitization for radioiodine contrast allergy in a patient requiring urgent coronary angiography. J Allergy Clin Immunol Pract. 2014 Jan-Feb;2(1):101-2

    11. Gutierrez JL, Chandy M, Carrozza MJ, Workman JL. Activation domains drive nucleosome eviction by SWI/SNF. EMBO J. 2007 Feb 7;26(3):730-40.

    12. Chandy M, Gutierrez JL, Prochasson P, Workman JL. SWI/SNF displaces SAGAacetylated nucleosomes. Eukaryot Cell. 2006 Oct;5(10):1738-47.

    13. Robert F, Pokholok DK, Hannett NM, Rinaldi NJ, Chandy M, Rolfe A, Workman JL, Gifford DK, Young RA. Global Position and Recruitment of HATs and HDACs in the Yeast Genome. Mol Cell 16(2):199-209

    14. Jeronimo C, Langelier MF, Zeghouf M, Cojocaru M, Bergeron D, Baali D, Forget D, Mnaimneh S, Davierwala AP, Pootoolal J, Chandy M, Canadien V, Beattie BK, Richards DP, Workman JL, Hughes TR, Greenblatt J, Coulombe B. RPAP1, a novel human RNA polymerase II-associated protein affinity purified with recombinant wild-type and mutated polymerase subunits. Mol Cell Biol (16):7043-58

    15. Hassan, AH, Prochasson, P., Neely, KE, Galasinski, SC, Chandy, M, Carrozza ,MJ, Workman, JL. Function and selectivity of bromodomains in anchoring chromatinmodifying complexes to promoter nucleosomes. Cell. 2002 Nov 1;111(3):369-79.

    16. Liu, D., Chandy, M., Lee, S.K., Le Dréan, Y., Ando, H., Xiong, F., Lee J.W., andHew, C.L. A Zebrafish Ftz-F1 (Fushi Tarazu Factor 1) Homolog RequiresMultiple Subdomains in the D and E Regions for Its Transcriptional Activity. Journal of Biological Chemistry. Vol. 275, No. 22: 16758-16766.

  • Reviews

    1. Bae, HR, Aguilera, J, Smith, EM, Chandy, M, Nadeau, KC, Wu, JC, Paik, DT. Adverse effects of air pollution-derived fine particulate matter on cardiovascular homeostasis and disease. (in revision)

    2. Paik, DT, Chandy, M, Wu, JC. Patient-Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics. Pharm Rev. 2020; 72 (1): 320–42

    3. Chandy, M. A tangled tale of microRNA and cardiac fibrosis. Clin Sci (Lond). (2019) 133 (21): 2217-2220.

    4. Chandy M, Wu JC. Induced pluripotent stem cells in cardiovascular precision medicine. HealthManagement.org The Journal 2017;17(2):168-9.

    5. Pattenden SG, Chandy M, Gutierrez JL, Workman JL. Chromatin dynamics rule the genome. Genome Biol. 2005;6(11):355.

  • Book Chapter

    1. Chandy, M and Wu, JC. Molecular Imaging of Stem Cells in Myocardial Infarction. Molecular Imaging: Principles and Practice. Edited by Brian D. Ross and Sanjiv S. Gambhir.

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