Browsing by Author "Md Shahadab"
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Item Genomic-microbial coevolution in human development: chromosome 2 fusion, and human accelerated regions(Springer, 2026-04-24) Singh, Siddharth; Md Shahadab; Sachin, Kumar et alHuman-specific traits arise from a confluence of genomic and ecological innovations. A unique telomere-to-telomere fusion of ancestral ape chromosomes produced human chromosome 2 (HSA2), reorganizing the genome and its regulatory landscape. In parallel, hundreds of Human Accelerated Regions (HARs), conserved elements with human-specific sequence changes, became developmental enhancers, and ancient retroviral insertions, namely, endogenous retroviruses (ERVs), were co-opted into promoters and enhancers. Here, we integrate comparative genomics, epigenomics, and host-microbiome co-evolution to propose a unified framework linking these factors to human evolution. We posit that the chromosome 2 fusion reshaped 3D genome architecture and gene regulation. HAR and endogenous retroviral sequences formed composite regulatory modules that drove innovations in cortex development, limb patterning, and immune function. Moreover, host-microbiome co-evolution is woven into this framework, with examples of microbiota-responsive HAR-ERV circuits influencing mucosal immunity, gut-brain signaling, and inflammation.Item iPSC-Derived 3D Brain Organoids as Next-generation Platforms to Study Viral and Toxicant-associated Neurodegeneration(Springer, 2026-05-12) Md Shahadab; Saini, Vaishali; Singh, Siddharth; Om Prakash; Sachin, KumarNeurodegenerative diseases (ND) are one of the most fatal diseases that affect the majority of individuals worldwide, among which Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common. In vitro 2D monolayer cell cultures and in vivo transgenic animal models have been the primary tools for investigating mechanisms of neurodegenerative diseases. However, the ineffectiveness of these models in translating outcomes into human pathophysiology, necessitates innovative approaches to bridge the translational gap. In this review, we focus on the intricate pathogenic processes by which environmental toxicants and viral infections trigger neurodegeneration. The growing significance of three-dimensional (3D) brain organoids (BOs) derived from induced pluripotent stem cells (iPSCs) can be used as a groundbreaking platform for examining neurodegenerative pathways induced by exposure to environmental toxicants and viral infections. It also addressed how BO’s overcomes the fundamental limitations of traditional models, such as 2D cultures and animal models, thereby creating novel opportunities for the mechanistic study of multifactorial neurodegeneration and the development of therapeutic interventions.
