A5064078708- PARP inhibition in cancer therapy
- Electrostatic Discharge in Electronics
- Toxin Mechanisms and Immunotoxins
- Integrated Circuits and Semiconductor Failure Analysis
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Plant nutrient uptake and metabolism
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- ATP Synthase and ATPases Research
- Fungal and yeast genetics research
- Amino Acid Enzymes and Metabolism
- Calcium signaling and nucleotide metabolism
- Molecular Biology Techniques and Applications
- Bioinformatics and Genomic Networks
- Viral Infections and Immunology Research
- DNA and Nucleic Acid Chemistry
- Drug Transport and Resistance Mechanisms
- Mechanisms of cancer metastasis
- Genomics and Chromatin Dynamics
- HIV/AIDS drug development and treatment
- Signaling Pathways in Disease
Santa Clara University
2020-2023
Oregon Health & Science University
2014-2018
Harvard University
2006-2012
Howard Hughes Medical Institute
2007-2012
Center for Systems Biology
2007-2012
Colorado College
2006-2008
Adenosine diphosphate ribosyltransferases (ARTDs; ARTD1-17 in humans) are emerging as critical regulators of cell function both normal physiology and disease. These enzymes transfer the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD(+)), to amino acids target proteins. The functional redundancy overlapping specificities among 17 ARTDs humans make identification direct targets individual ARTD family members a cellular context formidable challenge. Here we...
ADP-ribosyltransferases (ARTD1–16) have emerged as major downstream effectors of NAD+ signaling in the cell. Most ARTDs (ARTD7 and 8, 10–12, 14–17) catalyze transfer a single unit ADP-ribose from to target proteins, process known mono-ADP-ribosylation (MARylation). Progress understanding cellular functions MARylation has been limited by inability identify direct targets for individual mono-ARTDs. Here, we engineered mono-ARTDs use an analog that is orthogonal wild-type ARTDs. We profiled...
Abstract Background Inorganic phosphate is an essential nutrient required by organisms for growth. During starvation, Saccharomyces cerevisiae activates the signal transduction (PHO) pathway, leading to expression of secreted acid phosphatase, PHO5 . The fission yeast, Schizosaccharomyces pombe , regulates ScPHO5 homolog ( pho1 + ) via a non-orthologous PHO pathway involving genetically identified positive pho7 and negative csk1 regulators. genes induced limitation molecular mechanism which...
Poly(ADP-ribose) polymerase 14 (PARP14) is a member of the PARP family enzymes that transfer ADP-ribose from NAD+ to nucleophilic amino acids on target proteins, process known as mono-ADP-ribosylation (MARylation). PARP14 involved in normal immune function through IL-4 signaling pathway and prosurvival factor multiple myeloma hepatocellular carcinoma. A mechanistic understanding physiological pathophysiological roles has been limited by dearth PARP14-specific MARylation targets. Herein we...
Abstract Poly‐ADP‐ribose polymerases (PARPs) comprise a family of 17 distinct enzymes that catalyze the transfer ADP‐ribose from nicotinamide adenine dinucleotide (NAD + ) to acceptor sites on protein targets. PARPs have been implicated in number essential signaling pathways regulating both normal cell function and pathophysiology. To understand physiological role each PARP member we need identify direct targets for unique cellular context. PARP‐family member‐specific target identification...
Poly(ADP-ribose) polymerases, PARPs, transfer ADP-ribose onto target proteins from nicotinamide adenine dinucleotide (NAD+). Current mass spectrometric analytical methods require proteolysis of proteins, limiting the study dynamic ADP-ribosylation on contiguous proteins. Herein, we present a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method that facilitates multisite analysis ADP-ribosylation. We observe divergent dynamics for catalytic domains PARPs 14 and 15,...
RNA structures contain many bulges and loops that are expected to be sites for inter- intra-molecular interactions. Nucleotides in the bulge influence structure recognition of RNA. The same stability is assigned all trinucleotide bulged current secondary prediction models. In this study thermal denaturation experiments were performed on four RNA, context HIV-1 TAR determine whether sequence affects its divalent ion Cytosine-rich more stable than uracil-rich 1 M KCl. Interactions ions...
The transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) to target proteins is mediated by a class human diphtheria toxin-like ADP-ribosyltransferases (ARTDs; previously referred as poly-ADP-ribose polymerases or PARPs) and the removal ADPr catalyzed family glycohydrolases. Although thousands potential modification sites have been identified using high-throughput mass-spectrometry, relatively little known about sequence specificity encoded near site. Herein, we present...
Transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) to target proteins is mediated by a class human poly-ADP-ribose polymerases, PARPs, and removal ADPr catalyzed family glycohydrolases. Although thousands potential modification sites have been identified using high-throughput mass-spectrometry, relatively little known about sequence specificity encoded near the site. Herein, we present matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method that...
Metal ions are important co-factors in RNA stabilization, folding and catalysis. In each of these roles, it is expected that the number type interactions between metal lead to a particular thermodynamic value. The crystal structure trans-activating response (TAR) element HIV-1 shows inner-sphere with three calcium at trinucleotide bulge region. Thus, can be used as model measure contributions for specific metal-RNA interactions. Using thermal denaturation experiments we show magnesium...
Poly (ADP‐ribose) polymerases, PARPs, are a family of 17 enzymes (in humans) that catalyze the transfer ADP‐ribose onto target proteins from nicotinamide adenine dinucleotide (NAD + ). ADP‐ribosylation occurs in highly conserved PARP catalytic domain found all seventeen PARPs. Significant effort using modern proteomic methods has led to identification thousands potential targets cell. Unfortunately, this analysis not yet uncovered which sites preferentially targeted vivo nor determinants for...