Joanne Soh Ern Chi

@shiga-med.ac.jp

Department of Biochemistry and Molecular Biology
Shiga University of Medical Science

Joanne Soh Ern Chi


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https://researchid.co/drsohjec
A research scientist in the field of cardiovascular and kidney research

EDUCATION

PhD in Medical Science, Shiga University of Medical Science (SUMS), Japan
MSc in Molecular Medicine, UMBI, University of Kebangsaan Malaysia (UKM), Malaysia
BSc in Biotechnology (Hons), INTI International University, Malaysia

RESEARCH, TEACHING, or OTHER INTERESTS

General Biochemistry, Genetics and Molecular Biology, Molecular Medicine, Cancer Research, Cell Biology
10

Scopus Publications

123

Scholar Citations

7

Scholar h-index

5

Scholar i10-index

Scopus Publications

  • The role of the tricellular junction protein ILDR2 in glomerulopathies: Expression patterns and functional insights
    Florian Siegerist, Felix Kliewe, Elke Hammer, Paul Schakau, Joanne Ern Chi Soh, Claudia Weber, Maja Lindenmeyer, Simone Reichelt-Wurm, Vedran Drenic, Christos Chatziantoniou, Christos E. Chadjichristos, Yiying Zhang, Stefan Simm, Miriam C. Banas, Matthias Nauck, Uwe Völker, Nicole Endlich
    Iscience, 2024
    knockout mice exhibited glomerular hypertrophy and decreased podocyte density. However, they did not develop effacement of podocyte foot processes or proteinuria. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis of isolated glomeruli showed an increase in matrix proteins, such as fibronectin and collagens. This suggests a protective role of ILDR2 in glomerulopathies.
  • Novel cardiovascular protective effects of RhoA signaling and its therapeutic implications
    Joanne Ern Chi Soh, Akio Shimizu, Akira Sato, Hisakazu Ogita
    Biochemical Pharmacology, 2023
    Ras homolog gene family member A (RhoA) belongs to the Rho GTPase superfamily, which was first studied in cancers as one of the essential regulators controlling cellular function. RhoA has long attracted attention as a key molecule involved in cell signaling and gene transcription, through which it affects cellular processes. A series of studies have demonstrated that RhoA plays crucial roles under both physiological states and pathological conditions in cardiovascular diseases. RhoA has been identified as an important regulator in cardiac remodeling by regulating actin stress fiber dynamics and cytoskeleton formation. However, its underlying mechanisms remain poorly understood, preventing definitive conclusions being drawn about its protective role in the cardiovascular system. In this review, we outline the characteristics of RhoA and its related signaling molecules, and present an overview of RhoA classical function and the corresponding cellular responses of RhoA under physiological and pathological conditions. Overall, we provide an update on the novel signaling under RhoA in the cardiovascular system and its potential clinical and therapeutic targets in cardiovascular medicine.
  • RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy
    Joanne Ern Chi Soh, Akio Shimizu, Md Rasel Molla, Dimitar P. Zankov, Le Kim Chi Nguyen, Mahbubur Rahman Khan, Wondwossen Wale Tesega, Si Chen, Misa Tojo, Yoshito Ito, Akira Sato, Masahito Hitosugi, Shigeru Miyagawa, Hisakazu Ogita
    Journal of Biological Chemistry, 2023
    Heart failure is one of the leading causes of death worldwide. RhoA, a small GTPase, governs actin dynamics in various tissue and cell types, including cardiomyocytes; however, its involvement in cardiac function has not been fully elucidated. Here, we generated cardiomyocyte-specific RhoA conditional knockout (cKO) mice, which demonstrated a significantly shorter lifespan with left ventricular dilation and severely impaired ejection fraction. We found that the cardiac tissues of the cKO mice exhibited structural disorganization with fibrosis and also exhibited enhanced senescence compared with control mice. In addition, we show that cardiomyocyte mitochondria were structurally abnormal in the aged cKO hearts. Clearance of damaged mitochondria by mitophagy was remarkably inhibited in both cKO cardiomyocytes and RhoA-knockdown HL-1 cultured cardiomyocytes. In RhoA-depleted cardiomyocytes, we reveal that the expression of Parkin, an E3 ubiquitin ligase that plays a crucial role in mitophagy, was reduced, and expression of N-Myc, a negative regulator of Parkin, was