A5064595278- Neurofibromatosis and Schwannoma Cases
- Neuroblastoma Research and Treatments
- Sarcoma Diagnosis and Treatment
- Soft tissue tumor case studies
- Meningioma and schwannoma management
- Protein Degradation and Inhibitors
- Glioma Diagnosis and Treatment
- Bone Tumor Diagnosis and Treatments
- Multiple Myeloma Research and Treatments
- Hair Growth and Disorders
- Hippo pathway signaling and YAP/TAZ
- Educational Technology and Pedagogy
- Soft tissue tumors and treatment
- Histiocytic Disorders and Treatments
- Nerve injury and regeneration
- Autoimmune Bullous Skin Diseases
- Neurogenesis and neuroplasticity mechanisms
- Cancer and Skin Lesions
- RNA regulation and disease
- Educational Technology and Assessment
- Eosinophilic Disorders and Syndromes
- Chronic Lymphocytic Leukemia Research
- melanin and skin pigmentation
- Sphingolipid Metabolism and Signaling
- Axon Guidance and Neuronal Signaling
The University of Texas Southwestern Medical Center
2014-2024
Southwestern Medical Center
2014-2024
University of Virginia
2024
Assistance Publique – Hôpitaux de Paris
2024
Texas Neurofibromatosis Foundation
2018-2023
Harold C. Simmons Comprehensive Cancer Center
2017-2023
Center for Neuroscience and Regenerative Medicine
2017-2023
NYU Langone Health
2022
Cells Therapy (Poland)
2021
Council of Science Editors
2021
PurposeBy incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) establish Legius syndrome (LGSS).MethodsWe used a multistep process, beginning with Delphi method involving global experts subsequently non-NF experts, patients, foundations/patient advocacy groups.ResultsWe reached consensus on minimal clinical genetic diagnosing differentiating NF1 LGSS, which have phenotypic overlap...
Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, neuroimaging.We used a multistep process, beginning Delphi method involving global disease experts subsequently non-neurofibromatosis clinical experts, patients, foundations/patient advocacy groups.We reached consensus on...
Although the biological actions of cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor. We show that is high-affinity ligand for G2A, lymphocyte-expressed G protein–coupled receptor whose genetic ablation results development autoimmunity. Activation G2A by increased intracellular calcium concentration, induced internalization, activated ERK mitogen-activated...
Abstract The ability to continuously deliver osteoinductive proteins a specific anatomic site would facilitate the treatment of fracture nonunions and other clinical problems associated with bone loss. We have developed murine model regional gene therapy. A bone‐marrow stromal cell line infected an adenovirus expressing recombinant morphogenetic protein‐2 cDNA secreted biologically active protein‐2. These protein‐2‐producing cells were able induce abundant heterotopic formation when...
Melanin protects the skin and eyes from harmful effects of UV irradiation, neural cells toxic insults, is required for sound conduction in inner ear. Aberrant regulation melanogenesis underlies disorders (melasma vitiligo), neurologic (Parkinson's disease), auditory (Waardenburg's syndrome), opthalmologic (age related macular degeneration). Much core synthetic machinery driving melanin production has been identified; however, spectrum gene products participating different physiological...
Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is most prevalent. A hallmark feature of mast infiltration, which recruited by chemoattractant stem factor (SCF) has been suggested to sustain tumorigenesis. In present study, we use new, genetically engineered Scf mice decipher contributions tumor-derived SCF cells development. We demonstrate that infiltration dependent on from cells. However, removal depleting main source only slightly...
Abstract Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop We show that neurons from mice tumor-causing Nf1 gene mutations exhibit hyperexcitability increased secretion activity-dependent tumor-promoting paracrine factors. discovered neurofibroma mitogen (COL1A2) produced by an activity-regulated...
Hypoxia-inducible factor (HIF)-1α is the oxygen-sensitive subunit of HIF-1, a transcriptional master regulator oxygen homeostasis. Oxygen-dependent prolyl hydroxylation targets HIF-1α for ubiquitinylation and proteasomal degradation. Unexpectedly, we found that exposing mice to elevated temperatures resulted in strong induction kidney, liver, spleen. To elucidate molecular mechanisms responsible this effect, HepG2 hepatoma cells were exposed different (34–42 °C) under normoxic (20%...
