Suzanne Marie Barshow

All Publications

• EOSINOPHIL PEROXIDASE STAINING ENHANCES THE DIAGNOSTIC UTILITY OF THE CYTOSPONGE IN EOSINOPHILIC ESOPHAGITIS. Clinical and translational gastroenterology Masuda, M. Y., Barshow, S. M., Garg, S., Putikova, A., LeSuer, W. E., Alexander, J. A., Katzka, D. A., Dellon, E. S., Kita, H., Horsley-Silva, J. L., Doyle, A. D., Wright, B. L. 2022

  Abstract

  We aimed to assess the diagnostic utility of eosinophil peroxidase (EPX) staining on Cytosponge™ (CS) samples in eosinophilic esophagitis (EoE).Esophageal biopsy (BX) samples from adult EoE subjects were assessed using peak eosinophils per high-power field (eos/hpf), EPX, and the EoE Histologic Scoring System (EoEHSS). EPX staining and eos/hpf were compared (BX vs. CS).CS EPX positivity correlated with eos/hpf (CS [r=0.82, P<0.0001]; BX [r=0.65, P<0.0001]) and EoEHSS (grade [r=0.62, P<0.00001]; stage [r=0.61, P<0.0001]). CS EPX identified active EoE subjects (AUC=0.86, P<0.0001).The correlation of CS EPX with eosinophilic inflammation and histologic disease severity supports its diagnostic utility in EoE.

  View details for DOI 10.14309/ctg.0000000000000534

  View details for PubMedID 36137185

• Mechanisms of oral immunotherapy. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology Barshow, S. M., Kulis, M. D., Burks, A. W., Kim, E. H. 2021; 51 (4): 527-535

  Abstract

  Food allergy presents a significant global health concern with up to 10% of the population affected in developed nations and a steadily increasing prevalence. In many cases, particularly with peanut, tree nut and shellfish, food allergy is a lifelong and potentially life-threatening diagnosis. While no 'cure' for IgE-mediated food allergy exists, oral immunotherapy (OIT) is a promising treatment modality with the peanut OIT drug Palforzia (Aimmune Therapeutics) the only treatment for food allergy that is currently approved by the United States Food and Drug Administration. OIT primarily induces a state of desensitization with only a minority of subjects achieving sustained unresponsiveness, a state of limited clinical remission that appears to be immunologically distinct from natural tolerance. Early humoural changes during OIT include an initial increase in allergen-specific IgE, which eventually decreases to below baseline levels as OIT progresses, and a gradual increase in allergen-specific IgA and IgG4 that continues throughout the course of OIT. Basophil hyporesponsiveness and decreased skin prick test wheal size are observed within the first year of OIT, and persistence after completion of therapy has been associated with sustained unresponsiveness. In the T-cell compartment, there is an initial expansion followed by a decline in the number and activity of T helper 2 (TH 2) cells, the latter of which may be dependent on an expansion of IL-10-producing cells, including regulatory T-cells. Our understanding of the immunomodulatory effects of OIT continues to evolve, with new technologies such as single-cell transcriptional profiling and antibody epitope analysis allowing for more detailed study of T-cell and B-cell responses to OIT. In this review, we present evidence to illustrate what is currently known about the immunologic changes induced by OIT, explore potential mechanisms and emphasize knowledge gaps where future research is needed.

  View details for DOI 10.1111/cea.13824

  View details for PubMedID 33417257

  View details for PubMedCentralID PMC9362513

• Image Analysis of Eosinophil Peroxidase Immunohistochemistry for Diagnosis of Eosinophilic Esophagitis. Digestive diseases and sciences Wright, B. L., Doyle, A. D., Shim, K. P., Pai, R. K., Barshow, S. M., Horsley-Silva, J. L., Luo, H., Rank, M. A., Jacobsen, E. A., Katzka, D. A., Kita, H., Dellon, E. S. 2021; 66 (3): 775-783

