Research

Understanding the molecular and circuit-specific mechanisms underlying depression and addiction through cutting-edge neuroscience approaches.

Depression Circuits

R01MH128192

Our lab investigates how chronic stress leads to depression by studying the neural circuits connecting the prefrontal cortex to the nucleus accumbens. We discovered that Shisa6, a gene that regulates AMPA receptor function, is specifically altered in D1-type medium spiny neurons of susceptible individuals.

Prefrontal-accumbens circuit dysfunction in social stress
Cell-type specific transcriptomics (D1 vs D2 MSNs)
Shisa6 as a novel depression-related gene
SIRT1 signaling in nucleus accumbens

Addiction Mechanisms

ABRC Investigator Grant

We study how drugs of abuse, particularly cocaine, alter the epigenetic landscape of reward circuits. Our work on SIRT1, a histone deacetylase, revealed its essential role in cocaine and morphine action in the nucleus accumbens.

SIRT1-FOXO3a signaling in drug reward
Cell-type specific epigenetic changes
Circadian clock regulation of addiction
Tet1 and 5-hydroxymethylcytosine in cocaine action

Synaptic Tools Development

Patent WO2023212664A1

We are developing novel technologies to manipulate and map synaptic connections with unprecedented precision. Our "synapse surgery" tools allow for circuit-specific synapse ablation and modification.

STAPL-Ex proximity labeling
Split-TurboID for synaptic proteomics
mGRASP synaptic connectivity mapping
Novel circuit manipulation techniques

Translational Approaches

Salk Institute & NIMH Collaborations

To bridge preclinical findings to human disease, we utilize iPSC-derived brain organoids from MDD patients. Collaborations with the Gage lab (Salk) and NIMH provide access to unique patient-derived cell lines.

MDD patient-derived iPSC lines (SSRI responder/non-responder)
AMBiGen iPSC resource (16p11.2 CNV carriers)
Brain organoid disease modeling
Drug screening platforms

Our Toolkit

We have established 19 unique transgenic mouse lines and employ state-of-the-art techniques for circuit-specific interrogation.

Cell-type specific RNA-seq (RiboTag)
Fiber Photometry
Optogenetics
CRISPR/Cas9 Epigenetic Remodeling
Single-cell RNA-seq
Spatial Transcriptomics (Visium HD, Xenium)
Proximity Labeling (split-TurboID)
iPSC-derived Brain Organoids