Neuroscience · Temple University
Research
My dissertation asks two questions: what do descending serotonergic circuits actually do, and can we rebuild them after spinal cord injury?
Overview
Spinal cord injury eliminates the descending supraspinal input that motor circuits need to produce coordinated movement. Among the most consequential of these inputs are serotonergic projections from the caudal raphe nuclei (CRN) — a cluster of brainstem nuclei whose raphespinal axons modulate spinal interneurons and motoneurons across the full length of the cord.
Despite decades of research implicating raphe serotonin in locomotor recovery, the functional contributions of distinct CRN subnuclei remain almost entirely unresolved. We don't know what raphe magnus, obscurus, and pallidus each contribute — independently or in parallel — to normal locomotion, or how those contributions change after injury. My thesis is designed to answer that.
Aim 1 — Circuit dissection
Subnucleus-specific chemogenetic dissection of caudal raphe serotonergic projections
Using Tph2-iCre rats and Cre-dependent viral vectors, I selectively express bidirectional DREADDs — excitatory hM3Dq and inhibitory KORD — in serotonergic neurons of individual CRN subnuclei (raphe magnus, obscurus, and pallidus). This gives me chemogenetic control over specific serotonergic populations both before and after thoracic contusion SCI.
To quantify the behavioral output of each manipulation, I use a high-dimensional kinematics pipeline built on DeepLabCut and demixed principal component analysis (dPCA). Rather than collapsing locomotion into coarse summary scores, this approach resolves interlimb coordination, gait transitions, joint angle trajectories, and fatigue-related kinematic drift — variables that are sensitive to graded neuromodulatory changes and can distinguish subnucleus-specific phenotypes.
The overarching hypothesis is that CRN subnuclei are not functionally redundant — that each exerts a distinct, measurable influence on locomotor kinematics, and that these contributions can be individually targeted to improve recovery after SCI.
Aim 2 — Regenerative strategy
iPSC-derived serotonergic organoid transplantation as a neuromodulatory replacement strategy after SCI
Aim 2 takes the circuit knowledge from Aim 1 and asks: if we know what serotonergic input the injured cord is missing, can we replace it? I differentiate human induced pluripotent stem cells (iPSCs) into serotonergic neurons using a hindbrain-directed protocol, organizing them as three-dimensional brain organoids — a format that better recapitulates the cytoarchitecture of endogenous raphe nuclei compared to monolayer cultures.
These organoids are engineered with excitatory DREADDs prior to transplantation, enabling controlled chemogenetic activation of the graft after it's in place. This is the key design feature: rather than transplanting cells and hoping they integrate appropriately, DREADD-enabled activity control allows us to drive the graft's output at defined timepoints and dose it like a pharmacological intervention.
Transplants are delivered to the injury site in SCI rats, and outcomes are assessed across survival, integration, axon growth, 5-HT reinnervation of spinal targets, and — where possible — functional recovery on the same kinematic battery used in Aim 1.
Affiliations
Dr. George Smith, Ph.D.
Primary advisor
In vivo systems neuroscience — viral engineering, stereotactic surgery, chemogenetics, SCI models.
Dr. Seonhee Kim, Ph.D.
Co-advisor
Stem cell biology and organoid engineering — iPSC differentiation, 5-HT lineage specification, in vitro validation.
Dr. Andrew Spence, Ph.D.
Co-advisor
Kinematics and computational modeling — DeepLabCut, biomechanical analysis, dimensionality reduction.
Temple University
Biomedical Sciences PhD — Neuroscience concentration
Lewis Katz School of Medicine. Third year.
Funding
F31 predoctoral fellowship application submitted April 2026 — NINDS. Covers the bidirectional DREADD + quantitative kinematics design across both aims.
Presentations
Presenting author marked with *.
- 2024
Yap is required for neuroepithelium and cortical layer development.
Human Development & 3D Brain Modeling, Cold Spring Harbor, NY, USA.
- 2024
Yap is required for neuroepithelium and cortical layer development.
23rd Annual Dawn Marks Research Day, Temple University, Philadelphia, PA, USA.
- 2024
Genetic method to selectively lesion axons or prune axonal terminals.
Society for Neuroscience 2024, Chicago, IL, USA.
- 2022
Cannabinoid Receptor Interacting Protein 1a (CRIP1a): Function as a Gαi Carrier.
32nd Annual Symposium on the Cannabinoids, International Cannabinoid Research Society, Galway, Ireland.
- 2022
Giα and β Proteins Associate in a Complex with Cannabinoid Receptor Interacting Protein 1a (CRIP1a).
Experimental Biology 2022, Philadelphia, PA, USA.
- 2021
CRIP1a exhibits differential binding with G protein subtypes.
Wake Forest University Undergraduate Research Day, Winston-Salem, NC, USA.
Long-term goals
My dissertation is one node in a longer trajectory. The endpoint is a lab built around the human–machine interface — closed-loop AI systems running in vivo experiments, robotic organoid culture, and prosthetic development under one roof, with physical disability as the primary target.
Spinal injury, blindness, motor loss after stroke or neurodegeneration: the nervous system retains far more capacity for repair and reorganization than clinical practice currently exploits. The tools to unlock it — chemogenetics, iPSC-derived grafts, high-dimensional behavioral readouts, AI-driven experimental loops — already exist in isolation. My contributions are in the assembly: integrating them into a research environment that compounds, so the rate at which we move from circuit insight to restored function is no longer rate-limited by the lab itself.
The shorter version: build the tooling, train the scientists, and shorten the distance between a broken nervous system and a working one. Folks shouldn't have to go blind forever.