  Abstract

  Diagnosis of eosinophilic esophagitis (EoE) requires manual quantification of tissue eosinophils. Eosinophil peroxidase (EPX) is an eosinophil-specific, cytoplasmic granule protein released during degranulation.The objective of this study was to evaluate image analysis of EPX immunohistochemistry as an automated method for histologic diagnosis of EoE.We performed a secondary analysis of prospectively collected esophageal biopsies obtained from adult subjects with EoE and controls. Tissue sections were stained with hematoxylin and eosin (H&E) and evaluated for peak eosinophils per high power field (eos/hpf). The same slides were de-stained and re-stained to detect EPX for direct comparison. Slides were digitized, and EPX staining area/mm2 was quantified using image analysis. Paired samples were compared for changes in EPX staining in treatment responders and non-responders.Thirty-eight EoE cases and 49 controls were analyzed. Among EoE subjects, matched post-treatment biopsies were available for 21 responders and 10 non-responders. Baseline EPX/mm2 was significantly increased in EoE subjects and decreased in treatment responders. EPX quantification correlated strongly with eos/hpf (r = 0.84, p < 0.0001) and identified EoE subjects with high diagnostic accuracy (AUC 0.95, p < 0.0001). The optimal diagnostic EPX-positive pixel/area threshold was 17,379 EPX/mm2. Several controls (5/49) with < 15 eos/hpf on H&E staining exceeded this cutoff.EPX/mm2 correlates strongly with eos/hpf, accurately identifies subjects with EoE, and decreases in treatment responders. Automated quantification of intact eosinophils and their degranulation products may enhance pathologic assessment. Future studies are needed to correlate EPX/mm2 with symptoms, endoscopic findings, and esophageal distensibility.

  View details for DOI 10.1007/s10620-020-06230-5

  View details for PubMedID 32248390

  View details for PubMedCentralID PMC7541435

• A reappraisal of mortality after epilepsy surgery. Neurology Sperling, M. R., Barshow, S., Nei, M., Asadi-Pooya, A. A. 2016; 86 (21): 1938-44

  Abstract

  To assess whether epilepsy surgery is associated with a reduction in mortality rate and if postoperative seizure frequency and severity affect mortality.A total of 1,110 patients were evaluated (1,006 surgically and 104 nonsurgically treated) for a total follow-up of 8,126.62 person-years from 1986 to 2013. Deaths were ascertained through database and Social Security Death Index query. Patients were grouped by surgery type and seizure status; standardized mortality ratio and deaths per 1,000 person-years were calculated. Survival analysis and Cox proportional hazard regression were performed.Eighty-nine deaths were observed. Surgically treated patients had a lower mortality rate (8.6 per 1,000 person-years [95% confidence interval (CI) 6.58-11.15]) than nonsurgically treated patients (25.3 per 1,000 person-years [14.50-41.17]; p < 0.001). Seizure-free patients had a lower mortality rate (5.2 per 1,000 person-years [95% CI 2.67-9.02]) than non-seizure-free patients (10.4 per 1,000 person-years [95% CI 7.67-13.89] p = 0.03). More frequent postoperative tonic-clonic seizures (>2 per year) were associated with increased mortality (p = 0.006) whereas complex partial seizure frequency was not related to death rate. Mortality was similar in temporal and extratemporal epilepsy patients (p = 0.7).Brain surgery is associated with a reduction in mortality rate in drug-resistant epilepsy, both when seizures are abolished and when it results in significant palliation of tonic-clonic seizure frequency. These observations provide further rationale for earlier consideration of epilepsy surgery.

