Article
Biochemistry & Molecular Biology
Emmy Xue Yun Tay, Kimberly Chia, Derrick Sek Tong Ong
Summary: Neural stem cells are crucial for normal brain development and are regulated by redox and epigenetic mechanisms. How this crosstalk impacts NSC activity remains poorly understood, as well as their contribution to brain ageing and neurodegenerative diseases. Therapeutic opportunities based on redox and epigenetic regulations are highlighted for rescuing NSC dysfunctions.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Multidisciplinary Sciences
Jeehyun Yoon, Oleg Grinchuk, Srinivasaraghavan Kannan, Melgious Jin Yan Ang, Zhenglin Li, Emmy Xue Yun Tay, Ker Zhing Lok, Bernice Woon Li Lee, You Heng Chuah, Kimberly Chia, Roberto Tirado Magallanes, Chenfei Liu, Haonan Zhao, Jin Hui Hor, Jhin Jieh Lim, Touati Benoukraf, Tan Boon Toh, Edward Kai-Hua Chow, Jean-Paul Kovalik, Jianhong Ching, Shi-Yan Ng, Ming Joo Koh, Xiaogang Liu, Chandra Shekhar Verma, Derrick Sek Tong Ong
Summary: The study reveals the dependency of GBM on biotin distribution, suggesting that rational cotargeting of biotin-dependent metabolism and epigenetic pathways may be explored for GSC eradication.
Article
Chemistry, Multidisciplinary
Melgious Jin Yan Ang, Jeehyun Yoon, Mingzhu Zhou, Han-Lin Wei, Yi Yiing Goh, Zhenglin Li, Jia Feng, Haifang Wang, Qianqian Su, Derrick Sek Tong Ong, Xiaogang Liu
Summary: Nanoparticles modified with ligands can cross the blood-brain barrier, endocytose into the lysosomes of glioblastoma cells, and undergo endolysosomal escape under photochemical ionization. Metronomic chemotherapy using dual-drug-loaded nanocarriers can induce an enhanced antitumor effect 3.5 times greater than standard chemotherapy.
ADVANCED MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Jeehyun Yoon, Oleg Grinchuk, Roberto Tirado-Magallanes, Zhen Kai Ngian, Emmy Xue Yun Tay, You Heng Chuah, Bernice Woon Li Lee, Jia Feng, Karen Carmelina Crasta, Chin Tong Ong, Touati Benoukraf, Derrick Sek Tong Ong
Summary: The histone variant H2AZ is overexpressed in glioblastomas (GBM) and glioma stem cells (GSCs), promoting their proliferation and tumorigenicity. E2F1 and STAT3 synergistically activate H2AZ gene transcription in GSCs, and an E2F/STAT3 inhibitor combination shows promise in suppressing GSC tumorigenicity in GBM treatment.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Fabrizio Chiti, Jeffery W. Kelly
Summary: Protein misfolding diseases are caused by structural abnormalities in proteins, and specific small molecules have been approved to stabilize the folded state of these proteins, providing a promising approach to treat such diseases.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Nicholas L. Yan, Reji Nair, Alan Chu, Ian A. Wilson, Kristen A. Johnson, Gareth J. Morgan, Jeffery W. Kelly
Summary: This study investigates the potential of finding small molecule kinetic stabilizers in immunoglobulin light chain amyloidosis, identifying coumarin-based compounds with potential therapeutic effects. Structural-activity relationship data reveals that these compounds bind at different sites in the LC dimer, exerting unique stabilizing effects on LCs.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Gabriel M. Kline, Karina Nugroho, Jeffery W. Kelly
Summary: In this review, we examine the application of Inverse Drug Discovery method using organic compounds of intermediate complexity harboring Sulfur(VI)-fluoride exchange (SuFEx) electrophiles to expand the cellular proteins that can be targeted covalently.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Meng Wang, Edmund Cotter, Ya-Juan Wang, Xu Fu, Angela L. Whittsette, Joseph W. Lynch, R. Luke Wiseman, Jeffery W. Kelly, Angelo Keramidas, Ting-Wei Mu
Summary: This study demonstrates that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis can increase the assembly, trafficking, and surface expression of variant GABA(A) receptors, offering a potential opportunity to mitigate pathology associated with genetic epilepsy and other disease-associated variant ion channels.