increased. We further reveal that the RhoA-Rho kinase axis induced N-Myc phosphorylation, which led to N-Myc degradation and Parkin upregulation. Re-expression of Parkin in RhoA-depleted cardiomyocytes restored mitophagy, reduced mitochondrial damage, attenuated cardiomyocyte senescence, and rescued cardiac function both in vitro and in vivo. Finally, we found that patients with idiopathic dilated cardiomyopathy without causal mutations for dilated cardiomyopathy showed reduced cardiac expression of RhoA and Parkin. These results suggest that RhoA promotes Parkin-mediated mitophagy as an indispensable mechanism contributing to cardioprotection in the aging heart.
  • Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity
    Md Rasel Molla, Akio Shimizu, Masahiro Komeno, Nor Idayu A. Rahman, Joanne Ern Chi Soh, Le Kim Chi Nguyen, Mahbubur Rahman Khan, Wondwossen Wale Tesega, Si Chen, Xiaoling Pang, Miki Tanaka-Okamoto, Noriyuki Takashima, Akira Sato, Tomoaki Suzuki, Hisakazu Ogita
    Communications Biology, 2022
    Whether a small GTPase RhoA plays a role in the pathology of abdominal aortic aneurysm (AAA) has not been determined. We show here that RhoA expression is reduced in human AAA lesions, compared with normal areas. Furthermore, incidence of AAA formation is increased in vascular smooth muscle cell (VSMC)-specific RhoA conditional knockout (cKO) mice. The contractility of the aortic rings and VSMCs from RhoA cKO mice is reduced, and expression of genes related to the VSMC contractility is attenuated by loss of RhoA. RhoA depletion activates the mitogen-activated protein (MAP) kinase signaling, including MAP4K4, in the aorta and VSMCs. Inhibition of MAP4K4 activity by DMX-5804 decreases AAA formation. Set, a binding protein to active RhoA, functions as an activator of MAP4K4 by sequestering PP2A, an inhibitor of MAP4K4, in the absence of RhoA. In conclusion, RhoA counteracts AAA formation through inhibition of MAP4K4 in cooperation with Set.
  • Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αb-crystallin intracellular dynamics
    Le Kim Chi Nguyen, Akio Shimizu, Joanne Ern Chi Soh, Masahiro Komeno, Akira Sato, Hisakazu Ogita
    Journal of Biochemistry, 2021
    Transmembrane protein 168 (TMEM168) was found to be localized on the nuclear membrane. A heterozygous mutation (c.1616G>A, p. R539Q) in TMEM168 was identified in patients with Brugada syndrome. This mutation reduced expression of cardiomyocyte sodium channel Nav1.5 via Nedd4-2 E3 ubiquitin ligase-induced ubiquitination and degradation. However, the detailed molecular mechanism provoked by the TMEM168 mutant remains unclear. Here, we demonstrated that small heat shock protein αB-crystallin, which can bind to Nav1.5 and Nedd4-2 and interfere with the association of both proteins, was strongly recruited from the cell surface to the perinuclear region because of the much higher affinity of αB-crystallin with the TMEM168 mutant than with wild-type TMEM168. Following knockdown of αB-crystallin in HL-1 cardiomyocytes, the interaction of Nav1.5 with Nedd4-2 was increased, despite the reduced expression of Nav1.5. Moreover, reduction of Nav1.5 expression by αB-crystallin knockdown was rescued in the presence of a proteasome inhibitor MG-132, suggesting the importance of the αB-crystallin-modulated ubiquitin–proteasome system for the stability of Nav1.5 expression. Collectively, the balance of molecular interactions among Nav1.5, Nedd4-2 and αB-crystallin plays a role in the regulation of cardiomyocyte cell surface expression of Nav1.5, and the TMEM168 mutant disturbs this balance, resulting in a decrease in Nav1.5 expression.
  • Stomatin-mediated inhibition of the akt signaling axis suppresses tumor growth
    Nor Idayu A. Rahman, Akira Sato, Khurelbaatar Tsevelnorov, Akio Shimizu, Masahiro Komeno, Mohammad Khusni Bin Ahmat Amin, Md Rasel Molla, Joanne Ern Chi Soh, Le Kim Chi Nguyen, Akinori Wada, Akihiro Kawauchi, Hisakazu Ogita
    Cancer Research, 2021
