A5019343919- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- DNA Repair Mechanisms
- Nuclear Structure and Function
- Lymphoma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Advanced Fluorescence Microscopy Techniques
- Cancer Mechanisms and Therapy
- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Cell death mechanisms and regulation
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Laser-Matter Interactions and Applications
- Cytokine Signaling Pathways and Interactions
- Spectroscopy Techniques in Biomedical and Chemical Research
- Retinoids in leukemia and cellular processes
- T-cell and Retrovirus Studies
- Photosynthetic Processes and Mechanisms
- Immune cells in cancer
- Acute Lymphoblastic Leukemia research
- Liver physiology and pathology
Stanford University
2015-2024
Stanford Medicine
2019
University of Konstanz
2012-2015
The Siglecs (sialic acid-binding immunoglobulin-like lectins) are glycoimmune checkpoint receptors that suppress immune cell activation upon engagement of cognate sialoglycan ligands. cellular drivers underlying Siglec ligand production on cancer cells poorly understood. We find the
Abstract The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). considered undruggable to date. Here, we comprehensively identify genes essential for survival of high but not low cells by a CRISPR/Cas9 genome-wide screen MYC-conditional HCC model. Our uncovers novel synthetic lethal (MYC-SL) interactions and identifies most MYC-SL described previously. In particular, the reveals nucleocytoplasmic transport be interaction. We show that majority are...
Protein function in eukaryotic cells is often controlled a cell cycle-dependent manner. Therefore, the correct assignment of cellular phenotypes to cycle phases crucial task biology research. Nuclear proteins whose localization varies during are valuable and frequently used markers progression. Proliferating nuclear antigen (PCNA) protein which involved DNA replication has dependent properties. In this work, we present tool identify particular, sub-stages phase (S-phase) based on...
The MYC oncogene drives T- and B- lymphoid malignancies, including Burkitt's lymphoma (BL) Acute Lymphoblastic Leukemia (ALL). Here, we demonstrate a systemic reduction in natural killer (NK) cell numbers SRα-tTA/Tet-O-MYCON mice bearing MYC-driven T-lymphomas. Residual mNK cells spleens of MYCON T-lymphoma-bearing exhibit perturbations the terminal NK effector differentiation pathway. Lymphoma-intrinsic arrests maturation by transcriptionally repressing STAT1/2 secretion Type I Interferons...
DEK is a biochemically distinct, conserved nonhistone protein that vital to global heterochromatin integrity. In addition, can be secreted and function as chemotactic, proinflammatory factor. Here we show exogenous penetrate cells, translocate the nucleus, there carry out its endogenous nuclear functions. Strikingly, adjacent cells take up from synovial macrophages. internalization heparan sulfate-dependent process, cellular uptake of into knockdown corrects depletion DNA repair deficits,...
Accurate assessment of changes in cellular differentiation status response to drug treatments or genetic perturbations is crucial for understanding tumorigenesis and developing novel therapeutics human cancer. We have developed a computational approach, the Lineage Maturation Index (LMI), define state hematopoietic malignancies based on their gene expression profiles. confirmed that LMI approach can detect known both normal malignant cells. To discover therapies, we applied this analyze...
Oncogene inactivation in both clinical targeted therapies and conditional transgenic mouse cancer models can induce significant tumor regression associated with the robust induction of apoptosis. Here we report that MYC-, RAS-, BCR-ABL-induced acute lymphoblastic leukemia (ALL), apoptosis upon oncogene is mediated by same pro-apoptotic protein, BIM. The BIMin MYC- RAS-driven downregulation miR-17-92. Overexpression miR-17-92 blocked MYC but not BCR-ABL-driven ALL leukemia. Hence, our results...
Abstract Understanding the cellular response to DNA strand breaks is crucial decipher mechanisms maintaining integrity of our genome. We present a novel method visualize how mobility nuclear proteins changes in localized damage. are induced via nonlinear excitation with femtosecond laser pulses at λ = 1050 nm 3D‐confined subnuclear volume. After time delay choice, protein within this volume analysed by two‐photon photoactivation PA‐GFP fusion 775 nm. By changing position spot respect zone...
Abstract MYC activation and dysregulation is a powerful oncogenic driver in multiple cancers, including diffuse large B cell lymphoma (DLBCL). There known correlation between expression poor prognosis. While the 5-year overall survival for DLBCL patients on first-line therapy, R-CHOP, approximately 75%, drops to staggering 30% co-expressing BCL2 (double expressor lymphoma). However, it challenging target directly. Therefore, we identified novel approach circumvent targeting directly by...
Abstract Hepatocellular carcinoma (HCC) is an aggressive tumor, and treatment options for patients with unresectable HCC are limited to targeted therapies immunotherapy. The activation dysregulation of MYC have been implicated in multiple cancers, including HCC, where approximately 30% human samples show gene amplification. However, it challenging target directly. Therefore, we applied a novel approach circumvent targeting directly by leveraging Pepper’s proprietary transomic analysis...
Abstract The MYC oncogene is frequently overexpressed in human cancers. However, targeting directly has proven to be extremely difficult and itself currently considered undruggable. We sought identify alternative genetic vulnerabilities of MYC-driven cancer by using CRISPR-based genome-wide synthetic lethality screens. library screens were performed a cell line derived from our transgenic mouse model hepatocellular carcinoma. In this line, the level regulated Tet-Off system. Using lentiviral...
Abstract The MYC oncogene drives T and B lymphoid malignancies, including Burkitt’s lymphoma (BL) Acute Lymphoblastic Leukemia (ALL). Using CyTOF, we demonstrate a systemic reduction in natural killer (NK) cell-mediated surveillance SRα-tTA/Tet-O-MYC ON mice bearing MYC-driven T-lymphomas, due to an arrest NK cell maturation. Inactivation of lymphoma-intrinsic releases the brakes on maturation restoring homeostasis. Lymphoma-intrinsic arrests by transcriptionally repressing STAT1/2 secretion...
Abstract Accurate assessment of changes in cellular differentiation status response to drug treatments or genetic perturbations is crucial for understanding tumorigenesis and developing novel therapeutics human cancer. We have developed a computational approach, the Lineage Maturation Index (LMI), define state hematopoietic malignancies based on their gene expression profiles. confirmed that LMI approach can detect known both normal malignant cells. To discover therapies, we applied this...
We employ near-infrared femtosecond pulses to probe local alterations of chromatin dynamics caused by DNA strand breaks. Nonlinear confocal nanomanipulation enables us visualize how damage signaling emanates spatio-temporally in a live cell.