RESEARCH PROGRAMS

From genetic code to neural circuits to metabolic health

We investigate how the hypothalamus develops, interprets internal signals, and adapts to medicines and the environment. Our goal is to explain why appetite control fails and identify precise ways to restore it.

OUR RESEARCH FRAMEWORK

Start with a human problem

Childhood obesity or antipsychotics' metabolic effects

Define the mechanism

Genes, cell fate, receptors, channels, and circuits

Test the physiology

Feeding, energy balance, and behavior

Find a therapeutic opening

A precise point where harmful biology may be interrupted

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01 GENES & DEVELOPMENT

02 MEDICINES & METABOLISM

03 CIRCUITS & BEHAVIOR

Why do rare genetic variants cause severe childhood obesity?

A small change in DNA can alter how the hypothalamus develops, how appetite signals are interpreted, and how the body maintains energy balance throughout life.

01 GENES & DEVELOPMENT

Why do rare genetic variants cause severe childhood obesity?

Human genetics

CRISPR models

Single-cell multiome

We recreate human variants in mice, map cell-state changes with single-cell transcriptomic and multiomic methods, and connect molecular changes to neural activity, feeding, glucose control, and susceptibility to diet-induced obesity.

Neural development

Metabolic physiology

Children with rare obesity-associated variants can develop extreme hunger and rapid weight gain early in life. Understanding the causal biology is essential for moving from a genetic diagnosis to a mechanism-based treatment.

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PROGRAM 01

WHY IT MATTERS

HOW WE STUDY IT

WHAT WE ARE LEARNING

Our studies identify developmental regulators, including OTP, that establish and maintain melanocortin neuron identity. This work shows how early changes in neural identity can reshape adult metabolic risk.

Orthopedia regulates Melanocortin 4 Receptor transcription and energy homeostasis. Sci Transl Med.

Developmental reprogramming in melanocortin neurons modulates diet-induced obesity in mice. Neuron

Comparative transcriptomic analyses of developing melanocortin neurons reveal new regulators for the anorexigenic neuron identity. J Neurosci.

Why do antipsychotic drugs disrupt appetite control?

Antipsychotic medicines can be life-changing, yet some also produce intense hunger, rapid weight gain, and diabetes risk. We investigate where psychiatric treatment and metabolic biology intersect.

02 MEDICINES & METABOLISM

Why do antipsychotic drugs disrupt appetite control?

MC4R signaling

Fiber photometry

Drug-induced obesity models

We combine clinically relevant dietary drug exposure, engineered mouse models, fiber photometry, metabolic phenotyping, receptor pharmacology, and electrophysiology to trace drug action from molecular signaling to feeding behavior.

Electrophysiology

These metabolic side effects can compromise long-term health and contribute to treatment discontinuation. The goal is not to replace psychiatric therapy, but to preserve its benefits while protecting long-term metabolic health.

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PROGRAM 02

WHY IT MATTERS

HOW WE STUDY IT

WHAT WE ARE LEARNING

Our work identifies the MC4R–Kir7.1 signaling partnership as an important convergence point for clozapine-induced hyperphagia and weight gain, revealing a potential path toward mechanism-based protection.

The atypical antipsychotic risperidone targets hypothalamic melanocortin 4 receptors to cause weight gain. J Exp Med.

Functional coupling between MC4R and Kir7.1 contributes to clozapine-induced weight gain in female mice. Nat Commun.

The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C. J Clin Invest.

Which serotonin circuits can suppress appetite safely?

Serotonin can reduce food intake, but raising serotonin throughout the body can also cause serious adverse effects. The challenge is to isolate the beneficial circuit from the harmful ones.

03 CIRCUITS & BEHAVIOR

Which serotonin circuits can suppress appetite safely?

Receptor genetics

Circuit mapping

Calcium imaging

We use receptor-specific genetics, intersectional circuit mapping, in vivo neural recording, chemogenetic and pharmacological perturbations, and quantitative feeding assays to define the responsible cells and pathways.

Spatial transcriptomics

Feeding behavior

Past serotonin-based weight-loss therapies showed that appetite can be suppressed, but widespread serotonergic activation also produced unacceptable risk. Circuit-level precision may allow us to retain appetite suppression without globally activating the serotonin system.

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PROGRAM 03

WHY IT MATTERS

HOW WE STUDY IT

WHAT WE ARE LEARNING

We identified a serotonin 1B receptor circuit that suppresses appetite by acting through hypothalamic AgRP neurons, helping separate a specific feeding pathway from serotonin’s broader physiological actions.