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
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, et al. 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, et al. 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, et al. 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.
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, et al. 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
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
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