Biology subjects

Tran, J. T.

Publications and source records attributed to Tran, J. T..

4 recordsLinked to original sources

bioRxiv2025

DIA-PASEF Proteomic Profiling Reveals MpkA-Dependent Iron Stress Responses and Siderophore Biosynthesis in Aspergillus nidulans

Filamentous faungi play essential roles in biotechnology as producers of valuable bioproducts and, conversely, as opportunistic pathogens. Aspergillus nidulans is a widely used model organism for fungal genetics and cell biology; however, comprehensive proteomic references for this species remain limited. In this study, we applied a data-independent acquisition-parallel accumulation serial fragmentation (DIA-PASEF) approach to enable efficient and in-depth proteome profiling of A. nidulans. Leveraging ion mobility-based ion cloud information from DDA-PASEF experiments, we developed DIA-PASEF methods that identified 3,904 proteins across biological triplicates grown in rich medium. Compared to prior studies, this represents an increase in protein identifications of more than 140% and was achieved with more than five-fold reduction in analysis time. We employed this newly developed DIA-PASEF methodology to conduct both proteomic and phosphoproteomic analyses under iron-depleted conditions in an MpkA protein-kinase deficient mutant ({Delta}mpkA). The {Delta}mpkA strain exhibited expression of approximately 500 additional proteins and occupancy of over 1,800 additional phosphosites relative to a control. Differentially expressed and phosphorylated proteins increased by more than an order of magnitude in the {Delta}mpkA mutant across both iron-replete and iron-deplete conditions. Gene Ontology (GO) enrichment analysis revealed broader and distinct biological processes under iron-depleted conditions, highlighting adaptive responses specific to iron limitation and MAPK pathway disruption. This work establishes a high-coverage proteomic resource for A. nidulans and provides novel insights into fungal stress responses and signaling network perturbation. Importantly, high-throughput proteomic profiling reveals that limited iron availability and MAPK pathway disruption increases siderophore biosynthesis.

systems biology↗

bioRxiv2025

Lack of Bcl6 promotes anti-tumor immunity by activating glycolysis to rescue CD8 T cell function

T cells are one of the most powerful weapons to fight cancer; however, T cell exhaustion and dysfunction restrict their long-lasting function in anti-tumor immunity. B-cell lymphoma 6 (BCL6) has many functions in CD8 T cells but it is unclear how it regulates the effector function and exhaustion of CD8 cells. Overall, a low level of BCL6 mRNA in human cancer samples is associated with better outcomes. We found that BCL6 deficiency in activated CD8 T cells enhanced tumor repression in multiple mouse models. More IL-2-expressing CD8 T cells and reduced proportions of exhausted or dysfunctional CD8 T cells were detected within tumors when Bcl6 was knocked out upon T cell activation. Glycolysis was promoted in BCL6-deficient CD8 T cells owing to derepression of glucose transporter GLUT3 (encoded by Slc2a3). The BCL6 inhibitor Fx1 promoted anti-tumor immunity in a T cell-dependent manner. These findings suggest a novel pathway to restore effector function of CD8 T cells by changing their energy utilization pathways to facilitate long-term tumor resistance. Summary BlurbBCL6 limits CD8 T cell responses to tumors by inhibiting Glut3 expression. Conditional deletion of Bcl6 in activated CD8 T cells or pharmacological inhibition of BCL6 in mice represses tumor growth.

immunology↗

bioRxiv2020

Vaccine Elicitation of HIV Broadly Neutralizing Antibodies from Engineered B cells

HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against infection1. However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors and the complex maturation pathways required to generate bnAbs from these precursors2. Antibody genes can be engineered into B cells for expression as both a functional receptor on cell surfaces and as secreted antibody3-5. Here, we show that HIV bnAb-engineered primary mouse B cells can be adoptively transferred and vaccinated in immunocompetent wild-type animals resulting in the expansion of durable bnAb memory and long-lived plasma cells. Somatic hypermutation after immunization indicated that engineered cells have the capacity to respond to an evolving pathogen. These results encourage further exploration of engineered B cell vaccines as a strategy for durable elicitation of HIV bnAbs to protect against infection and as a contributor to a functional cure.

immunology↗

bioRxiv2020

B cells expressing authentic naive human VRC01-class BCRs can be primed and recruited to germinal centers in multiple independent mouse models

Animal models of human antigen-specific B cell receptors (BCR) generally depend on "inferred germline" sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three new BCR knock-in mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs). The germline-targeting HIV immunogen eOD-GT8 60mer is currently in clinical trial as a candidate bnAb vaccine priming immunogen. To attempt to model human immune responses to the eOD-GT8 60mer, we tested each authentic naive human VRC01-class BCR mouse model under rare human physiological B cell precursor frequency conditions. B cells with high (HuGL18HL) or medium (HuGL17HL) affinity BCRs were primed, recruited to germinal centers, accrued substantial somatic hypermutation, and formed memory B cells. Precursor frequency and affinity interdependently influenced responses. Taken together, these experiments utilizing authentic naive human VRC01-class BCRs validate a central tenet of germline-targeting vaccine design and extend the overall concept of the reverse vaccinology approach to vaccine development.

immunology↗