Department of Pharmacology NUS Medicine

𝐈𝐍𝐓𝐑𝐎𝐃𝐔𝐂𝐓𝐈𝐎𝐍
Cortical cerebral microinfarcts (CMIs) are associated with cognitive dysfunction and dementia, while their evolution on sequential magnetic resonance imaging (MRI) remains unclear.

𝐌𝐄𝐓𝐇𝐎𝐃𝐒
The study enrolled 490 patients (72.5 ± 7.9 years) from a memory-clinic cohort, with 5-year follow-up. Cortical CMIs were graded at baseline and year 2 to identify incident lesions and other evolutionary patterns. Cognitive function was assessed annually. Clinical events, including dementia, stroke, and mortality, were recorded with time to event.

𝐑𝐄𝐒𝐔𝐋𝐓𝐒
Forty-one (8.4%) patients showed incident cortical CMIs at year 2. Additionally, 12 had CMIs becoming invisible, and six showed CMIs incorporated into new large infarctions. Baseline cortical CMIs and large cortical infarcts showed the strongest association with incident CMIs. Incident cortical CMIs were associated with cognitive decline, white matter hyperintensity progression, and incident dementia, independent of prevalent lesions.

𝐃𝐈𝐒𝐂𝐔𝐒𝐒𝐈𝐎𝐍
Cortical CMI evolution may reflect dynamic changes in brain vascular pathology and represent a potential target for interventions aimed at preserving cognitive function.

We are pleased to announce that Dr TRAN Thi Tuyet Trinh has been awarded the Lilly Medal and Prize in Pharmacology 2026 in recognition of her outstanding PhD research.

This annual award was established through a donation from the Lilly-NUS Centre for Clinical Pharmacology Pte Ltd, a subsidiary of Eli Lilly and Company, to honour students who have excelled in pharmacology studies and training. The prize includes a gold medal and a cash award of S$250 for the PhD student with the best PhD research thesis in Pharmacology.

Dr Tran’s thesis, “RNA Therapeutics Targeting Driver Mutations in Non-Small Cell Lung Cancer Delivered by Extracellular Vesicles,” was supervised by Associate Professor LE Thi Nguyet Minh from the Department of Pharmacology and the Digital Medicine (WisDM) Translational Research Programme.

We extend our heartfelt congratulations to Dr TRAN Thi Tuyet Trinh on this well-deserved achievement, and our sincere appreciation to the principal investigators for their strong support of this prize.

𝐁𝐚𝐜𝐤𝐠𝐫𝐨𝐮𝐧𝐝
Gastric cancer, the fifth most prevalent cancer globally, poses significant treatment challenges due to factors such as late diagnosis, early metastasis, limited surgical options, and the systemic toxicity of chemotherapy. Because luminal barriers are often compromised in gastric cancers , orally administered therapies that enable localized absorption and drug release represent a promising new direction for site-specific treatment with limited side effects.

𝐑𝐞𝐬𝐮𝐥𝐭𝐬
We introduce a disulfide-linked thermostable exoshell system that orally delivers protein-based bioorthogonal catalytic centres directly to cancer tissues. The highly engineered exoshells effectively encapsulated and stabilized labile catalytic centres, preventing degradation in the harsh gastric environment. In vivo gastric tumors were treated using the anti-cancer properties of active metabolites of the prodrug indole-3-acetic acid (IAA) converted in situ via bioorthogonal catalysis. In vitro cell studies revealed a dose- and time-dependent inhibition of gastric cancer cell growth, irrespective of their HER2 status. This inhibition was accompanied by upregulation of mitochondrial lipid peroxidation, reduced mitochondrial membrane potential, and activation of necroptotic pathway markers such as RIP1, RIP3, and MLKL at both mRNA and protein levels. In a mouse model of gastric cancer induced by N-Methyl-N-Nitrosourea, oral administration of catalytic exoshells for 6 weeks significantly inhibited gastric inflammation and tumour polyp growth. Additionally, LC/MS/MS-based metabolomic analysis of plasma obtained from treated mice showed significant upregulation of cytotoxic metabolites of IAA. Notably, metabolites relevant to redox regulation, including alpha-tocopherol (vitamin E), glutathione (GSH), homocysteine, methyl cysteine, and cysteine sulfinic acid, were identified as the top differentially expressed metabolites, indicating potent suppression of inflammation and tumour growth. Histological analysis of gastric tissue showed a reduced number of polyps and subsequent development of gastric tumours.

