Biology subjects

Markovitz, D. M.

Publications and source records attributed to Markovitz, D. M..

3 recordsLinked to original sources

bioRxiv2024

A genetically engineered therapeutic lectin inhibits human influenza A virus infection and sustains robust virus-specific CD8 T cell expansion

Native banana lectin (BanLec) is antiviral but highly mitogenic, which limits its therapeutic value. In contrast, the genetically engineered H84T BanLec (H84T) is not mitogenic but remains effective against influenza A virus (IAV) infection in mouse models. However, the potency and effect of H84T on human immune cells and IAV-specific immune responses is undetermined. We found that H84T efficiently inhibited IAV replication in human dendritic cells (DCs) from blood and tonsils, which preserved DC viability and allowed acquisition and presentation of viral antigen. Consequently, H84T-treated DCs initiated effective expansion of IAV-specific CD8 T cells. Furthermore, H84T preserved the capacity of IAV-exposed DCs to present a second non-IAV antigen and induce robust CD8 T cell expansion. This supports H84T as a potent antiviral in humans as it effectively inhibits IAV infection without disrupting DC function, and preserves induction of antigen-specific adaptive immune responses against diverse antigens, which likely is clinically beneficial.

immunology↗

bioRxiv2024

Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils

The intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils is not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin. We demonstrate that vimentin restricts the production of proinflammatory cytokines and reactive oxygen species (ROS), but enhances phagocytosis and swarming. We observe that vimentin is dispensable for neutrophil extracellular trap (NET) formation, degranulation, and inflammasome activation. Moreover, gene expression analysis demonstrated that the presence of vimentin was associated with changes in expression of multiple genes required for mitochondrial function and ROS overproduction. Treatment of wild-type cells with rotenone, an inhibitor for complex I of the electron transport chain, increases the ROS levels. Likewise, treatment with mitoTEMPO, a SOD mimetic, rescues the ROS production in cells lacking vimentin. Together, these data show vimentin regulates neutrophil antimicrobial functions and alters ROS levels through regulation of mitochondrial activity.

immunology↗

bioRxiv2018

The Genomic Landscape of Centromeres in Various Cancers

Centromere genomics remain poorly characterized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centromeric loci difficult to achieve. We here leverage a highly specific and targeted rapid PCR methodology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissue as compared to healthy counterparts. Quantitative reductions in select centromeric core and pericentromeric markers were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric endogenous retrovirus amplified by PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent the first look into centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression.

genomics↗