CELL AND BIOSCIENCE
(2022)
Article
Cell Biology
Jaleh S. Mesgarzadeh, Isabelle C. Romine, Ethan M. Smith-Cohen, Julia M. D. Grandjean, Jeffery W. Kelly, Joseph C. Genereux, R. Luke Wiseman
Summary: This study identified ER proteostasis factors involved in ATF6-dependent reductions in destabilized TTR secretion through a mass-spectrometry-based interactomics approach. Activation of ATF6 reduces the secretion and subsequent aggregation of amyloidogenic TTR through increased interactions with ATF6-regulated ER proteostasis factors including BiP and PDIA4. PDIA4 retains destabilized TTR in the ER through a redox-independent mechanism. These findings provide a mechanistic basis for the therapeutic targeting of ATF6 activation to improve treatments for TTR-related amyloid diseases.
Article
Cell Biology
Jiaqing Chen, Li Zou, Guang Lu, Oleg Grinchuk, Lei Fang, Derrick Sek Tong Ong, Reshma Taneja, Choon-Nam Ong, Han-Ming Shen
Summary: This study reveals the important role of PFKP in non-small-cell lung cancer (NSCLC), showing that PFKP interacts with AMPK to promote mitochondrial recruitment of AMPK and enhance phosphorylation of ACC2, ultimately promoting long-chain fatty acid oxidation and cancer cell survival under glucose starvation.
Article
Geriatrics & Gerontology
Mathew S. Maurer, Dia Smiley, Eli Simsolo, Fabrizio Remotti, Angela Bustamante, Sergio Teruya, Stephen Helmke, Andrew J. Einstein, Ronald Lehman, Jon T. Giles, Jeffery W. Kelly, Felix Tsai, William S. Blaner, Pierre-Jacques Brun, Ron Riesenburger, James Kryzanski, Cindy Varga, Ayan R. Patel
Summary: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in older adults, with amyloid detected in over one third of patients, especially in those over 75 years old. Age, clinical symptoms, cardiac biomarkers, and other parameters did not differ significantly between patients with and without amyloid.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Tushar Warrier, Chadi El Farran, Yingying Zeng, Benedict Shao Quan Ho, Qiuye Bao, Zi Hao Zheng, Xuezhi Bi, Huck Hui Ng, Derrick Sek Tong Ong, Justin Jang Hann Chu, Amartya Sanyal, Melissa Jane Fullwood, James J. Collins, Hu Li, Jian Xu, Yuin-Han Loh
Summary: SETDB1 regulates lineage-specific genes and endogenous retroviral elements through H3K9me3 deposition. In addition, it co-regulates target gene expression and genome topology with the topological regulator Cohesin at DiSCs, which are regions proximal to gene promoters involved in embryonic stem cell pluripotency and lineage development. This discovery is important for understanding the maintenance and differentiation of embryonic stem cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Cecilia Monteiro, Jaleh S. Mesgarzadeh, Joao Anselmo, Joana Fernandes, Marta Novais, Carla Rodrigues, David L. Powers, Evan T. Powers, Teresa Coelho, Jeffery W. Kelly
Summary: This study explored the relationship between TTR stabilization markers and clinical efficacy of tafamidis treatment. The results showed an increase in native TTR concentration and a decrease in non-native TTR concentration. However, changes in native and non-native TTR levels were not correlated with clinical response to tafamidis. Successful tafamidis therapy requires moderate TTR stabilization, and male patients may benefit from higher doses of tafamidis.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Felix J. J. Tsai, Luke T. T. Nelson, Gabriel M. M. Kline, Marcus Jager, John L. L. Berk, Yoshiki Sekijima, Evan T. T. Powers, Jeffery W. Kelly
Summary: This study investigated the plasma concentrations of diflunisal and its efficacy in treating TTR polyneuropathy, finding that at a certain concentration, diflunisal can effectively slow down TTR dissociation rate and inhibit aggregation.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Oncology
Nandini Karthik, Jane Jia Hui Lee, Joshua Ling Jun Soon, Hsin Yao Chiu, Amos Hong Pheng Loh, Derrick Sek Tong Ong, Wai Leong Tam, Reshma Taneja
Summary: This study reveals that histone variant H3.3 is overexpressed in alveolar rhabdomyosarcoma (ARMS), impacting the migration and invasion ability of tumor cells and correlating with metastasis and prognosis in ARMS. Mechanistically, melanoma cell adhesion molecule (MCAM) is identified as a direct downstream target of H3.3, and its overexpression rescues cell migration and invasion in H3F3A-depleted cells. Furthermore, G9a, an upstream regulator of H3F3A, is discovered. This study uncovers a novel H3.3-dependent axis and establishes the potential of MCAM as a therapeutic target for high-risk ARMS patients.
JOURNAL OF PATHOLOGY
(2023)