  View details for DOI 10.1212/WNL.0000000000002700

  View details for PubMedID 27164679

• EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nature neuroscience Huang, X., He, Y., Dubuc, A. M., Hashizume, R., Zhang, W., Reimand, J., Yang, H., Wang, T. A., Stehbens, S. J., Younger, S., Barshow, S., Zhu, S., Cooper, M. K., Peacock, J., Ramaswamy, V., Garzia, L., Wu, X., Remke, M., Forester, C. M., Kim, C. C., Weiss, W. A., James, C. D., Shuman, M. A., Bader, G. D., Mueller, S., Taylor, M. D., Jan, Y. N., Jan, L. Y. 2015; 18 (9): 1236-46

  Abstract

  Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment.

  View details for DOI 10.1038/nn.4088

  View details for PubMedID 26258683

  View details for PubMedCentralID PMC4639927

• The bHLH repressor Deadpan regulates the self-renewal and specification of Drosophila larval neural stem cells independently of Notch. PloS one Zhu, S., Wildonger, J., Barshow, S., Younger, S., Huang, Y., Lee, T. 2012; 7 (10): e46724

  Abstract

  Neural stem cells (NSCs) are able to self-renew while giving rise to neurons and glia that comprise a functional nervous system. However, how NSC self-renewal is maintained is not well understood. Using the Drosophila larval NSCs called neuroblasts (NBs) as a model, we demonstrate that the Hairy and Enhancer-of-Split (Hes) family protein Deadpan (Dpn) plays important roles in NB self-renewal and specification. The loss of Dpn leads to the premature loss of NBs and truncated NB lineages, a process likely mediated by the homeobox protein Prospero (Pros). Conversely, ectopic/over-expression of Dpn promotes ectopic self-renewing divisions and maintains NB self-renewal into adulthood. In type II NBs, which generate transit amplifying intermediate neural progenitors (INPs) like mammalian NSCs, the loss of Dpn results in ectopic expression of type I NB markers Asense (Ase) and Pros before these type II NBs are lost at early larval stages. Our results also show that knockdown of Notch leads to ectopic Ase expression in type II NBs and the premature loss of type II NBs. Significantly, dpn expression is unchanged in these transformed NBs. Furthermore, the loss of Dpn does not inhibit the over-proliferation of type II NBs and immature INPs caused by over-expression of activated Notch. Our data suggest that Dpn plays important roles in maintaining NB self-renewal and specification of type II NBs in larval brains and that Dpn and Notch function independently in regulating type II NB proliferation and specification.

  View details for DOI 10.1371/journal.pone.0046724

  View details for PubMedID 23056424

  View details for PubMedCentralID PMC3466283

• Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Drosophila larval brains. Proceedings of the National Academy of Sciences of the United States of America Zhu, S., Barshow, S., Wildonger, J., Jan, L. Y., Jan, Y. N. 2011; 108 (51): 20615-20

  Abstract

  Intermediate neural progenitor (INP) cells are transient amplifying neurogenic precursor cells generated from neural stem cells. Amplification of INPs significantly increases the number of neurons and glia produced from neural stem cells. In Drosophila larval brains, INPs are produced from type II neuroblasts (NBs, Drosophila neural stem cells), which lack the proneural protein Asense (Ase) but not from Ase-expressing type I NBs. To date, little is known about how Ase is suppressed in type II NBs and how the generation of INPs is controlled. Here we show that one isoform of the Ets transcription factor Pointed (Pnt), PntP1, is specifically expressed in type II NBs, immature INPs, and newly mature INPs in type II NB lineages. Partial loss of PntP1 in genetic mosaic clones or ectopic expression of the Pnt antagonist Yan, an Ets family transcriptional repressor, results in a reduction or elimination of INPs and ectopic expression of Ase in type II NBs. Conversely, ectopic expression of PntP1 in type I NBs suppresses Ase expression the NB and induces ectopic INP-like cells in a process that depends on the activity of the tumor suppressor Brain tumor. Our findings suggest that PntP1 is both necessary and sufficient for the suppression of Ase in type II NBs and the generation of INPs in Drosophila larval brains.

  View details for DOI 10.1073/pnas.1118595109

  View details for PubMedID 22143802

  View details for PubMedCentralID PMC3251047