A5046791936- Neurotransmitter Receptor Influence on Behavior
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- Adipose Tissue and Metabolism
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Biochemical Analysis and Sensing Techniques
- Tryptophan and brain disorders
- Nicotinic Acetylcholine Receptors Study
- Regulation of Appetite and Obesity
- Genetics and Neurodevelopmental Disorders
- Redox biology and oxidative stress
- RNA Interference and Gene Delivery
- Stress Responses and Cortisol
- Epigenetics and DNA Methylation
- Behavioral Health and Interventions
- Neuropeptides and Animal Physiology
- Click Chemistry and Applications
- Memory and Neural Mechanisms
- Decision-Making and Behavioral Economics
- Neurogenesis and neuroplasticity mechanisms
- Chemical Synthesis and Reactions
- RNA and protein synthesis mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
University of California, San Diego
2019-2025
UC San Diego Health System
2023
Ghent University Hospital
2015-2021
Scripps Research Institute
2019-2020
Ghent University
2010-2018
Massachusetts General Hospital
2015-2018
Harvard University
2015-2018
Howard Hughes Medical Institute
2016-2018
Another link in the chain: A thiolactone-based approach for preparation of multifunctionalized sequence-defined oligomeric structures on solid support was established. The iterative aminolysis/chain extension method with a single building block and variety commercial amines allowed protecting group free synthesis various motifs unique backbone preprogrammed organization side chain functionalities. As service to our authors readers, this journal provides supporting information supplied by...
Significance The X-chromosome harbors hundreds of disease genes, a subset which gives rise to neurodevelopmental disorders such as Rett syndrome (RTT), fragile X syndrome, and CDKL5 syndrome. There is presently no disease-specific treatment. Here, we work toward therapeutic program based on reactivation the silent chromosome restore expression missing protein. We develop mixed modality approach that combines small-molecule inhibitor DNA methylation an antisense oligonucleotide against Xist...
Significance More than 2 million individuals in the United States currently have a substance use disorder that is related to prescription opioid pain relievers. We identified individual differences oxycodone addiction-like behaviors outbred heterogenous stock rats with high and low behaviors. found downregulation of nociceptin levels central nucleus amygdala (CeA) may be responsible for hyper–γ-aminobutyric acid (GABA)ergic tone CeA observed who develop The development small molecules target...
Abstract The amygdala processes positive and negative valence contributes to addiction, but the cell-type-specific gene regulatory programs involved are unknown. We generated an atlas of single-nucleus expression chromatin accessibility in outbred rats with high low cocaine addiction-like behaviors following prolonged abstinence. Differentially expressed genes between groups were enriched for energy metabolism across cell types. Rats addiction index (AI) showed increased relapse-like...
The coming of age story furan oxidation cross-linking.
An einem festen Träger werden über einen Thiolacton-basierten Syntheseansatz multifunktionalisierte sequenzdefinierte Oligomerstrukturen aufgebaut. Durch die iterative Aminolyse/Kettenverlängerung mit einzigen Baustein und vielen kommerziell verfügbaren Aminen gelingt schutzgruppenfreie Synthese verschiedener Oligomermotive vorprogrammierter Organisation der Seitenkettenfunktionalitäten. As a service to our authors and readers, this journal provides supporting information supplied by the...
Significance Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in MECP2 . To treat RTT, reactivating the dormant copy of on inactive X has been considerable interest. Although potential therapeutics have identified, their development hampered lack a suitable female mouse model and uncertainty regarding how much needs to be restored. Here, we create with more severe phenotype, including short lifespan, neuromotor impairment, repetitive behaviors often seen...
Significance In mammalian female cells, nearly all genes are silenced on one of two X chromosomes. Heterozygous females with “dominant” X-linked diseases, such as Rett syndrome, may benefit from pharmacological reactivation the silent, healthy allele in affected organs. Toward establishing proof concept, here we carry out a primed screen large library small molecules for compounds that can reactivate expression inactive (Xi). We identify combination inhibits DNA methylation and Aurora kinase...
Substance abuse and addiction represent a significant public health problem that impacts multiple dimensions of society, including healthcare, the economy, workforce. In 2021, over 100,000 drug overdose deaths were reported in US, with an alarming increase fatalities related to opioids psychostimulants. Understanding fundamental gene regulatory mechanisms underlying behaviors could facilitate more effective treatments. To explore how repeated exposure alters networks brain, we combined...
