A5058566484- PI3K/AKT/mTOR signaling in cancer
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Cancer-related molecular mechanisms research
- Advanced Biosensing Techniques and Applications
- Cancer Genomics and Diagnostics
- NF-κB Signaling Pathways
- RNA regulation and disease
- Immune cells in cancer
- Cancer Treatment and Pharmacology
- Neurogenesis and neuroplasticity mechanisms
- Lung Cancer Treatments and Mutations
- Cell Image Analysis Techniques
- Synthesis and biological activity
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- 3D Printing in Biomedical Research
- Cancer-related gene regulation
- Glycosylation and Glycoproteins Research
- Glioma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Molecular Biology Techniques and Applications
- FOXO transcription factor regulation
The University of Texas MD Anderson Cancer Center
2018-2024
UNC Lineberger Comprehensive Cancer Center
2009-2016
University of North Carolina at Chapel Hill
2009-2016
The Ohio State University
2011
University of California, Los Angeles
2011
VA Greater Los Angeles Healthcare System
2011
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2011
Ludwig Cancer Research
2011
Harvard University
2011
Indiana University School of Medicine
2011
Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role this protein kinase in cancer not well understood. Through an integrated analysis cell lines, vivo models, and clinical samples, we demonstrate mTORC2 frequently activated glioblastoma (GBM), most common malignant primary brain tumor adults. We show activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates activity, which partially suppressed by PTEN. signaling promotes GBM survival...
Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized therapy. Here we provide evidence TD-derived induced neural stem (iNSCs) an efficacious therapeutic strategy brain cancer. We find iNSCs genetically engineered with optical reporters and tumouricidal gene products retain capacity differentiate apoptosis co-cultured human glioblastoma cells....
Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. stem cells (GSCs) drive tumor formation, invasion, drug resistance and, as such, are the focus of studies identify new therapies for disease control. Here, we involvement IKK NF-κB signaling in maintenance GSCs. Inhibition this pathway impairs self-renewal analyzed tumorsphere formation GBM expansion brain slice culture. Interestingly, both canonical non-canonical branches shown contribute...
Abstract Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing biomarker identification. We established orthotopic PDX triple negative (TNBC) from the primary tumors patients prior to following neoadjuvant chemotherapy (NACT) while they were enrolled in ARTEMIS trial (NCT02276443). Serial biopsies obtained treatment (pre-NACT), poorly responsive disease after four cycles Adriamycin cyclophosphamide (AC,...
Abstract Triple negative breast cancer (TNBC) accounts for 15–20% of cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is current standard care patients early-stage TNBC. However, up to 70% TNBC have significant residual disease once NACT completed, which associated a high risk developing recurrence within two three years surgical resection. To identify targetable vulnerabilities chemoresistant TNBC, we generated longitudinal patient-derived...
Abstract There is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied a mouse model cancer reveals that the tumor niche characterized by expanded basal-like population, specialization subpopulations, mixed-lineage cells potentially serving transition state between luminal basal phenotypes. Despite vast cell-intrinsic differences, are functionally indistinguishable once...
A subset of breast cancer cell lines express a hypermethylation defect characterized by DNMT hyperactivity, overexpression DNMT3b, and silencing numerous genes. To investigate the role DNMT3b in defect, we examined effect RNAi‐mediated knockdown on expression methylation‐sensitive genes model hypermethylator lines: MDA‐MB‐453 BT549. Western blot analysis confirmed reduction cells transfected with RNAi targeting construct. RT‐PCR was used to analyze six (CEACAM6, CST6, ESR1, SCNN1A, GNA11,...
Abstract Chemotherapy, along with the PD1 inhibitor pembrolizumab, is recommended standard of care for patients primary triple negative breast cancer (TNBC). Nearly half TNBC treated neoadjuvant chemotherapy (NACT) have excellent responses. However, those significant residual burden (RCB) after NACT are at high risk recurrence or metastatic relapse within two years. Due to challenges posed by inter- and intratumoral heterogeneity TNBC, it critical develop appropriate models predicting...
SUMMARY Triple negative breast cancer (TNBC) that fails to respond neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies eradicate chemoresistant disease requires experimental models recapitulate the heterogeneity characteristic of TNBC. To end, we established a biobank 92 orthotopic patient-derived xenograft (PDX) TNBC from tumors 75 patients enrolled in ARTEMIS clinical trial ( NCT02276443 ) at MD Anderson Cancer Center, including 12 longitudinal sets generated...
Tumors are highly heterogeneous populations of cells, and measures intratumoral heterogeneity (ITH) diversity correlate with worse prognosis in many cancers, including breast cancer. Emerging studies highlighting functional interactions between subclones, as well among subclones components the tumor microenvironment. However, these have largely focused on soluble factors without interrogating spatial distribution defined by activated signaling pathways. Previous work this area has been...
Abstract Tumors are increasingly appreciated as complex ecosystems, wherein functional interactions between tumor subclones, well components of the microenvironment, contribute to progression and drug resistance. While some studies have focused on soluble factors that mediate these interactions, little is known about communication physically neighboring subclones (and their microenvironment). To investigate nature impact such localized we assessing activation status key cancer signaling...
Abstract Glioma, the most frequently occurring primary brain tumor, has a median survival of less than 15 months, despite multimodal treatment combining surgery, radiation, and chemotherapy. It been suggested that presence cancer stem cells (CSCs) within these tumors are responsible for resistance to high probability recurrence. As result, there is increasing interest in specifically targeting CSCs with new therapies improve this disease. NF-κB implicated numerous forms cancer, as its target...
Abstract Glioma, the most frequently occurring primary brain tumor, has a median survival of less than 15 months, despite multimodal treatment combining surgery, radiation, and chemotherapy. It been suggested that presence cancer stem cells (CSCs) within these tumors are responsible for resistance to high probability recurrence. As result, there is increasing interest in specifically targeting CSCs with new therapies improve this disease. NF-κB implicated numerous forms cancer, as its target...
<p>PDF file - 1MB</p>
<p>mp3 file (9.8 MB). In the November edition of Cancer Discovery podcast, Executive Editor Mark Landis talks with Paul S. Mischel about his paper, which identifies mTORC2 as a novel mediator drug resistance and regulator NF-κB signaling in glioblastoma.</p>
<p>PDF file - 161K</p>
<p>PDF file - 161K</p>
<p>PDF file - 1MB</p>
<p>mp3 file (9.8 MB). In the November edition of Cancer Discovery podcast, Executive Editor Mark Landis talks with Paul S. Mischel about his paper, which identifies mTORC2 as a novel mediator drug resistance and regulator NF-κB signaling in glioblastoma.</p>