𝐂𝐨𝐧𝐜𝐥𝐮𝐬𝐢𝐨𝐧
Our in vitro and in vivo results demonstrated that exoshells possessed significant potential as an orally administered, titratable therapeutic platform for the management of gastrointestinal cancers.

Congratulations to faculty members from the Department of Pharmacology who have been featured in the latest Research.com global rankings of Best Scientists by Discipline. These prestigious rankings recognise leading experts worldwide based on their research performance, impact, and scholarly contributions.

We are especially proud to share that Professor Guillermo C. Bazan was ranked 2nd in Singapore and 98th globally in Chemistry, underscoring his outstanding influence in the field.

Notably, most of the recognised faculty demonstrated improvements in their global rankings, while their national rankings remained unchanged, reflecting continued strong standing within Singapore alongside growing international research impact. Distinguished faculty members recognised across disciplines such as Medicine, Neuroscience, and Biology & Biochemistry include Associate Professor Gautam Sethi, Dr Alan Prem Kumar, Dr Mitchell Lai Kim Peng, Associate Professor Gavin S. Dawe, Professor Manjunatha Kini, Dr Muthu Shanmugam, Associate Professor Edward Manser, Associate Professor Shabbir Moochhala, Professor Phillip K. Moore, and Professor Christopher Chen Li-Hsian.

These achievements highlight the Department of Pharmacology’s sustained excellence in biomedical research and its rising global visibility, while maintaining leadership at the national level.

Calling all International Applicants! ✈️ 🌍

Applications for the 𝐌𝐚𝐬𝐭𝐞𝐫 𝐨𝐟 𝐒𝐜𝐢𝐞𝐧𝐜𝐞 𝐢𝐧 𝐌𝐞𝐝𝐢𝐜𝐚𝐥 𝐏𝐡𝐚𝐫𝐦𝐚𝐜𝐨𝐥𝐨𝐠𝐲 𝐚𝐭 𝐍𝐔𝐒 (Aug 2026 Intake) are closing very soon!

Please submit your applications by 𝟑𝟏𝐬𝐭 𝐌𝐚𝐲 𝟐𝟎𝟐𝟔.

For more information and where to apply please head to our website:

https://medicine.nus.edu.sg/graduatestudies/education/msc-in-medical-pharmacology/

Ensure you have the required documents which include:
1. Academic transcripts and CV
2. Statement of Intent
3. Personal Statement
4. Proof of English proficiency (IELTS or TOEFL)
5. Financial Support documents.

All the best!!

We are proud to congratulate our faculty members — Prof. Christopher CHEN Li Hsian, Prof. GOH Boon Cher, and Dr. Saima HILAL — on receiving prestigious awards under the 2026 National Medical Research Council (NMRC) Awards.

Prof Christopher Chen and Prof Goh Boon Cher were awarded the Singapore Translational Research Investigator Award (STaR), while Dr Saima Hilal received the Clinician Scientist Award – Investigator (CSA-INV).

These achievements reflect their outstanding contributions to medical research and their continued commitment to advancing healthcare and scientific innovation. We extend our heartfelt congratulations on this well-deserved recognition.

𝐈𝐍𝐓𝐑𝐎𝐃𝐔𝐂𝐓𝐈𝐎𝐍
Vascular dementia (VaD) is a major therapeutic challenge. Tar DNA-binding protein 43 (TDP-43), known for its role in neurodegeneration, may contribute to VaD pathogenesis under chronic cerebral hypoperfusion (CCH). This study investigates TDP-43 dysregulation in VaD.