Background: Oxycodone has an elevated abuse liability profile compared to other prescription opioid medications. However, many human and rodent metabolomics studies have not been specifically focused on oxycodone. Objectives: Investigating changes associated with oxycodone exposure can provide insights into biochemical mechanisms of the addiction cycle prognosis prediction. Methods: Plasma samples from 16 rats at pre-exposure intoxication time points were profiled Metabolon platform. A total...
Hormonal fluctuations throughout the estrous cycle have been hypothesized to influence drug-related behaviors. Preclinical models show that some cocaine-related behaviors are influenced by cycle. However, extent which modulates cocaine self-administration in outbred heterogeneous stock (HS) rats, a population captures human genetic diversity, is unknown. This study aimed examine relationship between phases and behavior HS rats using model of extended access self-administration. We focused on...
We here report on the furan oxidation methodology for interstrand cross-linking of RNA duplexes, which have a different structure and are more stiff, reactive labile than their DNA counterparts. Through this mildly inducible approach, natural unmodified can be selectively cross-linked in high yield. The method therefore has direct applications increasing number based technologies.
A cross-linking methodology for the study of DNA-protein interactions is described. The method inspired by metabolic activation furans causing toxic DNA damage, including cross-links (DPC). furan moiety, representing a latent functionality, easily incorporated into oligonucleotides, and can be activated on demand to release reactive aldehyde. Reaction with nucleophilic lysine side chains shown distance-sensitive allows site-selective DPC formation.
Cocaine affects food intake, metabolism and bodyweight. It has been hypothesized that feeding hormones like leptin play a role in this process. Preclinical studies have shown mutually inhibitory relationship between cocaine, with also decreasing the rewarding effects of cocaine intake. But prior used relatively small sample sizes did not investigate individual differences genetically heterogeneous populations. Here, we examined whether bodyweight blood level are associated high or low...
Anxiety is a critical component of the development and maintenance drug addiction; however, anti-anxiety medications such as benzodiazepines beta-blockers (β-adrenergic receptor antagonists) are not used for treatment substance use disorder, except management acute withdrawal syndrome. Preclinical studies have shown that may reduce stress-induced relapse; effect beta blockers on escalation intake has been tested. To address this issue, we chronically administered β-adrenergic antagonist...
Chronic nicotine results in dependence with withdrawal symptoms on discontinuation of use, through desensitization nicotinic acetylcholine receptors and altered cholinergic neurotransmission. Nicotine is associated increased whole-brain functional connectivity decreased network modularity; however, the role neurons those changes unknown. To identify contribution regions to network, we analyzed main brain-wide activation immediate early-gene Fos during male mice correlated these expression...
Nicotine use produces psychoactive effects, and chronic is associated with physiological psychological symptoms of addiction. However, nicotine known to decrease food intake body weight gain, suggesting that also affects central metabolic appetite regulation. We recently showed acute self-administration in nicotine-dependent animals a short-term increase intake, contrary its long-term feeding behavior. As behavior regulated by complex neural signaling mechanisms, this study aimed test the...
Addiction is commonly characterized by escalation of drug intake, compulsive seeking, and continued use despite harmful consequences. However, the factors contributing to transition from moderate these problematic patterns remain unclear, particularly regarding role sex. Many preclinical studies have been limited small sample sizes, low genetic diversity, restricted access, making it challenging model significant levels intoxication or dependence translate findings humans. To address...
Abstract A dipodal peptidosteroid based on a deoxycholic acid scaffold was designed as transcription factor model to study, and ultimately interfere in, selective protein–DNA interactions. In this paper, the binding of such its DNA site is described for first time, thus proving concept confirming potential design. To achieve this, two 25‐mer peptides were synthesized in parallel close proximity rigid amphiphilic scaffold, attached by flexible linkers. Peptide aggregation complicated...
Abstract The development of straightforward and versatile peptide cyclisation methods is highly desired to meet the demand for more stable peptide‐based drugs. Herein, a new method synthesis side‐chain‐to‐tail cyclic peptides with simultaneous introduction an N‐terminal handle, based on thiolactone building block, described. A primary amine liberates homocysteine analogue from which further enables through disulfide‐bond formation C‐terminal cysteamine. Postcyclisation modification can be...
Abstract Genome-wide association studies typically evaluate the autosomes and sometimes X Chromosome, but seldom consider Y or mitochondrial (MT) Chromosomes. We genotyped MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. identified distinct 4 among founders. However, only 2 types of each nonrecombinant chromosome were observed our modern HS rat (generations 81–97). Despite relatively large sample size, there virtually...