Christopher Castaldi
A5036381485- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Fetal and Pediatric Neurological Disorders
- Long-Term Effects of COVID-19
- Cerebral Palsy and Movement Disorders
- Immunodeficiency and Autoimmune Disorders
- Blood groups and transfusion
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Metabolism and Genetic Disorders
- Platelet Disorders and Treatments
- COVID-19 epidemiological studies
- Genomics and Rare Diseases
- Autism Spectrum Disorder Research
- Epigenetics and DNA Methylation
- Cerebrospinal fluid and hydrocephalus
- Genetic and Kidney Cyst Diseases
- Evolution and Genetic Dynamics
- Hedgehog Signaling Pathway Studies
- Viral Infections and Outbreaks Research
- Cerebrovascular and genetic disorders
- Diabetes Treatment and Management
- Neurofibromatosis and Schwannoma Cases
- Intracranial Aneurysms: Treatment and Complications
Yale University
2017-2023
Yale Cancer Center
2017-2023
Broad Institute
2022
Center for Genomic Science
2022
Genetic Analysis (Norway)
2020
Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there no consensus on consequences of CNS infections. Here, we used three independent approaches probe capacity infect brain. First, using human brain organoids, observed clear evidence infection with accompanying metabolic changes in infected and neighboring neurons. However, for type I interferon responses was detected. We...
The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1-6. Here we analysed the development anti-SARS-CoV-2 antibody and T cell responses individuals who were previously infected (recovered) uninfected (naive) received mRNA vaccines to SARS-CoV-2. While sustained higher titres than post-vaccination, latter reached comparable levels neutralization ancestral strain after second vaccine...
Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there no consensus whether virus can infect brain, or what consequences of CNS infection are. Here, we used three independent approaches probe capacity brain. First, using human brain organoids, observed clear evidence with accompanying metabolic changes in infected and neighboring neurons. However, for type I interferon responses...
The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%–80% increased transmissibility over Alpha. To investigate if this ostensible difference is uniform across populations, we partner with public health programs from all six states New England the United States. We compare logistic growth rates during each variant's respective emergence period, finding that emerged 1.37–2.63 times faster than Alpha (range states). compute variant-specific effective...
Abstract Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, signatures associated with immunopathology poorly understood. Here we use multi-omics single-cell analysis to probe dynamic hospitalized patients stable or progressive course of COVID-19, explore V(D)J repertoires, and assess cellular effects tocilizumab. Coordinated profiling gene expression cell lineage protein markers shows that S100A hi /HLA-DR lo classical monocytes...
The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity lineage B.1.517 during a SARS-CoV-2 lasting 471 days (and still ongoing) with consistently recovered infectious virus high viral genome copies. During infection, find an accelerated evolutionary rate translating to 35 nucleotide...
Significance Craniosynostosis is a common congenital malformation resulting from premature fusion of the bones that comprise cranial vault, requiring surgery in infancy to prevent adverse neurologic outcomes. Eighty-five percent cases are non-syndromic and unknown cause. By exome sequencing families with midline craniosynostosis, we show 5% have de novo damaging mutations negative regulators Wnt, bone morphogenetic protein (BMP), Ras/ERK signaling pathways, developmental cascades converge on...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection reinfection. By contrast, less is known about escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated all SARS-CoV-2 VOCs ability suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral genes contribute...
Rett syndrome (RTT) and epileptic encephalopathy (EE) are devastating neurodevelopmental disorders with distinct diagnostic criteria. However, highly heterogeneous overlapping clinical features often allocate patients into the boundary of two conditions, complicating accurate diagnosis appropriate medical interventions. Therefore, we investigated specific molecular mechanism that allows an understanding pathogenesis relationship these conditions.We screened novel genetic factors from 34...
<h3>Importance</h3> Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is cause childhood stroke. The MMD poorly understood, but genetic factors play role. Several familial forms have been identified, most cases remains elusive, especially among non–East Asian individuals. <h3>Objective</h3> To assess whether ultrarare de novo rare, damaging transmitted variants with large effect sizes are associated...
Abstract Effectively monitoring the spread of SARS-CoV-2 mutants is essential to efforts counter ongoing pandemic. Predicting lineage abundance from wastewater, however, technically challenging. We show that by sequencing RNA in wastewater and applying algorithms initially used for transcriptome quantification, we can estimate samples. find high variability signal among individual samples, but overall trends match those observed clinical Thus, while remains a more sensitive technique...
The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity lineage B.1.517 during a lasting 471 days (and still ongoing) with consistently recovered infectious virus high viral loads. During infection, found an accelerated evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than global rate. This led...
Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play role in disease pathogenesis. However, no unbiased, large-scale genomic study has been performed date. Analysis 290 whole exome-sequenced probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment rare, damaging variants GABA receptor-binding genes cases. Mice engineered with...
The emergence of the B.1.617.2 (Delta) variant SARS-CoV-2 has led to increases in both infections and hospitalizations among adolescents. Little is known about effectiveness BNT162b2 vaccine adolescents general population, as opposed a clinical trial population.To estimate aged 12 18 years.This was matched case-control study (aged 12-18 years) who had results from reverse transcription-polymerase chain reaction (RT-PCR) test. Immunization histories, relevant data, RT-PCR test were obtained...
Abstract A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, molecular and cellular mechanisms by which causes lethal immunopathology are poorly understood. Here, we utilize multiomics single-cell analysis to probe dynamic responses patients with stable or progressive manifestations of COVID-19, assess effects tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling gene expression cell lineage protein markers...
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to shape the disease 2019 (Covid-19) pandemic. detection and rapid spread SARS-CoV-2 ‘ Omicron’ variant (lineage B.1.1.529) in Botswana South Africa became a global concern because it contained 15 mutations spike protein immunogenic receptor binding domain was less neutralized by sera derived from vaccinees compared previously dominant Delta variant. To investigate if Omicron is more...
The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used different countries, although data comparing their efficiency improving protective immunity remain sparse, especially among vulnerable populations, including older adults. inactivated CoronaVac vaccine was most widely distributed worldwide essential early control SARS-CoV-2–related...
SARS-CoV-2 variants shaped the second year of COVID-19 pandemic and discourse around effective control measures. Evaluating threat posed by a new variant is essential for adapting response efforts when community transmission detected. In this study, we compare dynamics two variants, Alpha Iota, integrating genomic surveillance data to estimate reproduction number (R