Publications

Association of HPV42 with digital papillary adenocarcinoma and the use of in situ hybridization for its distinction from acral hidradenoma and diagnosis at non-acral sites

Digital papillary adenocarcinoma (DPAC) is a rare tumor of sweat gland origin that preferentially affects the digits and has the potential to metastasize. Its tumor diagnosis can be difficult. Well-differentiated variants of DPAC can be confused with a benign sweat gland tumor, in particular nodular hidradenoma. With the recent detection of HPV42 DNA in DPAC by next-generation sequence analysis, we reasoned that this association could be used for diagnostic purposes.

Single-Cell Imaging Shows That the Transcriptional State of the HIV-1 Provirus and Its Reactivation Potential Depend on the Integration Site

Current antiretroviral treatment fails to cure HIV-1 infection since latent provirus resides in long-lived cellular reservoirs, rebounding whenever therapy is discontinued. The molecular mechanisms underlying HIV-1 latency are complex where the possible link between integration and transcription is poorly understood. HIV-1 integration is targeted toward active chromatin by the direct interaction with a host protein, lens epithelium-derived growth factor (LEDGF/p75).

Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation

Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers.

Dichotomous Roles of Smooth Muscle Cell-Derived MCP1 (Monocyte Chemoattractant Protein 1) in Development of Atherosclerosis

Smooth muscle cells (SMCs) in atherosclerotic plaque take on multiple nonclassical phenotypes that may affect plaque stability and, therefore, the likelihood of myocardial infarction or stroke.

ANGPTL4 influences the therapeutic response of neovascular age-related macular degeneration patients by promoting choroidal neovascularization

Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly Americans, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here we report that aqueous levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of nvAMD patients to anti-VEGF therapies.

Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

Vitiligo is an autoimmune skin disease characterized by the destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells but why white patches in stable disease persist is poorly understood. The interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools. We combine non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq) to identify subpopulations of keratinocytes in stable vitiligo patients.

Persistent cortical and white matter inflammation after therapeutic hypothermia for ischemia in near-term fetal sheep

Therapeutic hypothermia significantly improves outcomes after moderate-severe hypoxic-ischemic encephalopathy (HIE), but it is partially effective. Although hypothermia is consistently associated with reduced microgliosis, it is still unclear whether it normalizes microglial morphology and phenotype.Near-term fetal sheep (n = 24) were randomized to sham control, ischemia-normothermia, or ischemia-hypothermia.

Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome.

Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte response in the lungs of fatal COVID-19

Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines.

Genetic encoding of an esophageal motor circuit

Motor control of the striated esophagus originates in the nucleus ambiguus (nAmb), a vagal motor nucleus that also contains upper airway motor neurons and parasympathetic preganglionic neurons for the heart and lungs. We disambiguate nAmb neurons based on their genome-wide expression profiles, efferent circuitry, and ability to control esophageal muscles. Our single-cell RNA sequencing analysis predicts three molecularly distinct nAmb neuron subtypes and annotates them by subtype-specific marker genes: Crhr2, Vipr2, and Adcyap1.

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