A5016251331- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cancer Mechanisms and Therapy
- CRISPR and Genetic Engineering
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Multiple Myeloma Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Nanoparticle-Based Drug Delivery
- Biosimilars and Bioanalytical Methods
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Nanoplatforms for cancer theranostics
- Transgenic Plants and Applications
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Phagocytosis and Immune Regulation
- Mechanisms of cancer metastasis
- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- Heat shock proteins research
- Chemical Reactions and Isotopes
UCSF Helen Diller Family Comprehensive Cancer Center
2015-2024
University of California, San Francisco
2015-2024
Comprehensive Blood & Cancer Center
2023
University of San Francisco
2021
U-M Rogel Cancer Center
2019
Buck Institute for Research on Aging
2017
Sidney Kimmel Comprehensive Cancer Center
2017
City College of San Francisco
2012-2016
Hematology Oncology Associates
2013
Lawrence Berkeley National Laboratory
2008-2013
Phosphorylation of the α-subunit initiation factor 2 (eIF2) controls protein synthesis by a conserved mechanism. In metazoa, distinct stress conditions activate different eIF2α kinases (PERK, PKR, GCN2, and HRI) that converge on phosphorylating unique serine in eIF2α. This collection signaling pathways is termed 'integrated response' (ISR). phosphorylation diminishes synthesis, while allowing preferential translation some mRNAs. Starting with cell-based screen for inhibitors PERK signaling,...
KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDA) but remains an intractable pharmacologic target. Consequently, defining RAS effector pathway(s) required for PDA initiation and maintenance critical to improve treatment this disease. Here, we show that expression BRAF(V600E), not PIK3CA(H1047R), in the mouse pancreas leads intraepithelial neoplasia (PanIN) lesions. Moreover, concomitant BRAF(V600E) TP53(R270H) result lethal PDA. We tested inhibitors effectors against...
Abstract Purpose: To determine whether inhibition of TGFβ signaling prior to irradiation sensitizes human and murine cancer cells in vitro vivo. Experimental Design: TGFβ-mediated growth Smad phosphorylation MCF7, Hs578T, MDA-MB-231, T47D breast cell lines were examined correlated with clonogenic survival following graded radiation doses without pretreatment LY364947, a small molecule inhibitor the type I receptor kinase. The DNA damage response was assessed irradiated MDA-MB-231 pretreated...
<h3>Background</h3> Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools circumvent resistance. In human patients, responses checkpoint therapy correlate with tumor mutation load, intrinsic resistance associates pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis TGFβ signaling. <h3>Methods</h3> To facilitate studies on...
Inhibitors targeting KRASG12C, a mutant form of the guanosine triphosphatase (GTPase) KRAS, are promising new class oncogene-specific therapeutics for treatment tumors driven by protein. These inhibitors react with cysteine residue binding covalently to switch-II pocket (S-IIP) that is present only in inactive diphosphate (GDP)-bound sparing wild-type We used genome-scale CRISPR interference (CRISPRi) functional genomics platform systematically identify genetic interactions KRASG12C...
Immunotargeting of tumor-specific antigens is a powerful therapeutic strategy. Immunotherapies directed at MHC-I complexes have expanded the scope and enabled direct targeting intracellular oncoproteins cell surface. We asked whether covalent drugs that alkylate mutated residues on could act as haptens to generate unique MHC-I-restricted neoantigens. Here, we report KRAS G12C mutant cells treated with inhibitor ARS1620 present ARS1620-modified peptides in complexes. Using ARS1620-specific...
Targeted drug delivery systems that combine imaging and therapeutic modalities in a single macromolecular construct may offer advantages the development application of nanomedicines. To incorporate unique optical properties luminescent quantum dots (QDs) into immunoliposomes for cancer diagnosis treatment, we describe synthesis, biophysical characterization, tumor cell-selective internalization, anticancer QD-conjugated immunoliposome-based nanoparticles (QD-ILs). Pharmacokinetic vivo...