    The growth and progression of cancers are crucially regulated by the tumor microenvironment where tumor cells and stromal cells are mutually associated. In this study, we found that stomatin expression was markedly upregulated by the interaction between prostate cancer cells and stromal cells. Stomatin suppressed cancer cell proliferation and enhanced apoptosis in vitro and inhibited xenograft tumor growth in vivo. Stomatin inhibited Akt activation, which is mediated by phosphoinositide-dependent protein kinase 1 (PDPK1). PDPK1 protein stability was maintained by its binding to HSP90. Stomatin interacted with PDPK1 and interfered with the PDPK1–HSP90 complex formation, resulting in decreased PDPK1 expression. Knockdown of stomatin in cancer cells elevated Akt activation and promoted cell increase by promoting the interaction between PDPK1 and HSP90. Clinically, stomatin expression levels were significantly decreased in human prostate cancer samples with high Gleason scores, and lower expression of stomatin was associated with higher recurrence of prostate cancer after the operation. Collectively, these findings demonstrate the tumor-suppressive effect of stromal-induced stomatin on cancer cells. Significance: These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis.
  • Cardio- And reno-protective effects of dipeptidyl peptidase iii in diabetic mice
    Masahiro Komeno, Xiaoling Pang, Akio Shimizu, Md Rasel Molla, Mako Yasuda-Yamahara, Shinji Kume, Nor Idayu A. Rahman, Joanne Ern Chi Soh, Le Kim Chi Nguyen, Mohammad Khusni B. Ahmat Amin, Nao Kokami, Akira Sato, Yoshihiro Asano, Hiroshi Maegawa, Hisakazu Ogita
    Journal of Biological Chemistry, 2021
    Diabetes mellitus (DM) causes injury to tissues and organs, including to the heart and kidney, resulting in increased morbidity and mortality. Thus, novel potential therapeutics are continuously required to minimize DM-related organ damage. We have previously shown that dipeptidyl peptidase III (DPPIII) has beneficial roles in a hypertensive mouse model, but it is unknown whether DPPIII has any effects on DM. In this study, we found that intravenous administration of recombinant DPPIII in diabetic db/db mice for 8 weeks suppressed the DM-induced cardiac diastolic dysfunctions and renal injury without alteration of the blood glucose level. This treatment inhibited inflammatory cell infiltration and fibrosis in the heart and blocked the increase in albuminuria by attenuating the disruption of the glomerular microvasculature and inhibiting the effacement of podocyte foot processes in the kidney. The beneficial role of DPPIII was, at least in part, mediated by the cleavage of a cytotoxic peptide, named Peptide 2, which was increased in db/db mice compared with normal mice. This peptide consisted of nine amino acids, was a digested fragment of complement component 3 (C3), and had an anaphylatoxin-like effect determined by the Miles assay and chemoattractant analysis. The effect was dependent on its interaction with the C3a receptor and protein kinase C-mediated RhoA activation downstream of the receptor in endothelial cells. In conclusion, DPPIII plays a protective role in the heart and kidney in a DM animal model through cleavage of a peptide that is a part of C3.
  • Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index
    Nadiah Abu, Norahayu Othman, Nur’ Syahada Ab Razak, Nurul Ainaa’ Adilah Rus Bakarurraini, Siti Nurmi Nasir, Joanne Ern Chi Soh, Luqman Mazlan, Zairul Azwan Mohd Azman, Rahman Jamal
    Frontiers in Cell and Developmental Biology, 2020
    Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.
  • The potential immune-eliciting cancer testis antigens in colorectal cancer
    Joanne Ern Chi Soh, Nadiah Abu, Rahman Jamal
    Immunotherapy, 2018
    The identification of cancer testis antigens (CTAs) has been an important finding in the search of potential targets for cancer immunotherapy. CTA is one of the subfamilies of the large tumor-associated antigens groups. It is aberrantly expressed in various types of human tumors but is absent in normal tissues except for the testis and placenta. This CTAs-restricted pattern of expression in human malignancies together with its potential immunogenic properties, has stirred the interest of many researchers to use CTAs as one of the ideal targets in cancer immunotherapy. To date, multiple studies have shown that CTAs-based vaccines can elicit clinical and immunological responses in different tumors, including colorectal cancer (CRC). This review details our current understanding of CTAs and CRC in regard to the expression and immunological responses as well as some of the critical hurdles in CTAs-based immunotherapy.
  • Isolation and identification of fungi from polluted soil in Peninsular Malaysia for copper remediation
    Pollution Research, 2017

