A5025725461- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- Advanced Proteomics Techniques and Applications
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Nuclear Structure and Function
- Mass Spectrometry Techniques and Applications
- Carcinogens and Genotoxicity Assessment
- Legionella and Acanthamoeba research
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Enzyme Structure and Function
- Cell death mechanisms and regulation
- Phytoplasmas and Hemiptera pathogens
- Bioinformatics and Genomic Networks
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Cancer therapeutics and mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Cornell University
2016-2025
Pediatrics and Genetics
2019-2025
Institut de Biologie Moléculaire et Cellulaire
2012-2023
Reproductive Science Center
2023
Universidad Fernando Pessoa Canarias
2023
Fundación Canaria de Investigación Sanitaria
2023
Hospital Universitario de Canarias
2023
Universidad de La Laguna
2023
University of California, San Diego
2005-2013
Ludwig Cancer Research
2005-2013
Protein phosphorylation is a post-translational modification widely used to regulate cellular responses. Recent studies showed that global analysis could be study signaling pathways and identify targets of protein kinases in cells. A key objective obtain an in-depth mapping low abundance cells; this necessitates the use suitable separation techniques because complexity phosphoproteome. Here we developed multidimensional chromatography technology, combining IMAC, hydrophilic interaction...
Understanding the role of DNA damage checkpoint kinases in cellular response to genotoxic stress requires knowledge their substrates. Here, we report use quantitative phosphoproteomics identify vivo kinase substrates yeast Mec1, Tel1, and Rad53 (orthologs human ATR, ATM, CHK2, respectively). By analyzing 2,689 phosphorylation sites wild-type various kinase-null cells, 62 from 55 proteins were found be controlled by checkpoint. Examination dependency each on Mec1 Tel1 or Rad53, combined with...
Hexanucleotide repeat expansion in the C9orf72 gene is a leading cause of frontotemporal lobar degeneration (FTLD) with amyotrophic lateral sclerosis (ALS). Reduced expression has been proposed as possible disease mechanism. However, cellular function remains to be characterized. Here we report identification two binding partners C9orf72: SMCR8 and WDR41. We show that WDR41 interacts C9orf72/SMCR8 heterodimer tightly associated Golgi complex. further demonstrate C9orf72/SMCR8/WDR41...
Torsional stress in chromatin plays a fundamental role cellular functions, influencing key processes such as transcription, replication, and organization. Transcription other may generate be regulated by torsional stress. In the genome, interplay of these creates complicated patterns both positive (+) negative (-) torsion. However, challenge generating an accurate torsion map is determining zero-torsion baseline signal, which conflated with accessibility. Here, we introduce high-resolution...
Mutations in the progranulin (PGRN) gene have been linked to two distinct neurodegenerative diseases, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests a critical role of PGRN lysosomes. However, how is trafficked lysosomes still not clear. Here we report novel pathway for lysosomal delivery PGRN. We found that prosaposin (PSAP) interacts with facilitates its targeting both biosynthetic endocytic pathways via cation-independent...
Significance Legionella pneumophila , the Legionnaires’ disease-causing bacterial pathogen, translocates a myriad of proteins, called effectors, into host cells. These proteins exploit normal cellular functions to facilitate intracellular growth. To identify these effectors has been major challenge. Here, we determined structure one such effector, substrate Icm/Dot transporter (SidC), which was previously thought be vesicle-tethering factor for recruiting endoplasmic reticulum (ER) vesicles...
Posttranslational protein modification by ubiquitin (Ub) is a central eukaryotic mechanism that regulates plethora of physiological processes. Recent studies unveiled an unconventional type ubiquitination mediated the SidE family Legionella pneumophila effectors, such as SdeA, catalyzes conjugation Ub to serine residue target proteins via phosphoribosyl linker (hence named PR-ubiquitination). Comparable deubiquitinases in canonical pathway, here we show 2 paralogous Lpg2154 (DupA;...
Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts muscle contractions, it was suggested that, when this production exceeds antioxidant capacity, preexisting pathways may be complemented by synthesis defense mechanism represented heat shock (HSPs), stress with function repair and maintaining protein folding. To test hypothesis, we analyzed carbonyl derivatives in plasma expression HSP72 activities enzymes from oxidative systems soleus...
In this paper, we describe how a dynamic regulatory process is necessary to restrict microvilli the apical aspect of polarized epithelial cells. We found that local phosphocycling regulation ezrin, critical plasma membrane–cytoskeletal linker microvilli, was required its function membrane. Proteomic approaches and ribonucleic acid interference knockdown identified lymphocyte-oriented kinase (LOK) SLK as relevant kinases. Using drug-resistant LOK variants showed these kinases were sufficient...
Pseudokinases are considered to be the inactive counterparts of conventional protein kinases and comprise approximately 10% human mouse kinomes. Here, we report crystal structure Legionella pneumophila effector protein, SidJ, in complex with eukaryotic Ca2+-binding regulator, calmodulin (CaM). The reveals that SidJ contains a kinase-like fold domain, which retains majority characteristic kinase catalytic motifs. However, fails demonstrate activity. Instead, mass spectrometry vitro...
Mutation in the GRN gene, encoding progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results frontotemporal lobar degeneration (FTLD) and complete loss neuronal ceroid lipofuscinosis (NCL). Although exact function of PGRN is unknown, it has been increasingly implicated lysosomal physiology. Here we report that interacts with enzyme, glucocerebrosidase (GCase), essential for proper GCase activity. activity significantly reduced tissue lysates...
Quantitative protein profiling is an essential part of proteomics and requires new technologies that accurately, reproducibly, comprehensively identify quantify the proteins contained in biological samples. We describe a strategy for quantitative based on separation labeled with isotope-coded affinity tag reagents by two-dimensional gel electrophoresis their identification quantification mass spectrometry. The method observation isotopically different precisely co-migrate during therefore...
Despite extensive studies, the molecular mechanism of DNA damage checkpoint activation remains incompletely understood. To better dissect this mechanism, we developed an activity-based assay for Dun1, a downstream check-point kinase in yeast, using its physiological substrate Sml1. Using assay, confirmed genetic basis Dun1 activation. Rad53 was found to be directly responsible We reconstituted by and that phosphorylation Thr-380 loop is Interestingly, evolutionarily conserved Thr-354 also...