A5017557486- Head and Neck Surgical Oncology
- Infectious Diseases and Mycology
- Ear and Head Tumors
- Olfactory and Sensory Function Studies
- Cerebrospinal fluid and hydrocephalus
- Cancer Immunotherapy and Biomarkers
- Tumors and Oncological Cases
- Neuroblastoma Research and Treatments
- Vestibular and auditory disorders
- Glycogen Storage Diseases and Myoclonus
- Ophthalmology and Eye Disorders
- Immune cells in cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Neurogenesis and neuroplasticity mechanisms
- Salivary Gland Tumors Diagnosis and Treatment
- Advanced Chemical Sensor Technologies
- Glioma Diagnosis and Treatment
- Receptor Mechanisms and Signaling
- Nasal Surgery and Airway Studies
- Long-Term Effects of COVID-19
- Mosquito-borne diseases and control
- Polyomavirus and related diseases
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- Neuroinflammation and Neurodegeneration Mechanisms
Duke University
2020-2024
Duke University Hospital
2023
Duke Medical Center
2023
Wellcome/MRC Cambridge Stem Cell Institute
2019-2022
University of Cambridge
2019-2022
Princeton University
2016-2020
Addenbrooke's Hospital
2019
Hospital César Milstein
2016-2018
Neurological Surgery
2018
Antrim Area Hospital
2018
SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how persistent loss a subset patients. To address this question, we analyzed epithelial samples collected from 24 biopsies, nine objectively quantified long-term after...
The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish genetically engineered mouse model high-grade metastatic ONB exhibiting NEUROD1
Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor-exhausted (Tex_prog) better reflect immunotherapeutic responsivity. Here, we examined intratumoral cellular interactions that govern transition to terminal cell exhaustion. We defined a metric reflecting progenitor exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers. Single-cell analyses Tex_prog and Tex_term...
ABSTRACT. The MoCA is a brief useful test to diagnose mild cognitive impairment (MCI) and dementia (MD). To date, no Argentine cross-cultural adapted validations of the Spanish version have been reported. Objective: validate in elderly study its usefulness MCI MD. Methods: This included 399 individuals over 60 years old evaluated Cognitive-Behavioral Department (2017-2018). Patients with<3 education, sensory disturbances, psychiatric disorders, or moderate-severe were excluded. control...
Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% COVID patients lasting olfactory dysfunction. While animal studies autopsy tissues have suggested mechanisms underlying loss the pathophysiology that underlies persistent smell remains unclear. Here we combine objective measurements suffering from post-acute sequelae infection (PASC) with single cell sequencing histology epithelium (OE). This approach reveals OE harbors a diffuse...
Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult cancer, glioblastoma (GBM). We compared productive ZIKV infection HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although proved uniformly vulnerable to infection, was more refractory, this correlated with an innate immune expression signature. Indeed, GBM-derived...
Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of nasal cavity. Because low incidence this tumor, as well an absence established cell lines and murine models, understanding mechanisms driving pathobiology has been challenging. Here, we sought to apply advances research on human epithelial neurogenic niche, along with new biocomputational approaches, better understand cellular molecular factors in low- high-grade how specific transcriptomic markers may predict...
The scalable production of uniformly distributed graphene (GR)-based composite materials remains a sizable challenge. While GR-polymer nanocomposites can be manufactured at large scale, processing limitations result in poor control over the homogeneity hydrophobic GR sheets matrices. Such processes often difficulties controlling stability and avoiding aggregation, therefore eliminating benefits that might have otherwise arisen from nanoscopic dimensions GR. Here, we report an exfoliated...
The rapid onset of a bilateral vestibular hypofunction (BVH) is often attributed to ototoxicity. However, without any prior exposure ototoxins, the idiopathic form BVH most common. Although sequential neuritis (VN) described as cause BVH, clinical evidence for simultaneous and acute VN unknown. We describe patient with an severe gait ataxia oscillopsia features compatible putatively due VN, which we serially evaluated laboratory function testing over course 1 year. Initially, superior...
Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood.
Originating from the olfactory neuroepithelium, neuroblastoma is a rare malignant tumor of nasal cavity that typically affects adults between ages 35 and 70. Clinical presentation predominantly consists nonspecific symptoms such as obstruction, drainage or epistaxis, thus illustrating need for thorough diagnostic workup. In addition to complete head neck examination, rigid endoscopy, biopsy imaging are necessary establish definitive diagnosis well plan treatment. Computed tomography (CT)...
Ménière's attack has been shown to temporarily alter the vestibuloocular reflex (VOR). A patient with unilateral disease was serially evaluated video Head Impulse Test during single, untreated episodes of acute vertigo. Spontaneous nystagmus activity concurrently recorded in order establish three typical phases (irritative, paralytic, and recovery) correlate them VOR performance. The onset associated a quick change gain on side affected ear. While rapidly progressive reduction evident at...
Mesangial cells are the major extracellular matrix (ECM)-producing in kidney glomerulus and, when exposed to elevated glucose levels, they up-regulate assembly of fibronectin (FN) and other ECM proteins. Increases concentration known alter gene expression; here we investigated connection between increased production changes expression mesangial cells. Comparison grown normal or high conditions by RNA-sequencing showed significant over 6000 genes grouped KEGG pathway analysis, identified...
A 77-year-old woman diagnosed with a pontine cavernoma developed progressive difficulty swallowing. videofluoroscopic swallowing study showed low-frequency rhythmic contractions of the soft palate and upper larynx (video at [Neurology.org][1]). Brain MRI revealed hypertrophy in right inferior olivary nucleus (figure). [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000004423
Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable injury yet essential for olfaction. Multipotent basal stem cells activated by damage, although mechanisms regulating lineage decisions not understood. Using mouse lesion models, we focused on defining role Polycomb repressive complexes (PRCs) neurogenesis. PRC2 has a well-established developing tissues, orchestrating transcriptional programs via chromatin modification....
Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory epithelium. Current therapeutic approaches have not significantly changed over previous decades, and two-year survival of high grade ONB remains low at approximately 40%, partially due to an incomplete understanding biology. An absence robust pre-clinical or culture models has been barrier for development new treatment strategies. Here we sought establish in vitro patient-derived model order allow downstream...
KEY POINTS We developed a culture model of human olfactory ensheathing cell tumor. Cultured organoids resemble normal cells. Assays suggest that this provides tool for studying the roles these glial cells in maintenance peripheral system.
Abstract While terminally exhausted T cells (Tex_term) retain important anti-tumor cytotoxic function, it is the relative preservation of renewable, stem-like progenitor exhaustion (Tex_prog) that better indicates immunotherapeutic responsivity. Although restraining progression from Tex_prog to Tex_term thus takes on clinical significance, cellular interactions in a tumor microenvironment (TME) governing such remain less established. Employing glioblastoma (GBM) and other solid tumors as...
Abstract Intracranial tumors present unique challenges for immunotherapy. These can include both local and systemic modes of immune suppression, the mechanistic underpinnings which are incompletely understood. Our work reveals that intracranial elicit increases in circulating catecholamine levels, this chronic sympathetic hyperactivity results T cell dysfunction impedes immunotherapeutic efficacy. We show treatment with b-adrenergic blockade partially overcome negative impacts by increasing...
SUMMARY Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor (Tex_prog) better reflect immunotherapeutic responsivity. Here, we examined intratumoral cellular interactions that govern transition to terminal cell exhaustion. We defined a metric reflecting exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers. Single analyses Tex_prog and Tex_term glioblastoma (GBM),...