Biology subjects

Misra, H.

Publications and source records attributed to Misra, H..

3 recordsLinked to original sources

bioRxiv2026

Dual-Method Immune Deconvolution Reveals Subtype-Specific PD-L1 Drivers and a lower case Greek gammaT Cell M2 Macrophage Axis in Breast Cancer

Most computational studies of the breast cancer immune microenvironment rely on a single deconvolution algorithm. Since different tools analyze different parameters, integrated information across a dataset can be missed. Here, we employed two complementary approaches, xCell and a CIBERSORT-style ssGSEA using LM22 signatures, on 1,099 PAM50-classified primary tumors from the TCGA-BRCA cohort. PD-L1 was highest in basal-like tumors (Kruskal-Wallis p < 0.001) and correlated with CD8+ T cells ({rho} = 0.65) and M1 macrophages ({rho} = 0.67) in that subtype, which fits the standard model of IFN-{gamma}-driven adaptive upregulation. In HER2-enriched cancers, PD-L1 tracked with both effector and regulatory populations simultaneously, while luminal tumors were largely immune-quiet. The most consequential finding involved {gamma}{delta} T cells and M2 macrophages: xCell showed a non-significant correlation ({rho} = 0.048, p = 0.11), whereas CIBERSORT-ssGSEA, using curated {gamma}{delta} gene signatures, produced a significant correlation ({rho}= 0.565, p < 2.2 x 10-{superscript 1}) that held across all five subtypes. A multivariate model explained 49% of PD-L1 variance (adjusted R{superscript 2} = 0.49), and Cox regression incorporating immune features gave a concordance of 0.60. These results suggest a baseline {gamma}{delta}-M2 immunosuppressive circuit in breast cancer, particularly in ER+ disease, that could be useful to set a therapeutic target.

cancer biology↗

bioRxiv2022

Characterization of DNA processing protein A (DprA) of the radiation-resistant bacterium Deinococcus radiodurans

The uptake of environmental DNA (eDNA) by certain bacteria and its integration into their genome creates genetic diversity and new phenotypes. A DNA processing protein A (DprA) is part of a multiprotein complex and facilitate natural transformation (NT) phenotype in most bacteria. The Deinococcus radiodurans, an extremely radioresistant bacterium, is efficient in N T, and its genome encodes nearly all the components of the natural competence complex. Here, we have characterized the DprA of this bacterium (DrDprA) for the known characteristics of DprA proteins in other bacteria and the mechanisms underlying its roles in the transformation of eDNA into the bacterial genome. DrDprA is found to be a unique domain organization implicating some unique functions compared with DprA of other bacteria. In vitro studies showed that the purified recombinant DrDprA binds to both ssDNA and dsDNA with nearly equal affinity and protects ssDNA from nucleolytic degradation. DrDprA showed a strong interaction with DrRecA indicating its role in RecA catalyzed functions in vivo. Mutational studies identified amino acid residues responsible for its oligomerization, interaction with DrRecA, and DNA binding characteristics of DrDprA. Further, we demonstrated that both oligomerization and DNA binding properties of DrDprA are integral to its support in DrRecA catalyzed strand exchange reaction (SER) in vitro. These results suggested that DrDprA is largely structurally conserved with DprA homologs but showed some unique structure-function features like additional domain, the same affinity to ss/ds DNA and both oligomerization and DNA binding domains collectively contribute to its support in DrRecA functions.

molecular biology↗

bioRxiv2020

WD 40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance in Deinococcus radiodurans

RqkA, a DNA damage responsive Serine / Threonine kinase is characterized for its role in DNA repair and cell division in D. radiodurans. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight {beta} propeller repeats held together via "tryptophan-docking motifs" and forming a typical velcro closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in {gamma} radiation resistance in D. radiodurans and lacked {gamma} radiation mediated activation of kinase activity in vivo. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate E. coli cells. Further, unlike wild type enzyme, the kinase activity of its WD40 mutants was not stimulated by Pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functions in vivo and thus the role of WD40 domain in the regulation of any STPK is the first time demonstrated in bacteria. ImportanceThis study highlights the importance of the WD40 domain in activity regulation and signaling activity of bacterial serine/ threonine kinase for the first time in the bacterial response to gamma radiation and DNA damage.

molecular biology↗