Deepali Balasubramani
BME PhD Proposal Presentation

Date: 2025-08-04
Time: 12 PM - 2 PM
Location / Meeting Link: EBB 4029/ Zoom link: https://gatech.zoom.us/j/97138462141?pwd=dUEcBJ6uTbhSliZqQPHmuDWyaTSzuJ.1

Committee Members:
Ankur Singh, PhD (Advisor); Ahmet Coskun, PhD; Andrés García, PhD; Julia Babensee, PhD; Jean Koff, MD,MS


Title: Engineered organoids to investigate racial differences in B-cell lymphomas

Abstract:
The biology and clinical behavior of Diffuse Large B Cell Lymphoma (DLBCL) results from molecular alterations harbored by DLBCL cells and their interactions with the lymphoid tumor microenvironment (Ly-TME). Activated B cell (ABC) DLBCL, one of the more aggressive forms, depends on constitutive activation of nuclear factor κB (NF-κB) driven by B cell receptor (BCR), phosphoinositide 3-kinase (PI3K) and toll like receptor 9 (TLR9) pathways. Survival signals and external stimuli from the Ly-TME contribute to ABC DLBCL BCR signaling and progression. Transcriptomic and spatial analysis reveal unique multicellular ecosystems within the Ly-TME, associated with distinct biological and clinical behaviors. Studies investigating disparities in lymphoma outcomes have identified African American patients with inferior 5-year overall survival, diagnosis age >10 years younger than other racial groups and distinct mutational profiles indicating different oncogenic mechanisms. There is a critical gap in understanding the Ly-TME in AA ABC DLBCL versus non-Hispanic white ABC DLBCL, and how race-specific TME affects BCR signaling and NF-κB activation, influencing DLBCL progression and worse clinical outcomes. To this, the goals of my PhD dissertation is to characterize the ABC DLBCL lymphoid tumor microenvironment (Ly-TME) in African American (AA) and non-Hispanic white (NHW) patients using tissue-based cyclic immunofluorescence (t-CyCIF). Using a modular PEG-4-MAL hydrogel platform, we will engineer organoids that mimic key Ly-TME features to study ABC DLBCL progression and therapeutic responses—particularly in AA patient prevalent mutant backgrounds. We will also develop and validate AA- patient-derived organoids (PDOs) that sustain primary lymphoma cells, preserve patient heterogeneity, and predict therapeutic responses.