A5009384413- Cellular Mechanics and Interactions
- Axon Guidance and Neuronal Signaling
- Angiogenesis and VEGF in Cancer
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Congenital heart defects research
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Immunotherapy and Immune Responses
- Skin and Cellular Biology Research
- Endoplasmic Reticulum Stress and Disease
- Estrogen and related hormone effects
- Muscle Physiology and Disorders
- Connective tissue disorders research
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Advanced Fluorescence Microscopy Techniques
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- Hippo pathway signaling and YAP/TAZ
- Cancer Immunotherapy and Biomarkers
- 3D Printing in Biomedical Research
Genentech
2010
Massachusetts Institute of Technology
2002-2004
Howard Hughes Medical Institute
1998-1999
Johns Hopkins University
1998
University of Chicago
1998
Universitat Autònoma de Barcelona
1998
Hospital Universitari Germans Trias i Pujol
1998
Northwestern University
1996
Mice lacking desmin produce muscle fibers with Z disks and normal sarcomeric organization. However, the muscles are mechanically fragile degenerate upon repeated contractions. We report here a human patient severe generalized myopathy aberrant intrasarcoplasmic accumulation of intermediate filaments. Muscle tissue from this lacks wild-type allele has gene mutation encoding 7-aa deletion within coiled-coil segment protein. show that recombinant harboring cannot form proper filament networks...
Mammalian Nck1 and Nck2 are closely related adaptor proteins that possess three SH3 domains, followed by an SH2 domain, implicated in coupling phosphotyrosine signals to polypeptides regulate the actin cytoskeleton. However, vivo functions of have not been defined. We mutated murine genes incorporated β-galactosidase reporters into mutant loci. In mouse embryos, two Nck broad overlapping expression patterns. They functionally redundant sense mice deficient for either or viable, whereas...
Dendritic cells (DCs) promote adaptive immunity by cross-presenting antigen-based epitopes to CD8+ T cells. DCs process internalized protein antigens into peptides that enter the endoplasmic reticulum (ER), bind major histocompatibility type I (MHC-I) complexes, and are transported cell surface for cross-presentation. can exhibit activation of ER stress sensor IRE1α without stress, but underlying mechanism remains obscure. Here, we show antigen-derived hydrophobic directly engage ER-resident...
The tumor suppressor Lkb1/STK11/Par-4 is a key regulator of cellular energy, proliferation, and polarity, yet its mechanisms action remain poorly defined. We generated mice harboring mutant Lkb1 knockin allele that allows for rapid inhibition kinase. Culturing embryonic tissues, we show acute loss kinase activity perturbs epithelial morphogenesis without affecting cell polarity. In pancreas, cystic structures developed rapidly after inhibition. lung, resulted in cell-autonomous branching...
We demonstrated previously that glucocorticoids differentially affect the levels of two pituitary gonadotropins, LH and FSH, both in vivo vitro. In vivo, effect is GnRH independent, indicating a direct action on gonadotrope, it leads to selective up-regulation content FSH beta-subunit messenger RNA (mRNA). The objective present study was confirm corticosterone (B) mRNA primary anterior cell culture assess whether B-induced rise beta mediated through altered stability transcript. Anterior...
Abstract Background: Phase 3 trials (IMpassion130, KEYNOTE-355) have shown improved efficacy with the addition of immune checkpoint modulators to chemotherapy in PD-L1 +ve aTNBC. However, unmet need remains ~60% pts aTNBC who -ve tumors. Preliminary data from a multicenter phase 1b study (NCT03800836) evaluating safety and oral AKT inhibitor IPAT + atezo paclitaxel/nab-paclitaxel showed promising antitumor activity (73% confirmed objective response rate) irrespective status [Schmid, AACR...
Abstract The tumor suppressor Lkb1 is a regulator of cellular energy, proliferation, and polarity, yet the mechanism by which it controls tissue morphogenesis or cancer remains poorly defined. By culturing embryonic tissues from mice harboring mutant that can be rapidly inhibited, we have previously shown acute loss results in destabilized architecture formation highly dynamic pancreatic cysts (Lo et al, JCB 2012). Remarkably, evolve within few days into precancerous-like lesions now...
<h3>Background</h3> The development of adoptive cell therapy has made the understanding T-cell target recognition and activation crucial to cancer treatment. Indeed, success many these therapies directly depends on our ability predict or measure specificity receptors (TCR) neoantigens understand how specificities translate into activation. While dynamics TCR-pMHC binding have been under careful scrutiny for a long time, fundamental unknowns remain regarding aspects that relate immune...
ABSTRACT Dendritic cells (DCs) promote adaptive immunity by cross-presenting antigen-based epitopes to CD8 + T cells. DCs process internalized protein antigens into peptides that enter the endoplasmic reticulum (ER) and upload onto major histocompatibility type I (MHC-I) complexes for cell-surface transport cross-presentation. Perplexingly, often exhibit activation of ER-stress sensor IRE1α in absence classical ER stress—leaving underlying mechanism unexplained. Here we show antigen-derived...