Biology subjects

Rai, A. B.

Publications and source records attributed to Rai, A. B..

3 recordsLinked to original sources

bioRxiv2026

Broad protection against Influenza A Viruses via an adjuvant-free mucosal microparticle vaccine with conserved CD8/CD4 bispecific peptides

Rapid antigenic evolution of Influenza A viruses (IAVs) enables their escape from strain-specific vaccine immunity and underscores the need for broadly protective strategies. Here, we describe a modular, adjuvant-free mucosal vaccine platform that elicits potent and cross-protective T cell immunity. The approach uses overlapping CD4+ and CD8+ epitope-dense regions from the consensus IAV M1 and NP proteins, identified through computational and functional screening. These peptides are delivered using polylactic-co-glycolic acid (PLGA) microparticles, engineered for selective uptake by antigen-presenting cells and enable sustained, pH-responsive antigen release. This design enhances antigen processing and MHC cross-presentation, functionally substituting for a conventional adjuvant. This formulation drives robust activation of primed human as well as murine CD4+ and CD8+ T cells and confers broad protection against homologous (H1N1, H3N2) as well as heterologous (H5N1) IAV strains in immunized mice. Overall, this adjuvant-free dose-sparing platform establishes an adaptable framework for next-generation broadly-protective vaccines against rapidly-evolving viruses. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/715080v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@19fafedorg.highwire.dtl.DTLVardef@d73109org.highwire.dtl.DTLVardef@1d486edorg.highwire.dtl.DTLVardef@1e663c8_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Hematopoietic stem cell conditioned media induces excessive mitochondrial fission via Drp-1 to target colorectal cancer

Mitochondria, often referred to as the "powerhouses of the cell," are particularly crucial in cancer cells due to their high energy demands. Mitochondrial fusion-fission dynamics play a critical role in regulating signaling pathways and metabolic activities in colorectal cancer (CRC) cells. Increased mitochondrial fission drives metabolic reprogramming, enabling CRCs to proliferate, metastasize, and resist chemotherapy. Paradoxically, excessive fission induces mitochondria-mediated apoptosis. Our previous studies have shown that hematopoietic stem cell-derived conditioned media (CM) modulate the apoptosis pathway and mitochondrial bioenergetics of cancer stem cells by altering the cancer microenvironment. In this study, We found that HSCs-CM facilitates excessive fission in colorectal cancer cells by modulating Drp-1 and concurrently activating the PINK1-Parkin mitophagy pathway and intrinsic apoptosis, leading to loss of viability of these cells. Moreover, proteomics data showed that HSCs-CM dysregulated the electron transport chain complexes, with an exceptionally high degree of dysregulation of complexes III and IV. Metabolomics revealed dysregulation of critical metabolites, RNA sequencing revealed dysregulation of transcripts, and proteomics revealed dysregulation of proteins, involved in mitochondrial bioenergetics and the autophagy pathway in CRCs treated with CM. Taken together, our studies reveal the therapeutic potential of HSC-conditioned media for treating colorectal cancer. HighlightsO_LIHematopoietic stem cell-derived conditioned media (HSC-CM) induces excessive mitochondrial fission in colorectal cancer (CRC) cells by upregulating Drp-1, thereby activating the intrinsic apoptotic pathway. C_LIO_LIExcessive fission and bioenergetic dysfunction caused by HSC-CM result in loss of mitochondrial membrane potential and elevated reactive oxygen species production. C_LIO_LIHSC-CM severely disrupts the electron transport chain in CRC cells, precipitating an energy crisis and engaging the PINK1-mediated mitophagy pathway. C_LI SummaryHematopoietic stem cell-derived conditioned media (HSC-CM) compromises mitochondrial dynamics by inducing excessive fission in colorectal cancer (CRC) cells through upregulation of Drp-1 and its associated protein complex. The resulting hyperfission leads to severe mitochondrial dysfunction, characterised by a loss of mitochondrial membrane potential, decreased ATP production, and disrupted electron transport chain complexes. This bioenergetic crisis and overproduction of reactive oxygen species ultimately trigger intrinsic apoptosis and engage the mitophagy pathway, leading to loss of CRC cell viability.

cancer biology↗

bioRxiv2024

PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum

Malaria parasite transits through distinct developmental stages during its life cycle in the human and mosquito host, which includes unique asynchronous division in the erythrocytes. The switch from its asexual stage to sexual forms, which is critical for disease transmission, is intricately regulated but signalling pathways involved in this process have remained unknown. In the present study, we report a novel signalling pathway involving Protein Phosphatase PfPPM2, which regulates asexual division of the parasite as well as its conversion to sexual forms. Phosphoproteomics revealed that PfPPM2 may regulate the phosphorylation of key proteins involved in chromatin remodelling and protein translation. One of the key PfPPM2-targets that emerged from these studies was Heterochromatin Protein 1 (HP1), a regulator of heritable gene silencing which contributes to both mitotic proliferation as well as sexual commitment of the parasite. We demonstrate that PfPPM2 promotes sexual conversion by regulating the interaction between HP1, H3K9me3 and chromatin and it achieves this by dephosphorylating S33 of HP1. Regulation of HP1 and Histone H3 by PfPPM2 may also contribute to division. In addition, PfPPM2 also regulates protein synthesis in the parasite by repressing the phosphorylation of initiation factor eIF2, which is likely to contribute to parasite division and possibly sexual differentiation.

microbiology↗