Publications

Objectives: We recently observed that Transient Receptor Potential V2 knockout (TRPV2 KO) mice show late-onset fetal growth restriction and perinatal lethality, which are most severe on a C57BL6 compared to 129Sv background. In the placenta of both strains, TRPV2 expression is confined to the labyrinth zone (Lz). Here, we investigated whether there were strain-specific alterations in placental morphology and nutrient transport that may underlie the difference in fetal outcomes due to TRPV2 KO. Methods: The cellular expression of TRPV2 was assessed in wildtype placentas using RNAscope.

Recent research has indicated the adult liver Sox9+ cells located in the portal triads contribute to the physiological maintenance of liver mass and injury repair. However, the physiology and pathology regulation mechanisms of adult liver Sox9+ cells remain unknown. Here, PPARα and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs.

Coincident with the start of the COVID-19 pandemic, dermatologists worldwide have reported an uncharacteristic increase in pernio or chilblains (aka ‘COVID toes’). However, the lack of systemic illness, low PCR positivity and lack of consistent seroconversion have led some authors to postulate an epiphenomenon. SARS-CoV-2 spike protein has been identified in a limited number of skin biopsies in few publications, yet there remain conflicting reports regarding other SARS-CoV-2 associated proteins, the presence or absence of viral RNA, and a unifying pathophysiology.

Pruritus is a common symptom of dermatological disorders and has a major negative impact of quality of life. Previously, it was suggested that skin derived β-defensin peptides elicit itch through activation of mast cells. Here we investigated, in more detail, the mechanisms by which β-defensins induce itch by defining the receptors activated by these peptides in humans and mice, by establishing their action in vivo, and examining their expression in dermal diseases. We found in psoriasis and atopic dermatitis, elevated expression of DEFB103 is highly correlated with skin lesions.

Single-nucleus RNA sequencing allows the profiling of gene expression in isolated nuclei. Here, we describe a step-by-step protocol optimized for adult mouse skeletal muscles. This protocol provides two main advantages compared to the widely used single-cell protocol. First, it allows us to sequence the myonuclei of the multinucleated myofibers. Second, it circumvents the cell-dissociation-induced transcriptional modifications. For complete details on the use and execution of this protocol, please refer to Dos Santos et al. (2020) and Machado, Geara et al. (2021).

The pro-inflammatory role of interleukin-6 (IL-6) is well-characterized. Blockade of IL-6, by Tocilizumab, is used in patients with rheumatoid arthritis and those diagnosed with cytokine storm. However, brain-produced IL-6 has recently emerged as a critical mediator of gut/adipose communication with the brain. Central nervous system (CNS) IL-6 is engaged by peripheral and central signals regulating energy homeostasis. IL-6 is critical for mediating hypophagia and weight loss effects of a GLP-1 analog, exendin-4, a clinically utilized drug.

Abundant evidence supports the presence of at least three distinct types of thalamocortical (TC) neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex (V1). Different types of TC neurons in mice, humans, and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex.

The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle.

Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control.

To replace one-size-fits-all cancer immunotherapy with personalized treatment, biomarkers of response and resistance as well as assays to evaluate them in each patient are essential. Among likely determinants of response, the spatial locations and activation states of the immune infiltrate appear critical. Current clinical methods for tissue analysis such as immunohistochemistry are poorly matched to the heterogeneity of the tumor immune microenvironment (TIME).