Cell cycle progression is monitored by highly coordinated checkpoint machinery, which activated to induce cell arrest until defects like DNA damage are corrected. We have isolated an anti-proliferative regulator named G2A (for G 2 accumulation), predominantly expressed in immature T and B lymphocyte progenitors a member of the seven membrane-spanning protein-coupled receptor family. overexpression attenuates transformation potential BCR-ABL other oncogenes, leads accumulation cells at /M...
Hypoxia-inducible factor (HIF) α subunits are induced under hypoxic conditions, when limited oxygen supply prevents prolyl hydroxylation-dependent binding of the ubiquitin ligase pVHL and subsequent proteasomal degradation. A short normoxic half-life HIF-α a very rapid protein stabilization crucial to cellular adaptation changing supply. However, molecular requirements for unusually mechanisms synthesis, folding nuclear translocation not well understood. We others previously found that...
Stem cells are under strict regulation by both intrinsic factors and the microenvironment. There is increasing evidence that many cancers initiate through acquisition of genetic mutations (loss control) in stem or their progenitors, followed alterations surrounding microenvironment extrinsic control). In neurofibromatosis type 1 (NF1), deregulation Ras signaling results development multiple neurofibromas, complex tumors peripheral nerves. Neurofibromas arise from Schwann cell lineage...
Abstract Neurofibromatosis type 1 (NF1) is a cancer predisposition disorder that results from inactivation of the tumor suppressor neurofibromin, negative regulator RAS signaling. Patients with NF1 present wide range clinical manifestations, and highest prevalence cutaneous neurofibroma (cNF). Most patients harboring cNF suffer greatly burden those tumors, which have no effective medical treatment. Ironically, none numerous mouse models developed so far recapitulate cNF. Here, we discovered...
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that develop sporadically or in neurofibromatosis type 1 (NF1) patients. There is no effective treatment for MPNSTs and they typically fatal. To gain insights into MPNST pathogenesis, we utilized an mouse model allowed us to study the evolution of these at transcriptome level. Strikingly, found upregulation a chromatin regulator, Brd4, show BRD4 inhibition profoundly suppresses both growth tumorigenesis. Our...
Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome caused by NF1 gene mutation, in which affected patients develop Schwann cell lineage peripheral nerve sheath tumors (neurofibromas). To investigate human neurofibroma pathogenesis, we differentiated series of isogenic, patient-specific NF1-mutant induced pluripotent stem cells (hiPSCs) into Schwannian (SLCs). We found that, although WT and heterozygous hiPSCs-SLCs did not form following mouse sciatic implantation,...
Abstract Neurofibromatosis Type I (NF1) is a neurocutaneous genetic syndrome characterized by wide spectrum of clinical presentations, including benign peripheral nerve sheath tumor called neurofibroma. These tumors originate from the Schwann cell lineage but other types as well extracellular matrix (ECM) in neurofibroma microenvironment constitute majority mass. In fact, collagen accounts for up to 50% neurofibroma’s dry weight. Although presence collagens indisputable, exact repertoire ECM...
Hair differentiates from follicle stem cells through progenitor in the matrix. In contrast to bulge, identities of progenitors and mechanisms by which they regulate hair shaft components are poorly understood. is also pigmented melanocytes follicle. However, niche that regulates follicular not well characterized. Here, we report identification matrix differentiated epithelial expressing transcription factor KROX20. Depletion Krox20 lineage results arrest growth, confirming critical role...
Neurofibromatosis type 1 (NF1) is an autosomal genetic disorder. Patients with NF1 are associated mono-allelic loss of the tumor suppressor gene in their germline, which predisposes them to develop a wide array benign lesions. Intriguingly, recent sequencing efforts revealed that frequently mutated multiple malignant tumors not typically patients, suggesting heterozygosity refractory at least some cancer types. In two orthogonal mouse models representing NF1- and non-NF1-related tumors, we...
Neurofibromatosis type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature neurofibromas an abundant collagen-rich extracellular matrix (ECM) that constitutes more than 50% tumor dry weight. However, little known about mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation enrichment plexiform (pNF) identified basement membrane...