Multimodality imaging based on complementary detection principles has broad clinical applications and promises to improve the accuracy of medical diagnosis. This means that a tracer particle advantageously incorporates multiple functionalities into single delivery vehicle. In present work, we explore unique combination MRI photoacoustic tomography (PAT) detect picomolar concentrations nanoparticles. The nanoconstruct consists ferromagnetic (Co) particles coated with gold (Au) for...
The ability of certain breast cancers to resist a tyrosine kinase inhibitor drug may be overcome with high intermittent doses.
The PERK-eIF2α pathway is activated in aggressive prostate cancer and associated with patient outcome, providing a therapeutic target for the disease.
Hsp70 is a stress-inducible molecular chaperone that required for cancer development at several steps. Targeting the active site of has proven relatively challenging, driving interest in alternative approaches. collaborates with Bcl2-associated athanogene 3 (Bag3) to promote cell survival through multiple pathways, including FoxM1. Therefore, inhibitors Hsp70-Bag3 protein-protein interaction (PPI) may provide noncanonical way target this chaperone. We report JG-98, an allosteric inhibitor...
Cancer cells rely on the chaperone heat shock protein 70 (Hsp70) for survival and proliferation. Recently, benzothiazole rhodacyanines have been shown to bind an allosteric site Hsp70, interrupting its binding nucleotide-exchange factors (NEFs) promoting cell death in breast cancer lines. However, proof-of-concept molecules, such as JG-98, relatively modest potency (EC50 ≈ 0.7-0.4 μM) are rapidly metabolized animals. Here, we explored this chemical series through structure- property-based...
Multiple myeloma is incurable by standard approaches because of inevitable relapse and development treatment resistance in all patients. In our prior work, we identified a panel macropinocytosing human monoclonal antibodies against CD46, negative regulator the innate immune system, constructed antibody-drug conjugates (ADCs). this report, show that an anti-CD46 ADC (CD46-ADC) potently inhibited proliferation cell lines with little effect on normal cells. CD46-ADC also eliminated growth...
Abstract BRAF V600E mutation confers a poor prognosis in metastatic colorectal cancer (CRC) despite combinatorial targeted therapies based on the latest understanding of signaling circuitry. To identify parallel resistance mechanisms induced by BRAF–MEK–EGFR co-targeting, we used high-throughput kinase activity mapping platform. Here show that SRC kinases are systematically activated CRC following inhibition ± EGFR and coordinated targeting with increases treatment efficacy vitro vivo....
The human neurodegenerative and cancer predisposition condition ataxia-telangiectasia is characterized at the cellular level by radiosensitivity, chromosomal instability, impaired induction of ionizing radiation-induced cell cycle checkpoint controls. Recent work has revealed that gene defective in ataxia-telangiectasia, termed ATM , encodes an ≈350-kDa polypeptide, ATM, a member phosphatidylinositol 3-kinase family. We show binds DNA exploit this to purify near homogeneity. Atomic force...
We have isolated and sequenced genes from Saccharomyces cerevisiae (SRP54SC) Schizosaccharomyces pombe (SRP54sp) encoding proteins homologous to both the 54-kD protein subunit (SRP54mam) of mammalian signal recognition particle (SRP) product a gene unknown function in Escherichia coli, ffh (Römisch, K., J. Webb, Herz, S. Prehn, R. Frank, M. Vingron, B. Dobberstein. 1989. Nature (Lond.). 340:478-482; Bernstein H. D., A. Poritz, K. Strub, P. Hoben, Brenner, Walter. 340:482-486). To accomplish...
Androgen receptor (AR) inhibitors are used to treat multiple human diseases, including hirsutism, benign prostatic hypertrophy, and prostate cancer, but all available anti-androgens target only ligand binding, either by reduction of hormone or competitive antagonism. New strategies needed, could have an important impact on therapy. One approach be other cellular mechanisms required for activation. In prior work, we a cell-based assay AR conformation change identify non-ligand activity. Here,...