Biology subjects

Balakrishnan, B.

Publications and source records attributed to Balakrishnan, B..

5 recordsLinked to original sources

bioRxiv2026

Microsurgical Isolation and Molecular Characterization of the Mouse Left Internal Mammary Artery: Insights into Natural Resistance to Atherosclerosis

Atherosclerosis develops unevenly across the vascular tree, yet the molecular basis for this regional susceptibility remains poorly defined. The left internal mammary artery (LIMA), the most durable conduit for coronary artery bypass (CABG) surgery, is uniquely resistant to atherosclerosis in humans; however, it has never been isolated or studied in mouse models, limiting mechanistic insight into atheroprotective pathways. Here, we establish the first method to identify and isolate the murine LIMA and generate the first transcriptomic atlas of this artery. Cross-species analyses of human and mouse LIMA reveal a conserved protective signature that distinguishes the LIMA from atheroprone vessels and uncover fundamental molecular differences that govern vascular resilience. This study presents a transformative experimental platform for dissecting the determinants of atheroprotection and identifying molecular targets to improve CABG graft performance and long-term cardiovascular outcomes.

physiology↗

bioRxiv2025

Whole-body Loss of FSP27 Impairs Cognitive Function via Disruption of Neuro-Metabolic Pathways

Fat-Specific Protein 27 (FSP27), originally identified for its role in adipocyte lipid metabolism and energy homeostasis, plays a key role in regulating lipolysis and maintaining insulin sensitivity. Beyond adipose tissue, emerging studies have uncovered its involvement in hepatic and skeletal muscle function. More recently, FSP27 has also been implicated in maintaining vascular health through its influence on endothelial signaling. Despite growing insights into FSP27s systemic functions, its involvement in the central nervous system and cognitive regulation have remained unexplored. In this study, we present the first evidence that FSP27 is a critical regulator of cognitive function. Utilizing a global FSP27 knockout (Fsp27-/-) mouse model, we demonstrate that FSP27 deficiency results in significant impairments in learning, memory retention, and spatial awareness. To elucidate the underlying molecular mechanisms, genome-wide transcriptome profiling of brain tissue from Fsp27-/- mice was performed, revealing significant (P<0.05) alterations in gene expression related to neurocognition and metabolic pathways. Notably, FSP27 deletion was associated with genomic instability (P=0.05), downregulation of genes essential for axonal transport (NES=-1.91, FDR q-value=0.21), neuronal plasticity, and brain development (NES=-1.91, FDR q-value=0.28), along with signatures of disrupted systemic metabolism and elevated stress responses (NES=1.81, FDR q-value=0.20) in the brain, the processes tightly linked to cognitive dysfunction. Collectively, these findings establish FSP27 as a molecular node connecting metabolic regulation with cognitive health and identify it as a promising target for therapeutic intervention in neurodegenerative and cognitive disorders. Significance StatementFSP27, previously known for its role in lipid metabolism, is now revealed to be a critical regulator of brain function. Our study provides the first direct evidence that FSP27 supports learning and memory by maintaining neuronal integrity and regulating neurocognitive gene networks. These findings uncover an unexpected metabolic- cognitive link and position FSP27 as a promising molecular target for therapeutic strategies aimed at preventing or treating neurodegenerative and cognitive disorders.

animal behavior and cognition↗

bioRxiv2022

Surface-modified measles vaccines encoding oligomeric, fusion-stabilized SARS-CoV-2 spike glycoproteins bypass measles seropositivity, boosting neutralizing antibody responses to omicron and historical variants.

Serum titers of SARS-CoV-2 neutralizing antibodies (nAb) correlate well with protection from symptomatic COVID-19, but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are life-long after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We therefore sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated potent induction of high titer nAb in measles-immune mice and confirmed the significant incremental contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin-display of the SARS-CoV-2 spike glycoprotein, and vaccine resurfacing. In animals primed and boosted with a MeV vaccine encoding the ancestral SARS-CoV-2 spike, high titer nAb responses against ancestral virus strains were only weakly cross-reactive with the omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the omicron BA.1 spike, antibody titers to both ancestral and omicron strains were robustly elevated and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that antigen engineering can enable the development of potent measles-based SARS-CoV-2 vaccine candidates.

microbiology↗

bioRxiv2021

Boosting of SARS-CoV-2 immunity in nonhuman primates using an oral rhabdoviral vaccine

An orally active vaccine capable of boosting SARS-CoV-2 immune responses in previously infected or vaccinated individuals would help efforts to achieve and sustain herd immunity. Unlike mRNA-loaded lipid nanoparticles and recombinant replication-defective adenoviruses, replicating vesicular stomatitis viruses with SARS-CoV-2 spike glycoproteins (VSV-SARS2) were poorly immunogenic after intramuscular administration in clinical trials. Here, by G protein trans-complementation, we generated VSV-SARS2(+G) virions with expanded target cell tropism. Compared to parental VSV-SARS2, G-supplemented viruses were orally active in virus-naive and vaccine-primed cynomolgus macaques, powerfully boosting SARS-CoV-2 neutralizing antibody titers. Clinical testing of this oral VSV-SARS2(+G) vaccine is planned.

immunology↗

bioRxiv2021

Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules

Coronaviruses (CoV) exploits the endoplasmic reticulum (ER) of the host cells for replication and in doing so, increases ER stress. evokes Unfolded Protein Response (UPR) and possibly autophagy, which could all attribute to the pathophysiology of the viral infections. To date, little is known about the roles of ER stress, UPR, and autophagy in SARS-CoV-2 infection. Here we over-expressed the viral Spike (S) protein in cultured HEK293T cells, as it has been shown that such protein is largely responsible for UPR activation in other CoV-infected cells. We noticed, in the transfected cells, heightened ER stress, activation of the PERK-eIF2 arm of the UPR, induction of autophagy and cell death. When we treated the transfected cells with Tauroursodeoxycholic acid (TUDCA), 4-phenyl butyric acid (PBA), Salubrinal, Trazadone hydrochloride, and Dibenzoylmethane (DBM), we saw reduced the BiP/GRP78 levels, but only PBA and TUDCA could significantly diminish the levels of peIF2 and autophagy expression.

biochemistry↗