A5052972832- Glioma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cerebrospinal fluid and hydrocephalus
- Vascular Malformations Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Nanoparticle-Based Drug Delivery
- Cancer Cells and Metastasis
- Neuroblastoma Research and Treatments
- Meningioma and schwannoma management
- Neurogenesis and neuroplasticity mechanisms
- Angiogenesis and VEGF in Cancer
- Advanced Neuroimaging Techniques and Applications
- Spinal Dysraphism and Malformations
- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Nanoplatforms for cancer theranostics
- Intracranial Aneurysms: Treatment and Complications
University of Utah
2018-2025
Primary Children's Hospital
2018-2025
Huntsman Cancer Institute
2019-2025
Vanderbilt University Medical Center
2023
Neurological Surgery
2020-2023
Intermountain Healthcare
2021-2022
Stanford University
2008-2019
Lucile Packard Children's Hospital
2014-2019
California Institute for Regenerative Medicine
2008-2019
Medical University of South Carolina
2019
A rare set of hematopoietic stem cells (HSC) must undergo a massive expansion to produce mature blood cells. The phenotypic isolation HSC from mice offers the opportunity determine directly their proliferation kinetics. We analyzed and cell cycle kinetics long-term self-renewing (LT-HSC) in normal adult mice. At any one time, approximately 5% LT-HSC were S/G2/M phases another 20% G1 phase. BrdUrd incorporation was used rate at which different cohorts entered over time. About 50% incorporated...
Anti-CD47 antibody is effective for treating malignant pediatric brain tumors without detectable toxicity in patient-derived xenograft models.
Abstract Purpose: MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate targeting for the treatment of medulloblastoma. Experimental Design: We evaluated effects genetic pharmacologic bromodomains on proliferation, cell cycle, apoptosis...
In this work we have uncovered a role for Wnt signaling as an important regulator of stem cell self-renewal in the developing brain. We identified Wnt-responsive cells subventricular zone E14.5 mouse Responding populations were enriched self-renewing primary culture, suggesting that is hallmark activity vivo. also tested whether signals directly influence neural cells. Using inhibitors pathway, found required efficient cloning and expansion single-cell derived are able to generate new well...
To derive quantitative image features from magnetic resonance (MR) images that characterize the radiographic phenotype of glioblastoma multiforme (GBM) lesions and to create radiogenomic maps associating these with various molecular data.
Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display continuum of different polarization states between antitumorigenic M1 protumorigenic M2 phenotypes, with lower M1/M2 ratio correlating worse prognosis. Here, we investigated effect macrophage on anti-CD47 antibody-mediated phagocytosis human cells in vitro, as well distribution versus grown mouse xenografts....
Significance Macrophage-mediated programmed cell removal (PrCR) plays an essential role in tumor surveillance and elimination. Blockade of the don't-eat-me signal CD47 on cells allows already expressed eat-me signals to induce PrCR eliminate cells. To date molecular mechanism by which macrophages recognize phagocytose remains unclear. This paper demonstrates that activation Toll-like receptor (TLR) pathways induces phosphorylation Bruton's tyrosine kinase (Btk), catalyzes cell-surface...
Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the microenvironment. Hence, modulation reeducation of tumor-associated GBM considered promising antitumor strategy. Resident invading shown distinct origin function. Whereas yolk sac-derived reside brain, blood-derived monocytes invade central nervous system only under pathological...
Hematopoietic stem cells (HSC) give rise to of all hematopoietic lineages, many which are short lived. HSC face developmental choices: self-renewal (remain an with long-term multilineage repopulating potential) or differentiation (become short-term potential and, eventually, a mature cell). There is large overcapacity differentiating and apoptosis plays role in regulating their numbers. It not clear whether direct To address this, we have employed transgenic mouse model that overexpresses...
Reactivation of telomerase and maintenance telomere length can lead to the prevention replicative senescence in some human somatic cells grown vitro. To investigate whether shortening might also play a role limitation hematopoietic stem cell (HSC) division capacity vivo, we analyzed during serial transplantation murine HSCs. Southern blot analysis donor bone marrow revealed extensive (∼7 kb) after just two rounds HSC transplantation. The number cycling HSCs increased remained elevated for at...
Distinct molecular subgroups of pediatric medulloblastoma confer important differences in prognosis and therapy. Currently, tissue sampling is the only method to obtain information for classification. Our goal was develop validate radiomic machine learning approaches predicting medulloblastoma.In this multi-institutional retrospective study, we evaluated MR imaging datasets 109 patients with from 3 children's hospitals January 2001 2014. A computational framework developed extract...
CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though mAbs have entered clinical trials, diagnostic tests for monitoring therapy response vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used "off label" as a contrast agent: the nanoparticle-based drug phagocytosed by TAM detected with magnetic resonance imaging (MRI). We evaluated if ferumoxytol-enhanced MRI monitor...
Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection patient groups suitable targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant molecular subgroups. Materials Methods In this retrospective study, consecutive patients with newly diagnosed at MRI 12 international sites between July 1997 May 2020...
Background While major advances have been made in improving the quality of life and survival children with most forms medulloblastoma (MB), those MYC-driven tumors (Grp3-MB) still suffer significant morbidity mortality. There is an urgent need to explore multimodal therapeutic regimens which are effective safe for children. Large-scale studies revealed abnormal cancer epigenomes caused by mutations structural alterations chromatin modifiers, aberrant DNA methylation, histone modification...
Abstract Approximately half of melanoma patients relapse or fail to respond current standards care, highlighting the need for new treatment options. Engineering T-cells with chimeric antigen receptors (CARs) has revolutionized hematological malignancies but been clinically less effective in solid tumors. We therefore sought engineer alternative immune cell types inhibit progression. macrophages CARs emerged as a promising approach overcome some challenges faced by CAR-T cells; however,...
Background and Purpose— Intravascular delivery of neural stem cells (NSCs) after stroke has been limited by the low efficiency transendothelial migration. Vascular cell adhesion molecule-1 is an endothelial molecule known to be upregulated early responsible for firm inflammatory expressing surface integrin, CD49d. We hypothesize that enriching NSCs express CD49d injecting them into carotid artery would improve targeted injured brain. Methods— Mouse were analyzed expression fluorescence...