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Mantrala, S. K.

Publications and source records attributed to Mantrala, S. K..

2 recordsLinked to original sources

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↗

Longitudinal multi-omic profiling uncovers immune escape and predictors of response in multiple myeloma

Multiple myeloma (MM) is an incurable malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment. To investigate immune factors driving treatment response and resistance, we conducted multi-omics profiling including CD138neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138pos bulk RNA and whole-genome sequencing from 209 samples. Longitudinal analyses revealed that interferon gamma signaling impairs T cell memory after autologous stem cell transplant, while naive B cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48, p = 2.3e-4). At disease progression, MM cells upregulated cancer-testis antigens and immune effector genes, with concurrent B cell depletion, enrichment of myeloid-derived suppressor cell genes in monocytes, and T cell exhaustion. These findings highlight dynamic immune-tumor interactions, identifying naive B cell reconstitution as a biomarker of durable response, and cancer-testis antigens as potential targets for high-risk disease at progression. Statement of SignificanceLongitudinal profiling of multiple myeloma and the immune microenvironment revealed dynamic immune-tumor interactions across the disease course. Dysfunctional CD8 T cells limited memory formation post-transplant, while naive B recovery associated with sustained treatment response. At progression, cancer-testis antigen expression associated with immunosuppression, revealing novel mechanisms of immune escape.

cancer biology↗