RECENT SCHOLAR PUBLICATIONS

  • Novel cardiovascular protective effects of RhoA signaling and its therapeutic implications
    JEC Soh, A Shimizu, A Sato, H Ogita
    Biochemical Pharmacology 218, 115899 , 2023
    2023.0
    Citations: 8
  • RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy
    JEC Soh, A Shimizu, MR Molla, DP Zankov, LKC Nguyen, MR Khan, ...
    Journal of Biological Chemistry 299 (3) , 2023
    2023.0
    Citations: 29
  • Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity
    MR Molla, A Shimizu, M Komeno, NIA Rahman, JEC Soh, LKC Nguyen, ...
    Communications Biology 5 (1), 1071 , 2022
    2022.0
    Citations: 16
  • Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Na v 1.5 through αB-crystallin intracellular dynamics
    LKC Nguyen, A Shimizu, JEC Soh, M Komeno, A Sato, H Ogita
    The Journal of Biochemistry 170 (5), 577-585 , 2021
    2021.0
    Citations: 4
  • Stomatin-mediated inhibition of the Akt signaling axis suppresses tumor growth
    NIA Rahman, A Sato, K Tsevelnorov, A Shimizu, M Komeno, ...
    Cancer research 81 (9), 2318-2331 , 2021
    2021.0
    Citations: 14
  • Cardio-and reno-protective effects of dipeptidyl peptidase III in diabetic mice
    M Komeno, X Pang, A Shimizu, MR Molla, M Yasuda-Yamahara, S Kume, ...
    Journal of Biological Chemistry 296, 100761 , 2021
    2021.0
    Citations: 19
  • Extracellular vesicles derived from colorectal cancer affects CD8 T cells: An analysis based on body Mass index
    N Abu, N Othman, NS Ab Razak, NAAR Bakarurraini, SN Nasir, JEC Soh, ...
    Frontiers in Cell and Developmental Biology 8, 564648 , 2020
    2020.0
    Citations: 9
  • Validation of immunogenic PASD1 peptides against HLA-A* 24: 02 colorectal cancer
    JEC Soh, N Abu, I Sagap, L Mazlan, A Yahaya, M Mustangin, TS Khoo, ...
    Immunotherapy 11 (14), 1205-1219 , 2019
    2019.0
    Citations: 6
  • The potential immune-eliciting cancer testis antigens in colorectal cancer
    JE Chi Soh, N Abu, R Jamal
    Immunotherapy 10 (12), 1093-1104 , 2018
    2018.0
    Citations: 11
  • Isolation and identification of fungi from polluted soil in Peninsular Malaysia for copper remediation
    GH Ong, C Leeraj, J Soh, LS Wong
    Pollution Research Paper 36 (1), 18-21 , 2017
    2017.0
    Citations: 7
  • Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1. 5 through aB-crystallin intracellular dynamics
    JEC Soh, M Komeno, A Sato, H Ogita

MOST CITED SCHOLAR PUBLICATIONS

  • RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy
    JEC Soh, A Shimizu, MR Molla, DP Zankov, LKC Nguyen, MR Khan, ...
    Journal of Biological Chemistry 299 (3) , 2023
    2023.0
    Citations: 29
  • Cardio-and reno-protective effects of dipeptidyl peptidase III in diabetic mice
    M Komeno, X Pang, A Shimizu, MR Molla, M Yasuda-Yamahara, S Kume, ...
    Journal of Biological Chemistry 296, 100761 , 2021
    2021.0
    Citations: 19
  • Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity
    MR Molla, A Shimizu, M Komeno, NIA Rahman, JEC Soh, LKC Nguyen, ...
    Communications Biology 5 (1), 1071 , 2022
    2022.0
    Citations: 16
  • Stomatin-mediated inhibition of the Akt signaling axis suppresses tumor growth
    NIA Rahman, A Sato, K Tsevelnorov, A Shimizu, M Komeno, ...
    Cancer research 81 (9), 2318-2331 , 2021
    2021.0
    Citations: 14
  • The potential immune-eliciting cancer testis antigens in colorectal cancer
    JE Chi Soh, N Abu, R Jamal
    Immunotherapy 10 (12), 1093-1104 , 2018
    2018.0
    Citations: 11
  • Extracellular vesicles derived from colorectal cancer affects CD8 T cells: An analysis based on body Mass index
    N Abu, N Othman, NS Ab Razak, NAAR Bakarurraini, SN Nasir, JEC Soh, ...
    Frontiers in Cell and Developmental Biology 8, 564648 , 2020
    2020.0
    Citations: 9
  • Novel cardiovascular protective effects of RhoA signaling and its therapeutic implications
    JEC Soh, A Shimizu, A Sato, H Ogita
    Biochemical Pharmacology 218, 115899 , 2023
    2023.0
    Citations: 8
  • Isolation and identification of fungi from polluted soil in Peninsular Malaysia for copper remediation
    GH Ong, C Leeraj, J Soh, LS Wong
    Pollution Research Paper 36 (1), 18-21 , 2017
    2017.0
    Citations: 7
  • Validation of immunogenic PASD1 peptides against HLA-A* 24: 02 colorectal cancer
    JEC Soh, N Abu, I Sagap, L Mazlan, A Yahaya, M Mustangin, TS Khoo, ...
    Immunotherapy 11 (14), 1205-1219 , 2019
    2019.0
    Citations: 6
  • Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Na v 1.5 through αB-crystallin intracellular dynamics
    LKC Nguyen, A Shimizu, JEC Soh, M Komeno, A Sato, H Ogita
    The Journal of Biochemistry 170 (5), 577-585 , 2021
    2021.0
    Citations: 4
  • Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1. 5 through aB-crystallin intracellular dynamics
    JEC Soh, M Komeno, A Sato, H Ogita