𝐌𝐄𝐓𝐇𝐎𝐃𝐒
TDP-43 and phosphorylated TDP-43 (pTDP-43) expression and localization were assessed in a VaD animal model, neuronal cells exposed to oxygen–glucose deprivation (OGD), and post mortem human brain tissues.

𝐑𝐄𝐒𝐔𝐋𝐓𝐒
Bilateral Common Carotid Artery Stenosis (BCAS)-induced CCH led to increased pTDP-43 and aberrant redistribution of both TDP-43 and pTDP-43. In vitro OGD triggered similar mislocalization. Post mortem VaD brains showed no TDP-43 abnormalities, while Alzheimer’s and mixed dementia cases exhibited marked pathology.

𝐃𝐈𝐒𝐂𝐔𝐒𝐒𝐈𝐎𝐍
TDP-43 dysregulation appears early in VaD under hypoperfusive stress, distinguishing it from other dementia subtypes. These findings indicate that TDP‑43 may warrant further investigation as a potential early molecular feature of VaD.

Full Article: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71196

INTRODUCTION

Genome-wide association studies have identified numerous Alzheimer’s disease (AD) susceptibility loci in European populations. However, the genetic architecture of AD in non-European populations remains underinvestigated.
METHODS

We performed a genetic association study in East Asians (N = 8514) to validate known AD loci and identify new susceptibility loci.
RESULTS

We identified LILRB2–LILRB5 as an AD susceptibility locus with ethnic-specific effects between Europeans and East Asians. The lead variant, rs587709-T, was associated with decreased AD risk and increased LILRB5 expression in Europeans. Conversely, in East Asians, the same allele was associated with increased AD risk and increased LILRB2 expression. Furthermore, genome-wide analysis identified TTC3 and FAM135A as candidate susceptibility loci for AD or cognition.
DISCUSSION

The results establish LILRB2–LILRB5 as a cross-ancestry AD-associated locus with ethnic-specific genetic mechanisms and reveal new susceptibility loci, extending the understanding of the genetic etiology of AD.

Full Article: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71219

Among the transcriptional regulators of cell fate, c-Myc is one of the most frequently deregulated oncogenes, exerting pleiotropic effects on cellular metabolism, survival, and stress adaptation. C-Myc occupies a pivotal position at the intersection of autophagy and senescence, two essential, yet paradoxical processes in cancer biology. Autophagy can both suppress tumor formation and support the survival of established tumors. In contrast, senescence acts as a barrier to malignant transformation but can also promote tumor progression through the senescence-associated secretory phenotype. C-Myc modulates both autophagy and senescence in a highly context-dependent manner. It acts as either an inducer or a suppressor depending on cellular state and microenvironmental conditions. This dual regulatory capacity underscores its role as a central hub in cell fate decisions. In this review, we first summarize how c-Myc, autophagy, and senescence contribute to tumor biology. We then highlight the molecular mechanisms through which c-Myc regulates autophagy and senescence. We examine how these interactions influence cancer progression. Finally, we discuss emerging therapeutic strategies and clinical trials targeting the c-Myc-mediated autophagy/senescence axis. We also address future challenges and opportunities for exploiting this network in precision oncology.

Full Article: https://www.sciencedirect.com/science/article/abs/pii/S0304383526000789?via%3Dihub

As in art, the ability of nucleic acids to be designed and synthesized as a novel treatment modality is limited only by the imagination. Nucleic acids of virtually all sizes and forms can be synthesized on demand, from short antisense oligonucleotides to large mRNAs and to entire chromosomes. Given the genetic basis of cancer, nucleic acid-based therapy is a particularly promising avenue for anticancer therapeutic development. This has led to a profusion of studies exploring strategies to utilize nucleic acid-based drugs to treat cancer, with some approaches demonstrating great potential for clinical translation. In this review, we summarize the various nucleic acid-based strategies being developed for cancer therapy. We also provide a comprehensive overview of current efforts to enhance the potency and safety of nucleic acid-based drugs, exploring advances in nucleotide composition, design, and delivery strategies.
Full Article: https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(25)00812-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1525001625008123%3Fshowall%3Dtrue