A5076625456- Chromatin Remodeling and Cancer
- Herpesvirus Infections and Treatments
- Glioma Diagnosis and Treatment
- interferon and immune responses
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Cancer Mechanisms and Therapy
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Sarcoma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Ocular Surface and Contact Lens
- Research on Leishmaniasis Studies
- Peripheral Neuropathies and Disorders
- Multiple Myeloma Research and Treatments
- Multiple Sclerosis Research Studies
- Immune Response and Inflammation
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- Toxin Mechanisms and Immunotoxins
- Bacterial Infections and Vaccines
- Cancer, Hypoxia, and Metabolism
- Hedgehog Signaling Pathway Studies
- Monoclonal and Polyclonal Antibodies Research
St. Jude Children's Research Hospital
2014-2024
Thermo Fisher Scientific (Sweden)
2024
Children's Research Hospital
2024
Cleveland Clinic
2024
Cedars-Sinai Medical Center
2010-2023
University of Colorado Denver
2020
Mexican Social Security Institute
2018
Sidney Kimmel Comprehensive Cancer Center
2017
Johns Hopkins Hospital
2017
Bloomberg (United States)
2017
Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB).
Herpes simplex virus (HSV) infection is a classic example of latent viral in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays major role the latency reactivation cycle thus recurrent disease. Whether presence LAT leads to generation dysfunctional T cell responses trigeminal ganglia (TG) latently infected mice not known. To address this issue, we used LAT-positive [LAT(+)] LAT-deficient [LAT(-)] viruses evaluate effect on CD8 exhaustion TG mice....
Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation RB1 gene. Children germline mutations in have high likelihood retinoblastoma and other malignancies later life. Genetically engineered mouse models share some similarities human but there are differences their cellular differentiation. To develop laboratory model formation, we make induced pluripotent stem cells (iPSCs) from 15 participants mutations. Each cell lines validated,...
// Melanie F. Weingart 1 , Jacquelyn J. Roth 7 Marianne Hutt-Cabezas Tracy M. Busse 8 Harpreet Kaur Antoinette Price Rachael Maynard Jeffrey Rubens Isabella Taylor Xing-gang Mao Jingying Xu 4 Yasumichi Kuwahara 3 Sariah Allen 6 Anat Erdreich-Epstein 4,5 Bernard E. Weissman Brent A. Orr Charles G. Eberhart Jaclyn Biegel 7,8,9 and Eric H. Raabe 1,2 Division of Neuropathology Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA 2 Pediatric Oncology, Lineberger...
Primitive myxoid mesenchymal tumor of infancy is a rare sarcoma that preferentially affects infants. It can be locally aggressive and rarely metastasizes, but the long-term outcome children with this mostly unknown. Histologically, it characterized by primitive cells abundant stroma. Internal tandem duplication B-cell CLL/lymphoma 6 (BCL6)-interacting co-repressor (BCOR) exon 15 has recently been described in clear cell kidney, central nervous system high-grade neuroepithelial BCOR...
Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as entity controversial. We analyzed cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH site-directed sequencing. Most cases demonstrated mutually exclusive MN1 rearrangements (n = 10) or BRAFV600E mutations 7). Two additional harbored RELA rearrangements. Other lacked these...
Abstract Anaplasia may be identified in a subset of tumors with presumed pilocytic astrocytoma ( PA ) component or piloid features, which associated aggressive behavior, but the biologic basis this change remains unclear. Fifty‐seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3–75) were included. A clinical diagnosis NF 1 was present 8 (22%). Alternative lengthening telomeres ALT assessed by telomere‐specific FISH and/or CISH . combination immunohistochemistry, DNA...
A hallmark of infection with herpes simplex virus type 1 (HSV-1) is the establishment latency in ganglia infected individual. During life latently individual, can occasionally reactivate, travel back to eye, and cause recurrent disease. Indeed, a major corneal scarring (CS) induced by HSV-1 following reactivation from latency. In this study, we evaluated relationship between amount CS level latency-associated transcript (LAT) trigeminal (TG) mice. Our results suggested that was not related...
Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and sequencing on 32 RIG tumors in vitro drug screen two cell lines. report that based methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, Ch. 13q 14q loss; focal PDGFRA CDK4 gain CDKN2A BCOR loss. Transcriptomically,...
