Research

Programs spanning fly genetics, human neuronal models, and therapeutic discovery.

Our research is organised around four complementary programs — two core discovery lines focused on neuronal resilience and motor neuron disease, and two collaborative platforms that translate mechanistic insight into rare-disease modeling and therapeutic testing.

Figure · RAN ·Loss of neuronal YEATS2 impairs metabolic and signaling programs, destabilizes ER Ca²⁺ homeostasis, and causes dopaminergic neuron loss with reduced TH, decreased dopamine, and locomotor deficits in YEATS2-KD flies.

Program · RAN

Neuronal Resilience, Brain Aging and Neurodegeneration

Why do some neurons cope with lifelong stress, while others fail and degenerate? In this research line, we investigate neuronal resilience as an active, molecularly encoded property that shapes brain aging and disease. We focus on how chromatin readers, energy metabolism and ER redox biology work together in vivo to determine whether neurons adapt or cross the point of no return.

Using Drosophila as a discovery platform and neuronal models for validation, we have identified YEATS-domain chromatin readers as key integrators of transcription and metabolism. Our work on YEATS2 and ENL/AF9 shows that these factors do not simply "read" histone marks, but tune mitochondrial function, stress responses and, ultimately, lifespan and neurodegeneration trajectories. In parallel, we study how ER oxidoreductases such as ERO1 couple ER and mitochondrial redox stress to neuronal vulnerability and aging. Together, these projects aim to build a mechanistic map of the pathways that keep neurons resilient — or push them towards degeneration.

Core discovery program·YEATS proteins·ER stress·Chromatin·Aging
Figure · MNDs ·Drosophila UBQLN2-ALS models show that dampening ER stress — either by ERO1 suppression or an ERO1 inhibitor — rescues eye degeneration, motor deficits and neuromuscular junction defects, illustrating our strategy of discovering ALS modifiers to elucidate disease mechanisms.

Program · MNDs

Motor Neuron Diseases

Motor neuron diseases, including ALS, sit at the intersection of RNA biology, proteostasis and metabolism. Our work in this area asks how nuclear architecture, architectural RNAs and chromatin remodeling govern the behavior of disease-linked RNA-binding proteins such as TDP-43 and FUS, and how their misregulation leads to motor neuron death.

Using Drosophila and neuronal systems, we have shown that chromatin remodelers (e.g. ISWI) and nuclear speckle RNAs (e.g. hsr-omega) actively organize the nuclear speckle environment that hosts TDP-43 and FUS. Disrupting this environment drives RBP mislocalization and disease-like post-translational modifications, placing nuclear speckles upstream of RBP pathology rather than as bystanders. On this mechanistic basis, we have built a suite of in vivo ALS models, including flies expressing the patient-derived TDP-43 G348C mutation, and we use them to dissect UBQLN2-dependent quality control, emerging roles of lipid metabolism and other modifiers of motor neuron survival. This program positions our group at the mechanistic core of how nuclear organization and proteostasis shape ALS and related disorders.

Core discovery program·ALS·TDP-43·FUS·Motor neurons·RNA biology
Figure · RareFG ·This AU-rich repeat expansion model (configured as in SCA37 and FAME) exemplifies our Drosophila transgenic pipeline, which uses site-specific pUAST-attB insertion and the UAS-GAL4 system to generate stable lines for diverse human disease genes and variants. These newly established flies show configuration-specific eye toxicity, circadian disruption, and nuclear RNA foci, and are now being used to gain mechanistic insight relevant to human repeat-expansion disorders.

Program · RareFG

Rare Diseases and Functional Genomics

Many rare neurological and neurodevelopmental disorders now have a genetic diagnosis, but the underlying mechanisms remain unclear and therapeutic options are limited. In this theme, we provide integrated in vivo and iPSC-based platforms to functionally characterize novel variants and candidate disease genes, with a particular focus on the nervous system.

The Drosophila Center for Human Diseases and Drug Discovery (DHD) hosts Thailand's first dedicated facility for generating custom transgenic fly models of human variants, enabling rapid assessment of behavioral, lifespan and neuronal phenotypes and modifier screens. In parallel, the Functional Genomics Unit (FGU) at CMUTEAM develops patient-derived iPSC models, allowing us to study neuronal differentiation, network activity and stress responses in human cells. Together with national and international clinicians and geneticists, we are building models for AU-rich repeat expansion disorders (e.g. SCA37, BAFME), NALCN-associated channelopathies, POMT1-linked movement disorders, and KBTBD13-associated neurodevelopmental disease with seizures. This theme is deliberately collaboration-driven: we invite partners to bring challenging variants, and we provide the mechanistic and functional genomics toolkit to move from genotype to mechanism.

Collaborative disease modeling platform·Rare diseases·CRISPR·iPSC·Variant interpretation
Figure · NThera ·N-Thera integrates in silico docking, human neuron assays, and Drosophila disease models to funnel compound libraries into a small number of lead neurotherapeutic candidates, illustrated here by rescue of neuromuscular junction defects in an ALS fly model after treatment with a small molecule.

Program · NThera

NeuroTherapeutic Discovery

Moving from mechanism to therapy requires experimental systems where compounds, genetic interventions and disease models can be tested side by side. In this theme, DHD and FGU work together to offer in vivo Drosophila assays and advanced in vitro neuronal/iPSC models as complementary platforms for neuroprotective discovery, compound prioritization and mechanistic drug repurposing.

On the discovery side, we have identified the pyrazolopyridine alkaloid S88 as a small molecule that mitigates neuronal ER stress and age-related functional decline, restoring ER–mitochondria homeostasis without blocking physiological stress signaling. On the repurposing side, we have demonstrated that fingolimod, approved for multiple sclerosis, can ameliorate TDP-43-driven ALS phenotypes in Drosophila, improving motor performance and reducing neurodegeneration. Building on our expertise in YEATS-domain biology, we are also evaluating selective YEATS inhibitors, originally developed for leukemia, as context-dependent modulators of neuronal stress and metabolism.

Through this theme, we collaborate with academic and clinical partners to test natural compounds, approved drugs and targeted probes in robust neurological models, aiming to identify the conditions under which specific interventions truly benefit the aging or diseased brain.

Collaborative intervention platform·Drug discovery·Drug repurposing·Neuroprotection

Open to collaborations

We actively seek partnerships with clinicians, geneticists, pharmacologists, and academic or private-sector groups whose projects benefit from integrated fly-human model pipelines.

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