Biology subjects

Vera, J. M.

Publications and source records attributed to Vera, J. M..

3 recordsLinked to original sources

bioRxiv2024

Priming versus propagating: distinct immune effects of an alpha- versus beta-particle emitting radiopharmaceutical when combined with immune checkpoint inhibition

Radiopharmaceutical therapy (RPT) enhances tumor response to immune checkpoint inhibitors (ICI) in preclinical models, but the effects of different radioisotopes have not been thoroughly compared. To evaluate mechanisms of response to RPT+ICI, we used NM600, an alkylphosphocholine selectively taken up by most tumors. Effects of 90Y-, 177Lu-, and 225Ac-NM600 + ICIs were compared in syngeneic murine models, B78 melanoma (poorly immunogenic) and MC38 colorectal cancer (immunogenic). 90Y-/177Lu-/or 225Ac-NM600 delivering 2 Gy mean tumor dose promoted tumor regression and improved survival when combined with ICIs in syngeneic mice bearing B78 or MC38 tumors. Regardless of the administered isotope, this combination was optimized with early ICI administration (days -3/0/3) relative to day 1 RPT. 90Y-NM600+ICI produced the greatest anti-tumor response for MC38, whereas high linear energy transfer (LET) alpha particle radiation from 225Ac-NM600+ICI was most effective against poorly immunogenic B78 tumors. Flow cytometry and single cell RNA and T cell receptor (TCR) sequencing illuminated distinct mechanisms of 90Y- or 177Lu-NM600 in promoting expansion of existing adaptive immunity and of 225Ac-NM600 in promoting immune priming when combined with ICI. Antitumor immune response can be achieved with appropriate application of - or {beta}- emitting RPT in combination with ICIs in diverse murine tumor models.

cancer biology↗

bioRxiv2023

Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses

Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C dominant protein loop sequences characteristic of this species capsid VP1 protein. Many of these RV-C sites were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.

immunology↗

bioRxiv2019

Heterologous glycosyl hydrolase expression and cellular reprogramming resembling sucrose-induction enable Zymomonas mobilis growth on cellobiose

Plant derived fuels and chemicals from renewable biomass have significant potential to replace reliance on petroleum and improve global carbon balance. However, plant biomass contains significant fractions of oligosaccharides that are not usable natively by many industrial microorganisms, including Escherichia coli, Saccharomyces cerevisiae, and Zymomonas mobilis. Even after chemical or enzymatic hydrolysis, some carbohydrate remains as non-metabolizable oligosaccharides (e.g., cellobiose or longer cellulose-derived oligomers), thus reducing the efficiency of conversion to useful products. To begin to address this problem for Z. mobilis, we engineered a strain (Z. mobilis GH3) that expresses a glycosyl hydrolase (GH) with {beta}-glucosidase activity from Caulobacter crescentus and subjected it to an adaptation in cellobiose medium. Growth on cellobiose was achieved after a prolonged lag phase in cellobiose medium that induced changes in gene expression and cell composition, including increased expression and secretion of GH. These changes were reversible upon growth in glucose-containing medium, meaning they did not result from genetic mutation but could be retained upon transfer of cells to fresh cellobiose medium. After adaptation to cellobiose, our GH-expressing strain was able to convert about 50% of cellobiose to glucose within 24 hours and use it for growth and ethanol production. Alternatively, pre-growth of Z. mobilis GH3 in sucrose medium enabled immediate growth on cellobiose. Proteomic analysis of cellobiose- and sucrose-adapted strains revealed upregulation of secretion-, transport-, and outer membrane-related proteins, which may aid secretion or surface display of GHs, entry of cellobiose into the periplasm, or both. Our two key findings are that Z. mobilis can be reprogrammed to grow on cellobiose as a sole carbon source and that this reprogramming is related to a natural response of Z. mobilis to sucrose that enables sucrose secretion.

microbiology↗