Audrey L. Smith
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View article: Figure 6 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 6 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Antibiotic-mediated microflora ablation delays CLL development, fostering a similar dysbiotic microbiome. A, WT B6 mice were randomly assigned to either receive an antibiotic cocktail (Abx) or normal drinking water (water). Five days befor…
View article: Supplementary Figure S4 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S4 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S4. Evidence of intestinal barrier disturbances in Eµ-TCL1 mice with advanced disease.
View article: Figure 7 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 7 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Compositional analysis of microbial communities following antibiotic ablation. A, LEfSe analysis demonstrating enrichment of specific bacterial taxa at the phylum level in antibiotic-receiving (Abx) leukemic mice and water-receiving (water…
View article: Figure 2 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 2 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Compositional analysis of microbial communities as CLL disease progresses. A, LEfSe analysis demonstrating enrichment of specific bacterial taxa at the phylum level in transgenic Eμ-TCL1 mice (n = 12) and WT B6 mice (n = 10) at 12 months o…
View article: Figure 5 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 5 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Dysbiotic microbiome is observed in the aggressive syngeneic model of CLL. A, Study schematic illustrating WT B6 mice were engrafted intravenously via the tail vein with 1e7 spleen-derived lymphocytes from a moribund Eμ-TCL1 mouse (CLL eng…
View article: Data from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Data from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
The gut microbiome’s role in the pathogenesis of hematologic malignancies is actively being explored; yet studies on chronic lymphocytic leukemia (CLL) are limited. Using the Eμ-TCL1 murine model of CLL, we identify a unique and dysbiotic …
View article: Supplementary Figure S6 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S6 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S6. Splenic myeloid cell populations in antibiotic-receiving leukemic mice versus water-receiving leukemic mice.
View article: Figure 4 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 4 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Differential expression of markers pertaining to intestinal integrity and inflammation in WT B6 and Eμ-TCL1 mice. ELISA was used to assess the concentration of tight junction markers in plasma of 12-month-old WT B6 and Eμ-TCL1 mice: CLDN2 …
View article: Figure 1 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 1 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
CLL alters gut bacterial diversity and generates a dysbiotic microbiome compared with WT. A, Study schematic illustrating transgenic Eμ-TCL1 and WT B6 mice were monitored with serial blood and fecal pellet sample collection over 12 months.…
View article: Supplementary Methods from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Methods from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Supplementary Materials and Methods
View article: Supplementary Figure S3 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S3 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S3. Histopathological analysis of the intestinal tract of Eµ-TCL1 mice with advanced CLL disease.
View article: Supplementary Figure S2 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S2 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S2. Relative abundance of microbiota in Eµ-TCL1 mice versus WT B6 mice.
View article: Supplementary Figure S7 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S7 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S7. Relative abundance of microbiota in antibiotic-receiving leukemic mice vs. water-receiving leukemic mice.
View article: Supplementary Figure S5 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S5 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S5. Antibiotic-mediated gut microflora ablation alters T-cell function in leukemic mice.
View article: Figure 3 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Figure 3 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Disturbances in the intestinal tract of Eμ-TCL1 mice with advanced CLL disease. A, Representative hematoxylin and eosin images of small intestine tissue in WT B6 and Eμ-TCL1 mice at 12 months (n = 7–13 mice/genotype). Hematoxylin and eosin…
View article: Supplementary Figure S1 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Supplementary Figure S1 from Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
Figure S1. Confirmation of continuous antibiotic delivery in the antibiotic-mediated gut microflora ablation model.
View article: Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia
Gut Microbiome Profiling in Eμ-TCL1 Mice Reveals Intestinal Changes and a Dysbiotic Signature Specific to Chronic Lymphocytic Leukemia Open
The gut microbiome’s role in the pathogenesis of hematologic malignancies is actively being explored; yet studies on chronic lymphocytic leukemia (CLL) are limited. Using the Eμ-TCL1 murine model of CLL, we identify a unique and dysbiotic …
View article: BET Protein Inhibition Relieves MDSC-Mediated Immune Suppression in Chronic Lymphocytic Leukemia
BET Protein Inhibition Relieves MDSC-Mediated Immune Suppression in Chronic Lymphocytic Leukemia Open
Background: Myeloid-derived suppressor cells (MDSCs) contribute to immune suppression observed in chronic lymphocytic leukemia (CLL). MDSCs are immature myeloid cells that are hijacked during development and further reprogrammed by the tum…
View article: The Elevation and Impact of Peripheral Bile Acids in Chronic Lymphocytic Leukemia
The Elevation and Impact of Peripheral Bile Acids in Chronic Lymphocytic Leukemia Open
Background: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western world. Targeted therapies have made CLL manageable for many patients, but the ongoing threat of disease relapse or transformation beckons a …
View article: Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome
Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome Open
This study reveals WM deficits as a hallmark in children with AS, demonstrating for the first time that these deficits are already apparent at 1 year of age. Parallel studies in a mouse model of AS show these deficits occur alongside the d…
View article: Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3
Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3 Open
Background: Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line…
View article: Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain
Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain Open
Transcription factor 4 (TCF4) has been implicated in a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. Mutations or deletions in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare…
View article: Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain
Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain Open
Transcription factor 4 (TCF4) has been implicated in a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. Mutations or deletions in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare…
View article: The Novel Anti-Cancer Agent, SpiD3, Is Cytotoxic in CLL Cells Resistant to Ibrutinib or Venetoclax
The Novel Anti-Cancer Agent, SpiD3, Is Cytotoxic in CLL Cells Resistant to Ibrutinib or Venetoclax Open
Background: B-cell receptor (BCR) signaling is a central driver in chronic lymphocytic leukemia (CLL), along with the activation of pro-survival pathways (e.g., NF-κB) and aberrant anti-apoptotic mechanisms (e.g., BCL2) culminating to CLL …
View article: FIGURE 6 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects
FIGURE 6 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects Open
SpiD3 prodrug (SpiD3_AP) displays antileukemic activity in Eµ-TCL1 mice. A, Synthesis of SpiD3_AP. Reagents and conditions (a) dimethyl amine (2 mol/L in MeOH), MeOH: DCM (2:1), 0°C. B, Spleen-derived malignant B cells from terminally dise…
View article: FIGURE 1 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects
FIGURE 1 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects Open
SpiD3 inhibits proliferation and induces apoptosis in malignant B cells. A, Chemical structures of analog 19 (monomer), SpiD3 and SpiD7 (dimers of analog 19). Full synthesis details reported elsewhere. B, Mitochondrial activity of CLL cell…
View article: Figure S2 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects
Figure S2 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects Open
Figure S2 shows the RNA-sequencing analysis of SpiD3-treated OSU-CLL cells.
View article: Figure S2 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects
Figure S2 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects Open
Figure S2 shows the RNA-sequencing analysis of SpiD3-treated OSU-CLL cells.
View article: FIGURE 5 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects
FIGURE 5 from Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects Open
SpiD3 synergizes with ibrutinib and elicits cytotoxic effects in ibrutinib-resistant CLL cells. A–D, Combination assays to test synergy between SpiD3 and ibrutinib (IBR; BTK inhibitor) in preclinical CLL models. HG-3 cells (A–B; n = 3 inde…