A5057026801- CRISPR and Genetic Engineering
- Glutathione Transferases and Polymorphisms
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Genomics, phytochemicals, and oxidative stress
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- CAR-T cell therapy research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Inflammasome and immune disorders
- Ubiquitin and proteasome pathways
- interferon and immune responses
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
- Immune Response and Inflammation
- Viral Infectious Diseases and Gene Expression in Insects
Université de Montréal
2024
Northwestern University
2007-2022
Genentech
2012-2016
Washington Hospital
2013
Novartis (United States)
2013
Neurological Surgery
2013
Environmental Energy & Engineering
2012
Middlebury Institute of International Studies at Monterey
2012
Innovative Genomics Institute
2009-2011
University of California, Berkeley
2008-2011
To act as guides in the RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) must be unwound into their component strands, then assembled with proteins to form RNA-induced silencing complex (RISC), which catalyzes target messenger cleavage. Thermodynamic differences base-pairing stabilities of 5' ends two approximately 21-nucleotide siRNA strands determine strand is RISC. We show that Drosophila, orientation Dicer-2/R2D2 protein heterodimer on duplex determines associates core...
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication immune system. Therapeutic use blocking antibodies to PD-L1 or its PD-1 has produced unparalleled, durable clinical responses, with highest likelihood response seen in patients whose tumour cells express before therapy. The significance expression each cell type emerged as a central and controversial unknown development immunotherapeutics. Using...
Colon tumors arise in a stepwise fashion from either discrete genetic perturbations or epigenetic dysregulation. To uncover the key regulators that drive colon cancer growth, we used CRISPR loss-of-function screen and identified number of essential genes, including bromodomain extraterminal (BET) protein BRD4. We found BRD4 is critical for proliferation, its knockdown led to differentiation effects vivo. JQ1, BET inhibitor, preferentially reduced growth subset epigenetically dysregulated...
A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, the ability to evade immune system, is vital cancer propagation. An increased understanding how this achieved critical identifying or improving therapeutic interventions. In study, using acute myeloid leukemia (AML) human lines a custom CRISPR/Cas9 screening platform, we identify H3K9 methyltransferase SETDB1 as novel, negative regulator innate immunity....
Pyroptosis requires the induction of gasdermin D expression by transcription factor IRF2.
The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor GSDMD. is enteroinvasive bacterium causes hemorrhagic gastroenteritis in primates, but not rodents. contributes species specificity by ubiquitinating human, mouse, GSDMD and targeting it for...
Breast cancer has been redefined into three clinically relevant subclasses: (i) estrogen/progesterone receptor positive (ER+/PR+), (ii) HER2/ERRB2 positive, and (iii) those lacking expression of all markers (triple negative or basal-like). While targeted therapies for ER+/PR+ HER2+ tumors have revolutionized patient treatment increased lifespan, an urgent need exists identifying novel targets triple-negative breast cancers. Here, we used integrative genomic analysis to identify candidate...
The 3' termini of eukaryotic mRNAs influence transcript stability, translation efficiency, and subcellular localization. Here we report that a subset developmental regulatory genes, enriched in critical RNA-processing factors, exhibits synchronous lengthening their UTRs during embryogenesis. resulting are up to 20-fold longer than those found on typical Drosophila mRNAs. large emerge shortly after the onset zygotic transcription, with several these genes acquiring additional, phased UTR...
Antibody-drug conjugates (ADC) are designed to selectively bind tumor antigens via the antibody and release their cytotoxic payload upon internalization. Controllable through judicious design of linker has been an early technological milestone. Here, we examine effect protease-cleavable valine-citrulline [VC(S)] on ADC efficacy. The VC(S) was be cleaved by cathepsin B, a lysosomal cysteine protease. Surprisingly, suppression B expression CRISPR-Cas9 gene deletion or shRNA knockdown had no...
Abstract The NLRC4 inflammasome recognizes bacterial flagellin and components of the type III secretion apparatus. stimulation leads to caspase-1 activation followed by a rapid lytic cell death known as pyroptosis. is linked pathogen-free auto-inflammatory diseases, suggesting role for in sterile inflammation. Here, we show that activates an alternative program morphologically similar apoptosis caspase-1-deficient BMDMs. By performing unbiased genome-wide CRISPR/Cas9 screen with subsequent...
ER-targeted therapeutics provide valuable treatment options for patients with ER+ breast cancer, however, current relapse and mortality rates emphasize the need improved therapeutic strategies. The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance advanced on ERα signaling, provides strong rationale continued targeting ERα. Here we describe GDC-0810, novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was...
Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed a potential treatment for obesity-linked disorders. Here, we describe the generation humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, common FGF21 and FGF19. Using this molecule, show antibody-mediated activation FGFR1/βKlotho complex in mice induces sustained energy expenditure BAT, browning white tissue,...
Multiple myeloma (MM) arises from malignant immunoglobulin (Ig)-secreting plasma cells and remains an incurable, often lethal disease despite therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM may co-opt IRE1α-XBP1s pathway; however, validity of as potential target is controversial. Genetic disruption or XBP1s, pharmacologic kinase inhibition, attenuated...