Biology subjects

Gipson, B.

Publications and source records attributed to Gipson, B..

3 recordsLinked to original sources

bioRxiv2025

Galectin-3 is a Nanotherapeutic Target in Graft-versus-Host Disease Mediated Kidney Injury

Kidney injury is a frequent and serious complication of allogeneic hematopoietic cell transplantation (HCT), yet its pathophysiology remains poorly understood and effective treatments are lacking. Through analysis of kidney tissue from HCT recipients, we identified substantial acute tubular injury and T cell infiltration that correlated with extra-renal graft-versus-host disease (GVHD) severity, linking systemic alloreactivity and post-transplant renal pathology. In murine models, GVHD was similarly associated with acute kidney injury, renal Th1-type T cell infiltration, and hyperactivation of NF-{kappa}B and JAK-STAT signalling. Notably, galectin-3, a damage-associated lectin, was upregulated in both patient biopsies and experimental GVHD target organs. Leveraging this pathological feature, we engineered galectin-3-targeted lipid nanoparticles for tissue-specific delivery of ruxolitinib, an approved GVHD therapy. Galectin-3 upregulation was also identified in canonical acute GVHD target organs including the liver and intestinal tract, and nanoparticle-delivered ruxolitinib substantially enhanced renal function, reduced systemic GVHD, and minimized hematologic toxicity compared to conventional drug administration. Our findings demonstrate renal involvement in acute GVHD and establish a nanoparticle-based strategy for precision delivery of immunomodulatory therapies to affected tissues.

bioengineering↗

bioRxiv2024

Sugar-rich foods exacerbate antibiotic-induced microbiome injury

Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury. One Sentence SummaryAnalyses of hematopoietic cell transplant patients and of mice uncover links between foods and microbiome disruption.

microbiology↗

bioRxiv2024

Low Kit expression identifies Hematopoietic Stem Cell subsets with enhanced lymphoid potential in mice and humans

Hematopoietic stem cells (HSCs) with multilineage potential are critical for effective T cell reconstitution and restoration of the adaptive immune system after allogeneic Hematopoietic Cell Transplantation (allo-HCT). The Kitlo subset of HSCs is enriched for multipotential precursors,1, 2 but their T-cell lineage potential has not been well-characterized. We therefore studied the thymic reconstituting and T-cell potential of Kitlo HSCs. Using a preclinical allo-HCT model, we demonstrate that Kitlo HSCs support better thymic recovery, and T-cell reconstitution resulting in improved T cell responses to infection post-HCT. Furthermore, Kitlo HSCs with augmented BM lymphopoiesis mitigate age-associated thymic alterations, thus enhancing T-cell recovery in middle-aged hosts. We find the frequency of the Kitlo subset declines with age, providing one explanation for the reduced frequency of T-competent HSCs and reduced T-lymphopoietic potential in BM precursors of aged mice.3, 4, 5 Chromatin profiling revealed that Kitlo HSCs exhibit higher activity of lymphoid-specifying transcription factors (TFs), including Zbtb1. Deletion of Zbtb1 in Kitlo HSCs diminished their T-cell potential, while reinstating Zbtb1 in megakaryocytic-biased Kithi HSCs rescued T-cell potential, in vitro and in vivo. Finally, we discover an analogous Kitlo HSC subset with enhanced lymphoid potential in human bone marrow. Our results demonstrate that Kitlo HSCs with enhanced lymphoid potential have a distinct underlying epigenetic program.

immunology↗