A5013514856- Glioma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- Cancer and Skin Lesions
- Protein Degradation and Inhibitors
- Nonmelanoma Skin Cancer Studies
- MicroRNA in disease regulation
- Chemokine receptors and signaling
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- interferon and immune responses
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Radiomics and Machine Learning in Medical Imaging
- SARS-CoV-2 and COVID-19 Research
- Cancer Immunotherapy and Biomarkers
- Multiple Myeloma Research and Treatments
- Ferroptosis and cancer prognosis
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Salivary Gland Tumors Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
Cornell University
2011-2023
Weill Cornell Medicine
2020-2023
UPMC Hillman Cancer Center
2008-2023
Memorial Sloan Kettering Cancer Center
2012-2022
UCLA Jonsson Comprehensive Cancer Center
2011
Institute for Molecular Medicine
2011
University of California, Los Angeles
2011
Baylor College of Medicine
2010
University of Minnesota
2010
Neurological Surgery
2009
Abstract Protein phosphorylation is one of the most widespread post-translational modifications in biology 1,2 . With advances mass-spectrometry-based phosphoproteomics, 90,000 sites serine and threonine have so far been identified, several thousand associated with human diseases biological processes 3,4 For vast majority events, it not yet known which more than 300 protein serine/threonine (Ser/Thr) kinases encoded genome are responsible 3 Here we used synthetic peptide libraries to profile...
// Kasthuri Kannan 1,4 , Akiko Inagaki 2 Joachim Silber Daniel Gorovets Jianan Zhang Edward R. Kastenhuber Adriana Heguy 4 John H. Petrini Timothy A. Chan 3,4 and Jason T. Huse 1 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Molecular Biology, 3 Radiation Oncology, Human Oncology Pathogenesis Program, Correspondence: Huse, email: Keywords : glioma, astrocytoma, IDH, ATRX, whole-exome sequencing Received October 01, 2012, Accepted 09, Published 11, 2012...
A hallmark of metastasis is the adaptation tumor cells to new environments. Metabolic constraints imposed by serine and glycine-limited brain environment restrict metastatic growth. How metastases overcome these growth-prohibitive conditions poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes rate-limiting step glucose-derived synthesis, a major determinant in multiple human cancer types preclinical models. Enhanced synthesis proved...
The RNase III endonuclease Dicer plays a key role in generation of microRNAs (miRs). We hypothesized that regulates cancer cell susceptibility to immune surveillance through miR processing. Indeed, disruption up-regulated intercellular adhesion molecule (ICAM)-1 and enhanced the tumor cells antigen-specific lysis by cytotoxic T-lymphocytes (CTLs), while expression other immunoregulatory proteins examined was not affected. Blockade ICAM-1 inhibited specific CTLs against Dicer-disrupted cells,...
Significance Efforts to understand and treat fibrolamellar hepatocellular carcinoma (FL-HCC) have been confounded by a lack of models that accurately reflect the genetics biology disease. Here we demonstrate Dnajb1–Prkaca gene fusion drives tumorigenesis in mice, DNAJB1 FL-HCC initiation more effectively than wild-type PRKACA overexpression. The requirement kinase domain tumor establishes potential utility inhibitors targeting fusion. By identifying genetic environmental factors can enhance...
Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in understanding glioblastoma [World Health Organization (WHO) IV], its malignant subtype, lower grade (WHO II and III) glioma variants remain comparatively understudied, especially light their notable clinical heterogeneity. Accordingly, we sought to identify characterize clinically relevant molecular subclasses diffuse astrocytic gliomas.We conducted multidimensional profiling,...
Abstract In contrast to normal cells, cancer cells avidly take up glucose and metabolize it lactate even when oxygen is abundant, a phenomenon referred as the Warburg effect. This fundamental alteration in metabolism enables their specific detection by positron emission tomography (PET) following i.v. injection of analogue 18F-fluorodeoxy-glucose (18FDG). However, this useful imaging technique limited fact that not all cancers FDG. To identify molecular determinants 18FDG retention, we...
Coagulopathy is a significant aspect of morbidity in COVID-19 patients. The clotting cascade propagated by series proteases, including factor Xa and thrombin. While certain host TMPRSS2 furin, are known to be important for cleavage activation SARS-CoV-2 spike promote viral entry the respiratory tract, other proteases may also contribute. Using biochemical cell-based assays, we demonstrate that thrombin can directly cleave spike, enhancing infection at stage entry. Coagulation factors...
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or experience breakthrough infections. Understanding common host factors necessary for life cycles of may reveal conserved therapeutic targets. Here, we used known substrate specificities mammalian protein kinases to deconvolute...
Abstract Menin interacts with oncogenic MLL1-fusion proteins, and small molecules that disrupt these associations are in clinical trials for leukemia treatment. By integrating chromatin-focused genome-wide CRISPR screens genetic, pharmacologic, biochemical approaches, we discovered a conserved molecular switch between the MLL1–Menin MLL3/4–UTX chromatin-modifying complexes dictates response to Menin–MLL inhibitors. safeguards survival by impeding binding of complex at subset target gene...
Abstract Purpose: A variety of cancers, including malignant gliomas, overexpress transforming growth factor-β (TGF-β), which helps tumors evade effective immune surveillance through a mechanisms, inhibition CD8+ CTLs and enhancing the generation regulatory T (Treg) cells. We hypothesized that TGF-β would improve efficacy vaccines targeting glioma-associated antigen (GAA)–derived CTL epitopes by reversal immunosuppression. Experimental Design: Mice bearing orthotopic GL261 gliomas were...
Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head neck squamous cell carcinoma. Targeted agents such as cetuximab erlotinib are currently used patients with carcinoma, but, this disease, genomic alterations that cause activation determine response pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection EGFR/PI3K pathway, composed sequencing core components,...
In an attempt to develop effective vaccines against central nervous system (CNS) tumors, we evaluated the ability of with standard dendritic cells (DC) versus type 1 polarizing DCs (DC1) induce glioma-specific CTLs CNS tumor-relevant homing properties and mechanism their action. C57BL/6 mouse-derived bone marrow were cultured mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) for 6 days, CD11c(+) subsequently GM-CSF, rmIFN-gamma, rmIFN-alpha, rmIL-4, polyinosinic-polycytidylic...
We hypothesized that the type 1 IFNs would play a pivotal role in antiglioma immunosurveillance through promotion of adaptive immunity and suppression immunoregulatory cells.
Abstract Mutations in the TP53 tumor suppressor gene are common many cancer types, including acute myeloid leukemia (AML) subtype known as complex karyotype AML (CK-AML). Here, we identify a gain-of-function (GOF) Trp53 mutation that accelerates CK-AML initiation beyond p53 loss and, surprisingly, is required for disease maintenance. The Trp53R172H (TP53R175H humans) exhibits neomorphic function by promoting aberrant self-renewal leukemic cells, phenotype present hematopoietic stem and...