Biomedical subjects

Chandrima Das

Publications and source records attributed to Chandrima Das.

3 recordsLinked to original sources

PubMed2026

Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.

Once identified primarily as a bioenergetic organelle, the mitochondrion has now emerged as a pivotal signalling hub that communicates with the nucleus to shape cellular fate. It integrates the cell's metabolic state with transcriptional and epigenetic programs, tweaking gene expression. Mitochondrial metabolites serve as regulators of cellular physiology, functioning as important signalling intermediates and modulating enzymes involved in epigenetic modifications. In parallel, nuclear transcriptional programs govern mitochondrial biogenesis, dynamics and quality control to preserve metabolic homeostasis under stress. Moreover, circulating metabolites can function as systemic messengers coordinating interorgan crosstalk and immune responses. Perturbations in this dynamic reciprocity can rewire the cellular script and spiral into "epimetabopathies", where metabolic-epigenetic conflicts ignite pathological conditions. This review discusses how mitochondria-nucleus crosstalk coordinates genome surveillance, metabolite-driven epigenetic regulation and systemic metabolic signalling. It further offers an overview of epimetabopathies with potential implications for future diagnostics and therapeutics.

Humans↗

PubMed2026

Epigenetic regulation of fatty acid chain elongation in MAFLD and its implications in the liver-brain axis dysfunction.

Lipid metabolism plays a crucial role in cellular health and physiology by acting as an energy storehouse, cell membrane component, brain development and signaling molecules. Crucial steps to metabolize dietary fat take place within the hepatic tissue. Any abnormalities in the hepatic fatty metabolic pathways cause abnormal accumulation of lipid inside the liver, causing MAFLD, ranging from simple steatosis to more complex steatohepatitis and fibrosis. During high-fat-diet-induced hepatic inflammation, systemic proinflammatory cytokines disrupt the blood-brain barrier, resulting in neuroinflammation, cognitive impairment, brain damage and even neurodegeneration. Further, during this altered metabolic scenario, circulating metabolites pass through the impaired BBR and deregulate the epigenetic landscape of the central nervous system. Thus, it becomes crucial to understand the epi-metabolic crosstalk between two crucial organs of our body: the liver and the brain. Here in this chapter, we demonstrate the approach that we are using in our laboratory to study the epigenetic reprogramming in the context of metabolic gene expression in the liver, which is the causal for life style disorders like MAFLD. Remarkably, we intend to understand how liver dysfunction can have an implication in the brain function. Here, we discuss the concept of developing a diet-induced steatosis and steatohepatitis mouse model to understand the disease progression and its interconnection with brain physiology. Further, we also demonstrate 2D and 3D cell culture models to study the liver-brain cross-talk in greater molecular detail. Collectively, these approaches can provide a template for studying the role of epi-metabolic cross-talk in liver-guided brain dysfunction upon MAFLD.

Animals↗

PubMed2026

The chromatin reader ZMYND8 recruits the NuRD component GATAD2A through its MYND domain to regulate MAPT213 long noncoding RNA transcription.

The zinc finger MYND-type containing eight protein (ZMYND8) is a chromatin reader that regulates neuronal gene expression by controlling the microtubule-associated protein tau (MAPT) locus. Here, we investigate how ZMYND8 regulates expression of the long non-coding RNA MAPT213 through its interaction with GATA zinc finger domain containing 2A (GATAD2A), a component of the Nucleosome Remodelling and Deacetylase complex. ZMYND8 exhibits opposite regulatory effects on protein-coding MAPT and non-coding MAPT213 transcripts in a manner dependent on its MYND domain, promoting MAPT expression while suppressing MAPT213 levels. Chromatin immunoprecipitation experiments demonstrated that ZMYND8 specifically recruits GATAD2A to the MAPT213 internal regulatory region, establishing a direct link between protein binding and transcriptional control. We determined the crystal structure of the ZMYND8 coiled-coil MYND domain at high resolution, revealing a homodimeric architecture. The MYND domain specifically recognizes GATAD2A through direct interaction with proline-rich motifs in GATAD2A's central region. Structure-function analysis identified critical binding interface residues, while quantitative measurements revealed moderate-affinity interactions enhanced through multivalent binding mechanisms. These findings establish the molecular basis for ZMYND8-mediated recruitment of chromatin remodeling complexes to specific genomic loci and provide a structural framework for understanding transcriptional regulation of MAPT213.

Humans↗