Ongoing Projects

Research

Our group aims to implement meaningful discoveries in basic biology to help drive clinical applications and treatments.

The broad goal of our research is to understand the mechanisms underlying the bidirectional relationships between sleep, circadian rhythms, and psychiatric disorders.

We investigate the molecular and cellular mechanisms within neural circuits of the midbrain, striatum, and prefrontal cortex that mediate the impact of sleep and/or circadian rhythm disruption on motivation and reward. We also study the impact of drug use on sleep and circadian rhythms in the brain and body. Using both human cells and tissues, along with rodent models of disease, we built a robust experimental and analytical pipeline for discovering and validating novel mechanisms of mood and substance use disorders, with the ultimate goal of developing new treatments. 

At the core of our research program are a unique combination of approaches and techniques that investigate multiple biological scales from genes to behavior. We leverage various tools in genomics, transcriptomics and proteomics, and integrative, cross-species (human, non-human primate, and rodent) approaches in computational biology, in combination with genomic editing, gene targeting, neural circuit imaging, and complex behavioral assays in animal models of psychiatric disorders. 

By integrating these approaches, our group seeks to uncover the complex mechanisms that underlie co-occurring mood and substance use disorders. Our multi-disciplinary research promises to advance our understanding of these disorders and pave the way for novel, effective treatments that could transform the lives of patients.

Molecular rhythms in cognitive and reward neural circuits

Elucidating the functional role of molecular clocks in specific cell types within brain regions involved in cognition, motivation, and reward.

Disrupted sleep and circadian rhythms in psychiatric disorders

Investigating the bidirectional relationships between sleep and circadian rhythms and their roles in the vulnerability to and progression of psychiatric disorders.

Molecular and cellular mechanisms of substance use disorders

Using both human tissues and rodent models to uncover new mechanisms of addiction.

Chronic stress and vulnerability to mood and substance use disorders

Further understanding the role of stress as a major risk factor for depression, bipolar, and substance use disorders

Ongoing Projects

Our lab aims to implement meaningful discoveries in basic biology to help drive novel clinical outcomes.

Molecular rhythms in cognitive and reward neural circuits

Our laboratory is systematically investigating the functional roles of molecular clocks in specific neural cell types across different brain regions involved in cognition, motivation, and reward.

Circadian rhythms are near 24-hour oscillations found in essentially every physiological process in the brain and body. In cells, molecular rhythms are generated by a series of transcriptional-translational feedback loops involving transcriptional activators controlling the expression of many genes in a circadian manner. Many of these “clock-controlled” genes are tissue- and cell type-dependent, important for optimal physiology, behavior, and ultimately, health. We use several strategies, including viral-mediated gene transfer, CRISPR, and gene editing, to target circadian genes in specific cell types in the mouse brain. By controlling the expression of circadian genes in neural cell types, we can then investigate their roles in neural physiology and behavior related to motivation, anhedonia, and reward.

Disrupted sleep and circadian rhythms in psychiatric disorders

vulnerability of developing several psychiatric disorders, including depression, bipolar, and substance use. Psychiatric disorders are associated with severe and persistent sleep and circadian disruptions, often leading to worsening of symptoms and elevating disease severity.

Sleep disruptions and circadian dysfunctions are observed in several brain disorders, typically emerging at different stages of life. For example, sleep and circadian dysfunction are associated with neurodevelopmental disorders, such as ADHD, autism, among others. Other disorders emerging during adolescence and young adulthood are also associated with sleep and circadian dysfunction, including substance use disorders, depression, and bipolar disorder. Our laboratory uses both human tissues and rodent models to further understand the contributions of sleep and circadian dysfunction to the development and progression of psychiatric disorders across the lifespan.

Molecular and cellular mechanisms of substance use disorders

Our laboratory has substantial efforts in identifying and understanding the molecular and cellular substrates of addiction using integrative cross-species approaches between humans and rodent models.

Prevalence rates of substance use disorders continue to rise in the United States. Rates of opioid use and diagnoses of opioid use disorder, in particular, have increased dramatically, accompanied by a surge of overdose deaths. An understanding of the biological alterations that occur in the brains of people who suffer from opioid use disorder remains limited. Our laboratory has major efforts in studying the molecular and cellular alterations in human postmortem brains from subjects with opioid use disorder, leveraging proteomics, transcriptomics, and single cell technologies. We are actively developing custom computational pipelines to integrate findings across humans and rodents to highlight novel mechanisms of opioid use disorder and co-occuring mood disorders.

Chronic stress and vulnerability to mood and substance use disorders

diseases, including depression, bipolar, and substance use disorders.

Our laboratory uses various stress models in rodents to recapitulate the impact of chronic stress on body physiology and behaviors associated with mood and substance use disorders. Several avenues of research examine the impact of chronic stress on sleep and circadian rhythms in the brain and peripheral tissues, such as liver and immune system. Other projects include new ventures into hoarding disorder and compulsive behaviors.