Publications by authors named "Kulis M"

The histone H3 at lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome-wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling.

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Background: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice.

Objective: This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice.

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Background: Sialic acid-binding immunoglobulin-like lectin-3 (Siglec-3 [CD33]) is a major Siglec expressed on human mast cells and basophils; engagement of CD33 leads to inhibition of cellular signaling via immunoreceptor tyrosine-based inhibitory motifs.

Objective: We sought to inhibit human basophil degranulation by simultaneously recruiting inhibitory CD33 to the IgE-FcεRI complex by using monoclonal anti-IgE directly conjugated to CD33 ligand (CD33L).

Methods: Direct and indirect basophil activation tests (BATs) were used to assess both antigen-specific (peanut) and antigen-nonspecific (polyclonal anti-IgE) stimulation.

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Article Synopsis
  • A clinical trial tested the effectiveness and safety of omalizumab, an anti-IgE antibody, for treating multiple food allergies in individuals aged 1 to 55, primarily focusing on its ability to allow safe consumption of peanuts and other allergic foods.
  • Out of 462 people screened, 177 children and adolescents completed the study, with 67% of those on omalizumab successfully consuming 600 mg of peanut protein without severe reactions, compared to only 7% of the placebo group.
  • The results showed similar success rates for other allergenic foods (cashew, milk, and egg), with overall safety profiles being comparable, though more injection-site reactions were reported in those receiving omalizumab.
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Unlabelled: The histone H3K27 demethylase KDM6A is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling.

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Article Synopsis
  • Palatine tonsils act as primary defenders in our immune system against diseases we inhale or ingest, and researchers created a detailed map of the human tonsil, analyzing over 556,000 cells using various techniques.
  • They discovered 121 distinct cell types, traced their development, and outlined how different immune functions are organized within the tonsils.
  • The study's findings included identifying specific cell subtypes and regulatory factors, validating their results with age-related changes, and connecting the findings to understanding certain lymphomas, enhancing our knowledge of immune responses.
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Background: Oral immunotherapy (OIT) with peanut () allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants.

Objective: Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants ( = 20) enrolled in phase 3 PTAH OIT clinical trials.

Methods: Pre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays.

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Introduction: The main objective of the study will be to evaluate the effects of two widely used standardized mindfulness-based programs [Mindfulness-Based Stress Reduction (MBSR) and Compassion Cultivation Training (CCT)], on epigenetic, neurobiological, psychological, and physiological variables.

Methods: The programs will be offered in an intensive retreat format in a general population sample of healthy volunteer adults. During a 7-day retreat, participants will receive MBSR and CCT in a crossover design where participants complete both programs in random order.

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Article Synopsis
  • Mantle cell lymphoma (MCL) shows diverse clinical and biological characteristics, complicating therapy choices, especially for older patients.
  • In a study of patients aged 60 and older treated with bendamustine and rituximab, key prognostic indicators included the simplified MCL international prognostic index (s-MIPI), MCL35 score, and blastoid cytology, which correlated with survival outcomes.
  • Combining robust proliferation assays like MCL35 with cytological evaluations and MIPI could help better classify and manage the risks of older MCL patients in future clinical trials.
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Background: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation.

Objective: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children.

Methods: Peanut-allergic 1- to 4-year-old children were randomized to receive 4 mg peanut SLIT versus placebo.

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Background: Environmental exposure to peanut through non-oral routes is a risk factor for peanut allergy. Early-life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model.

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Background: Eosinophilic esophagitis (EoE) is an immune-mediated disease, characterized by Th2-type inflammation linked to specific foods. No currently available allergy tests reliably identify food triggers in EoE, leading to empiric dietary elimination strategies. Recently, milk- and wheat-specific IgA in esophageal brushings were linked to clinical food triggers.

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Background: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, unlike C3H/HeJ (C3H) mice.

Objective: To determine the genetic basis of orally-induced anaphylaxis to peanut in CC027 mice.

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Food allergies are a growing public health problem with recent estimates of 10% of the US population affected by this immunologic disease. The quality of life is greatly impaired in food allergic individuals and their caregivers due to constant vigilance and fear of accidental exposure. Shellfish allergies are of particular concern because their prevalence has increased over the past 15 years, now affecting an estimated 3% of the adult population and 1.

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Scope: The unstructured region of Ara h 2, referred to as epitope 3, contains a repeated motif, DYPSh (h = hydroxyproline) that is important for IgE binding.

Methods And Results: IgE binding assays to 20mer and shorter peptides of epitope 3, defines a 16mer core sequence containing one copy of the DPYSh motif, DEDSYERDPYShSQDP. This study performs alanine scanning of this and a related 12mer mimotope, LLDPYAhRAWTK.

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Background: Early dietary introduction of peanut has shown efficacy in clinical trials and driven pediatric recommendations for early introduction of peanut to children with heightened allergy risk worldwide. Unfortunately, tolerance is not induced in every case, and a subset of patients are allergic prior to introduction. Here we assess peanut allergic sensitization and oral tolerance in genetically diverse mouse strains.

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Background: Indoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut.

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While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1-3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non-relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS).

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Background: Studies on the efficacy of peanut sublingual immunotherapy (SLIT) are limited. The durability of desensitization after SLIT has not been well described.

Objective: We sought to evaluate the efficacy and safety of 4-mg peanut SLIT and persistence of desensitization after SLIT discontinuation.

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