Publications by authors named "Catherine A A Lee"

The skin is the most immunogenic tissue in transplantation and the most difficult tissue in which to induce immune modulation. Batf3-dependent type 1 conventional dendritic cells (cDC1s) are important in initiating rejection in murine skin transplantation. In humans, the CD141 cDC1 subset is the functional counterpart of the murine Batf3-dependent cDC1s.

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Caveolin (CAV) 1 and 2 are integral membrane proteins that constitute major components of small membrane pouches termed caveolae. While several functions have been described in other tissues, the roles of CAV1 and CAV2 in the ocular surface have remained unknown. In the current study, we investigated the expression and function of CAV1 and CAV2 in the human cornea.

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  • The study investigates the immunological processes related to lymphadenopathy in facial transplant patients, focusing on how donor-derived lymph nodes contribute to these processes after vascularized composite allograft (VCA) transplantation.
  • It analyzes clinical and histological data from 9 patients, revealing that those who received donor lymph nodes developed bilateral lymphadenopathy, which resolved over time.
  • The findings indicate that an immunological response involving both donor and recipient lymphocytes occurs in the lymph nodes, suggesting a unique rejection mechanism that differs from typical skin rejection in transplant patients.*
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  • Recessive dystrophic epidermolysis bullosa (RDEB) is a serious skin condition caused by mutations in the COL7A1 gene, leading to severe skin fragility and a high risk of aggressive skin cancer (squamous cell carcinoma).
  • This study used whole-genome and RNA sequencing in a single RDEB patient to understand how their skin cancer develops and to look for new treatment options.
  • Researchers identified PLK-1 as a potential target for therapy and noted that factors like microsatellite instability and accelerated aging might increase the aggressiveness and early occurrence of the skin cancer associated with RDEB.
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  • * Traditional immune checkpoint blockade (ICB) therapies targeting the PD-(L)1 axis have been largely ineffective, prompting researchers to explore the use of epigenetic modulators for better personalized immunotherapy outcomes.
  • * A novel 3D screening platform using patient-derived tumor samples has shown that responses to chemotherapy and immunotherapy correlate with immune cell activity and tumor characteristics, suggesting that combining epigenetic priming with ICB could enhance immune response and offer more effective treatment strategies.
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  • Immune-related adverse events (irAEs) can occur during PD-1 cancer immunotherapy and need more research to understand how they compare to regular autoimmune diseases.
  • A study using single-cell RNA sequencing on mice showed that anti-PD-1 therapy caused distinct changes in T cells associated with type 1 diabetes (T1D), leading to differences in cell types and function compared to naturally occurring T1D.
  • Findings suggest that blood samples from mice treated with anti-PD-1 can be valuable for monitoring irAEs, as the T cell markers differ from those seen in spontaneous T1D, providing potential insights for patient treatment.
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  • - Vascularized composite allotransplantation (VCA) is a new surgical method that helps treat severe injuries, such as losing limbs or facial injuries, by transplanting various tissue types like skin, bone, and muscle.
  • - The body's immune system often rejects VCA grafts, especially those with skin, due to their strong antigenicity, which challenges the balance between accepting and rejecting the transplant.
  • - Recent research is uncovering the immune cells involved in graft rejection, aiming to develop targeted therapies that could improve the management of VCA transplant patients and potentially reduce the need for lifelong immunosuppression.
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  • - Vascularized composite allografts (VCAs), particularly of the face, can suffer from chronic rejection, which occurs over long periods and is not fully understood, as shown by the evaluation of a VCA removed after 88 months.
  • - The study revealed that donor-derived CD8-positive T cells infiltrate the graft's arteries, leading to damage in recipient-derived endothelial cells, contributing to arteriosclerosis.
  • - Advanced proteomic analysis identified specific proteins linked to activated T cells and macrophages along with pathways related to artery hardening, suggesting a chronic rejection mechanism driven by T cell responses and the graft's vascular environment.
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  • Epigenetic modification of DNA through 5-hydroxymethylcytosine (5hmC), produced by TET enzymes, plays a crucial role in regulating gene expression in various tissues, including the cornea of the human eye.
  • The study showed that 5hmC and the enzyme TET2 are highly expressed in mature corneal cells, and reducing TET2 led to decreased 5hmC levels and disrupted key molecular pathways that are essential for corneal differentiation.
  • These findings suggest that TET2 has a significant role in regulating gene expression in corneal epithelial cells and may offer new strategies for treating corneal diseases linked to issues with cell maturation.
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  • The research identifies a specific limbal epithelial progenitor subpopulation that is highly proliferative and marked by the expression of basal cell adhesion molecule (BCAM), crucial for corneal epithelial regeneration.
  • BCAM-positive cells exist alongside both ABCB5-positive limbal stem cells and ABCB5-negative epithelial cells, indicating a broader role in the corneal epithelium.
  • The study reveals that BCAM is essential for cellular migration and differentiation, with its expression regulated by the transcription factor p63, highlighting BCAM's importance in corneal epithelial differentiation.
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Purpose: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). While the ocular surface is considered one of the major SARS-CoV2 transmission routes, the specific cellular tropism of SARS-CoV2 is not fully understood. In the current study, we evaluated the expression and regulation of two SARS-CoV2 viral entry proteins, TMPRSS2 and ACE2, in human ocular epithelial cells and stem cells.

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Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor, has been shown to play a regulatory role in melanoma, although its function during tumor progression remains unclear. Here, we demonstrate that ATF-3 exhibits tumor suppressive function in melanoma. Specifically, ATF-3 nuclear expression was significantly diminished with melanoma progression from nevi to primary to metastatic patient melanomas, correlating low expression with poor prognosis.

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Glioblastoma multiforme (GBM) is a malignant brain tumor with a poor prognosis resulting from tumor resistance to anticancer therapy and a high recurrence rate. Compelling evidence suggests that this is driven by subpopulations of cancer stem cells (CSCs) with tumor-initiating potential. ABC subfamily B member 5 (ABCB5) has been identified as a molecular marker for distinct subsets of chemoresistant tumor-initiating cell populations in diverse human malignancies.

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Epigenetic regulation has a profound influence on stem cell fate during normal development in maintenance of physiologic tissue homeostasis. Here we report diminished ten-eleven translocation (TET) methylcytosine dioxygenase expression and loss of the DNA hydroxymethylation mark 5-hydroxymethylcytosine (5-hmC) in keratinocyte stem cells and transit amplifying cells in human psoriasis and in imiquimod-induced murine psoriasis. Loss of 5-hmC was associated with dysregulated keratinocyte stem cell kinetics, resulting in accumulation of nestin and FABP5-expressing transit amplifying cells to produce classic psoriatic epidermal architecture.

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Single-cell RNA sequencing (scRNA-seq) has been widely applied to discover new cell types by detecting sub-populations in a heterogeneous group of cells. Since scRNA-seq experiments have lower read coverage/tag counts and introduce more technical biases compared to bulk RNA-seq experiments, the limited number of sampled cells combined with the experimental biases and other dataset specific variations presents a challenge to cross-dataset analysis and discovery of relevant biological variations across multiple cell populations. In this paper, we introduce a method of variance-driven multitask clustering of single-cell RNA-seq data (scVDMC) that utilizes multiple single-cell populations from biological replicates or different samples.

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Background: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood-brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion.

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