Featured Speakers
“Multiplexed Antigen-Specific Antibody Fc Profiling for Point-of-Care Diagnosis of Tuberculosis” - Sarah Ali, Ph.D. Student, Sarkar Lab
Tuberculosis (TB) is a leading cause of infectious disease related deaths despite the existence of effective treatments. Lack of accurate yet rapid and inexpensive diagnostics contributes to a significant proportion of TB deaths particularly among people living with HIV (PLHIV). Key challenges in TB diagnostics include the heterogenous spectrum of disease, ranging from latent TB infection (LTBI) to active TB (ATB), and difficulty in obtaining and processing sputum samples. Recently, we and others have observed that the inflammatory state of Mtb-specific Abs, driven by changes in Fc-glycosylation, differs across LTBI and ATB. Here, we report the discovery of a M. tuberculosis (Mtb)-specific Ab Fc profile based biomarker for TB to distinguish ATB from LTBI and a method for its point-of-care (POC) detection using an inexpensive, multiplexed and high throughput optical biosensing method.
“Epigenetic Modulation of Malignant B Cells by T cells in Lymphoid Cancers”- Lucy Britto - Ph.D. Student, Singh Lab
Abstract:
Activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive subtype of non-Hodgkins’s lymphoma associated with poor prognosis. Despite new pharmacological targets identified though molecular profiling of ABC-DLBCL, clinical trials using target therapy have not benefited these patients. To improve therapeutic strategies, immune-competent tissue models are needed to understand how DLBCL cells evade or resist treatment. This study employed synthetic hydrogel-based lymphoma organoids to illustrate how cues from the lymphoid tumor microenvironment (Ly-TME) can impact B cell receptor (BCR) signaling and tri-methylation of histone 3 at lysine 9 (H3K9me3) to dampen the effects of BCR inhibition. Using imaging techniques, we showed T cells directly increased DNA methyltransferase 3A expression and cytoskeleton formation in neighboring ABC-DLBCL cells that was regulated by H3K9me3 expression. Using expansion microscopy on lymphoma organoids captured T cell-mediated increase in the size and quantity of spatially segregated H3K9me3 clusters in proximal ABC-DLBCL cells, suggesting restructuring of high-order chromatin structures that may be associated with novel transcriptional states. Treating ABC-DLBCL cells with an inhibitor of G9α histone methyltransferase prior to inhibition of the BCR pathway protein MALT1 reversed T cell-induced H3K9me3 upregulation and mitigated T cell-mediated the dampened treatment response to BCR pathway inhibition. This study underscores the need for biologically relevant tissue models to understand how Ly-TME signals can alter DLBCL progression, spatially and temporally, and suggests targeting both aberrant signaling pathways and epigenetic cross-talk could enhance treatment efficacy for high-risk patients.
The Immunoengineering Training Seminar Series is supported by the Center for Immunoengineering at Georgia Tech.
