The Jhun laboratory aims to identify the molecular mechanisms involved in the development of cardiovascular diseases. We are particularly interested in mitochondrial signaling pathways that control mitochondrial fission, fusion, and ion transport during physiological conditions, and how alterations in these processes influence mitochondrial and cellular function under pathological conditions. To this end, we utilize a wide range of techniques from genetic, biochemical, molecular/cell biological, and physiological approaches to in vivo animal models of cardiovascular diseases. Elucidation of these regulatory mechanisms will facilitate the design of novel therapeutic strategies for the management of cardiovascular diseases.
- Current Lab Projects
- Lab Members
- Selected Publications
Current Lab Projects
"Role of PKD in right ventricular dysfunction during pulmonary arterial hypertension"
Pulmonary arterial hypertension (PAH) is associated with a progressive increase in vascular remodeling and right ventricular (RV) failure. Despite advances in the clinical management and the availability of vasodilator therapies, PAH remains associated with high mortality. RV failure is the main cause of death in PAH and the maintenance of RV function in PAH is associated with improved patient survival. However, there is no available therapy that specifically targets RV dysfunction. Therefore, new therapeutic approaches are urgently needed to specifically target RV failure in PAH to be used in conjunction with conventional treatment for pulmonary vascular resistance.
Our preliminary studies suggest that PKD-dependent mitochondrial signaling may serve as a critical mediator for RV myocyte apoptosis and RV fibroblast proliferation/differentiation, which contributes to the progression of RV failure in PAH. We are currently investigating the detailed molecular mechanisms of how PKD-mediated mitochondrial signaling induces different cellular responses in RV myocytes and RV fibroblasts. This study will provide new insights into the molecular mechanisms underlying PAH-induced RV failure. Moreover, the outcome of this project will lead to the design of a novel strategy for management of RV failure in the setting of PAH. (Partially supported by American Heart Association Career Development Award #18CDA34110091, PI: Jhun).
"Regulation and Function of Mitochondrial Ion Channels/Transporters in the Cardiovascular System"
In collaboration with internal and external investigators, the Jhun laboratory is investigating the regulatory mechanisms and functional roles of various ion channels and transporters in cell survival and death in the cardiovascular system. These include mitochondrial calcium uniporter (NIH/NHLBI R01HL136757, PI: O-Uchi & Co-I: Jhun and University of Minnesota IEM Group Program Grant, MPIs: Talkachova, O-Uchi, Dudley & Co-I: Jhun) and calcium-activated chloride channel Anoctamin 1 (NIH/NHLBI R01HL148727 PI: Choudhary & Co-I: Jhun).
Principal Investigator: Bong Sook Jhun, PhD, FCVS
Assistant Professor of Medicine
Lillehei Heart Institute
Department of Medicine
University of Minnesota
Xiaoxu Zhou, MD, PhD
Assistant Professor of Medicine
Michael W. Cypress, PhD
Lab Manager for Jhun and O-Uchi labs
Bridget Nieto, BS
Animal Research Specialist for Jhun and O-Uchi labs
Undergraduate Research Asociate
Neeta Adhikari, PhD
Jordan Schlichting, BS
Research Technician for Jhun and O-Uchi labs
Full list of publications at Experts@Minnesota
1. Adaniya SM, O-Uchi J, Cypress MW, Kusakari Y, Jhun BS#: Posttranslational Modifications of Mitochondrial Fission and Fusion Proteins in Cardiac Physiology and Pathophysiology. Am J Physiol Cell Physiol. 2019, 316(5): C583-C604. PMID: 30758993 (#Corresponding author)
2. Jhun BS#, O-Uchi J#, Adaniya SM, Cypress MW, Yoon Y. Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology. Antioxidants. 2018, 7(12): E195, PMID: 30567380 (#Corresponding author)
3. Jhun BS#, O-Uchi J#, Adaniya SM, Mancini TJ, Cao JL, King ME, Landi AK, Ma H, Shin M, Yang D, Xu X, Yoon Y, Choudhary G, Clements RT, Mende U, Sheu SS#: Protein kinase D activation induces mitochondrial fragmentation and dysfunction in cardiomyocytes. J. Physiol. 2018, 596(5):827-855. PMCID: PMC5830422 (#Corresponding author)
4. Jhun BS*, Mishra J*, Hurst S, O-Uchi J, Csordás G, Sheu SS. The Mitochondrial Ca2+ uniporter: Structure, Function and Pharmacology. Handb Exp Pharmacol. 2017, 240:129-156. PMCID: PMC5554456 (*Equal contribution)
5. Jhun BS*, Mishra J, Monaco S, Fu D, Jiang W, Sheu SS, O-Uchi J: The mitochondrial Ca2+ uniporter: Regulation by auxiliary subunits and signal transduction pathways. Am J Physiol Cell Physiol. 2016, 311(1):C67-80. PMCID: PMC4967134. (*Equal contribution)
6. Jhun BS*, O-Uchi Jin*, Xu S, Hurst S, Raffaello A, Liu X, Yi B, Zhang H, Gross P, Mishra J, Ainbinder A, Kettlewell S, Smith GL, Dirksen RT, Wang W, Rizzuto R, Sheu SS: Adrenergic signaling regulates mitochondrial Ca2+ uptake through Pyk2-dependent tyrosine phosphorylation of the mitochondrial Ca2+ uniporter. Antioxid Redox Signal. 2014, 21(6):863-79. PMCID: PMC4116095 (*Equal contribution)
7. O-Uchi J, Jhun BS, Hurst S, Bisetto S, Gross P, Chen M, Kettlewell S, Park J, Oyamada H, Smith GL, Murayama T, Sheu SS: Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts. Am J Physiol Heart Circ Physiol. 2013, 305(12):H1736-51. PMCID: PMC3882548
8. Jhun BS, Lee H, Jin ZG, Yoon Y: Glucose stimulation induces dynamic change of mitochondrial morphology to promote insulin secretion in the insulinoma cell line INS-1E. PLoS One. 2013, 8(4):e60810. PMCID: PMC3614983
9. Galloway CA, Lee H, Nejjar S, Jhun BS, Yu T, Hsu W, Yoon Y: Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress in mice. Diabetes. 2012, 61(8): 2093-2104. PMCID: PMC3402299
10. Jhun BS*, O-Uchi Jin*, Wang W, Ha CH, Zhao J, Kim JY, Wong C, Dirksen RT, Lopes CM, Jin ZG: Adrenergic signaling controls RGK-dependent trafficking of cardiac voltage-gated L-type Ca2+ channels through PKD1. Circ Res. 2012, 110: 59-70. PMCID: PMC4232192 (*Equal Contribution)
11. Yoon Y, Galloway CA, Jhun BS, Yu T: Mitochondrial Dynamics in Diabetes. Antioxid Redox Signal. 2011, 14(3): 439-457. PMCID: PMC3025181
12. Yu T, Jhun BS, Yoon Y: High-Glucose Stimulation Increases Reactive Oxygen Species Production Through the Calcium and Mitogen-Activated Protein Kinase-Mediated Activation of Mitochondrial Fission. Antioxid Redox Signal. 2011, 14(3): 425-437. PMCID: PMC3025178