The C-terminal (3') amino acid repeat region of the Plasmodium falciparum Ag Pf155/RESA, a vaccine candidate, contains immunodominant T and B cell epitopes. In order to identify additional epitopes in molecule, synthetic peptides corresponding centrally (5') located region, as well four nonrepeated regions, were synthesized. cells from 46 P. falciparum-primed individuals living holoendemic area Gambia where malaria transmission is seasonal tested for their responsiveness by thymidine...
Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune responses and can also increase survival. Interestingly, latency-associated transcript (LAT), the only viral gene consistently expressed during neuronal latency, enhances latency reactivation by promoting survival helping evade host response. However, mechanisms these LAT activities are not well understood. We show here first time that...
Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and ELISA in sera obtained from Gambian children before vaccination 3 weeks, 2 years, 5 years after with a + C capsular vaccine. Children 1-4 old at the time of vaccination. Most showed good initial response vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, both HA had returned prevaccination levels. This decline was not influenced...
Glycoprotein K (gK) is a virion envelope protein of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), which plays important roles in entry, morphogenesis egress. Two-hybrid pull-down assays were utilized to demonstrate that gK no other HSV-1 genes specifically binds signal peptide peptidase (SPP), also known as minor histocompatibility antigen H13. SPP dominant negative mutants, shRNA against significantly reduced replication vitro. affected lysosomes ER responses infection. Thus, this...
Abstract Bithalamic gliomas are rare cancers diagnosed based on poorly defined radiologic criteria. Infiltrative astrocytomas account for most cases. While some previous studies reported dismal outcomes patients with bithalamic irrespective of therapy and histologic grade, others described better prognoses even without anticancer therapy. Little is known about their molecular characteristics. We reviewed clinical, radiologic, features treated at our institution over 15 years. Targeted...
Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive infantile brain with poor survival. Recent advancements have highlighted significant molecular heterogeneity in AT/RT an subgroup featuring overexpression of the MYC proto-oncogene. We perform first comprehensive metabolic profiling patient-derived cell lines to identify therapeutic susceptibilities high MYC-expressing AT/RT.Metabolites were extracted from and separated ultra-high performance liquid chromatography mass spectrometry....
The HSV-1 latency reactivation cycle is the cause of significant human pathology. latency-associated transcript (LAT) functions by regulating and reactivation, in part inhibiting apoptosis. However, mechanism this process unknown. Here we show that LAT likely controls apoptosis via downregulation several components JAK-STAT pathway. Furthermore, provide evidence immune exhaustion not caused antiapoptotic activity LAT.
It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little known about innate immunity establishment viral latency. In current study, we investigated whether CD8α DCs impact by examining (TG) wild-type (WT) C57BL/6 versus CD8α−/− (lack functional and CD8α+ DCs), CD8β−/− (have β2m−/− but have DCs) mice as well BXH2 lack WT C3H We also determined phenotype could be restored adoptive transfer CD8+...
Abstract Atypical Teratoid Rhabdoid Tumor (AT/RT) is a rare pediatric central nervous system cancer often characterized by deletion or mutation of SMARCB1 , tumor suppressor gene. In this study, we found that regulates Human Endogenous Retrovirus K (HERV-K, subtype HML-2) expression. HML-2 repetitive element scattered throughout the human genome, encoding several intact viral proteins have been associated with stem cell maintenance and tumorigenesis. We env expression in both intracellular...
As part of the advancement in therapeutic decision-making for brain tumor patients at St. Jude Children's Research Hospital (SJCRH), we developed three robust classifiers, a deep learning neural network (NN), k-nearest neighbor (kNN), and random forest (RF), trained on reference series DNA-methylation profiles to classify central nervous system (CNS) types. The models' performance was rigorously validated against 2054 samples from two independent cohorts. In addition classic metrics model...
CD80 plays a critical role in stimulation of T cells and subsequent control infection. To investigate the effect on HSV-1 infection, we constructed recombinant virus that expresses two copies gene place latency associated transcript (LAT). This mutant (HSV-CD80) expressed high levels had similar replication kinetics as viruses rabbit skin cells. In contrast to parental virus, this expressing replicated efficiently immature dendritic (DCs). Additionally, susceptibility DCs HSV-CD80 infection...
Central nervous system (CNS)-type tumors and tumor-like proliferations arising in the gynecologic tract pelvis are rare. Clinicopathologic features of 23 cases reported using current WHO classification for CNS tumors, with selected relevant immunohistochemical molecular genetic analyses when possible. There were 12 embryonal including 7 medulloepitheliomas, 2 (not otherwise specified), 1 tumor multilayered rosettes, nodular desmoplastic medulloblastoma, medulloblastoma extensive nodularity,...