Rebecca P. Seal, PhD

Decoding the Spinal Cord's Role in Pain: From Molecules to Therapeutics. 

Pain affects millions worldwide, yet effective treatments remain elusive. Our laboratory tackles the challenge of chronic pain by investigating how the dorsal horn of the spinal cord, the body's first relay station for pain signals, generates and sustains both acute and chronic pain states. Using state-of-the-art multiomics, spatial transcriptomics, and gene regulatory network analyses, we're creating the first truly integrated atlas of spinal cord neuron subtypes that spans from mice to humans. This cross-species perspective reveals which pain circuits are fundamentally conserved and therefore most likely to translate into effective human therapies. 

We employ chemogenetic, pharmacological and circuit tracing techniques to causally identify the neuron subtypes underlying chronic pain. And we use targeted proteomic approaches together with electrophysiology to study the protein-level changes within these critical neuron subtypes. The overall goal of our cross-species strategy is to identify key human circuits and mechanisms for chronic pain using rodents and nonhuman primates for causal studies. By combining evolutionary conservation across species, causal validation through manipulation, and molecular precision in identifying therapeutic targets, we're building a translational pipeline designed to overcome the historical challenge of moving pain research from the laboratory to the clinic.

To execute this plan, we are working closely with leading human, NHP, and bioinformatics laboratories including Dr. Andreas Pfenning's group at Carnegie Mellon University, and Drs. David Schaeffer’s, Hans Mathys’ and Holden Ko's laboratories at the University of Pittsburgh as well as spine surgeons in the Department of Neurosurgery at UPMC.

Neural Circuits Controlling Movement in Parkinson's Disease 

Parkinson's disease affects over 10 million people worldwide and is due to the progressive loss of dopamine neurons in the substantia nigra. Motor symptoms often appear when 60-70% of these neurons are lost. While efforts to protect dopamine neurons gets at the root cause, the delay or amelioration of motor symptoms could substantially improve quality of life and potentially save lives? Our laboratory has discovered a method to delay the onset of motor deficits in a model of PD on the order of months, and we are working to identify the molecular mechanisms with the long-term goal of using this new understanding to prolong- potentially maintain indefinitely normal motor function in human PD.

We're decoding this resilience at multiple scales. Using proteomics, we are identifying the molecular signatures that distinguish compensated from decompensated states. Through rabies tracing and functional circuit mapping, we are revealing how basal ganglia connectivity patterns rewire during the pre-symptomatic phase. With in vivo calcium imaging in behaving animals, we capture how striatal activity patterns evolve in real-time as dopamine depletes but movement remains intact. Finally, using DREADDs, we're directly testing whether the cellular and circuit adaptations we observe are necessary and sufficient for preserved motor function—moving from understanding to intervention.

Current PD therapies address symptoms after they emerge but don't target the brain's natural resilience mechanisms. Our work reveals an entirely different therapeutic opportunity: understanding and amplifying the compensatory plasticity that naturally delays symptom onset. If we can sustain or enhance these protective adaptations, we might keep patients symptom-free for years longer, or even indefinitely. We collaborate closely with Dr. Mac Hooks' laboratory at the University of Pittsburgh to tackle these questions from multiple angles.

Join Us. We are looking for creative, driven graduate students and postdoctoral fellows who are excited about working at the intersection of molecular biology, systems neuroscience, and translational medicine. You'll learn cutting-edge techniques including multiomics, proteomics, chemogenetics, viral tracing, functional circuit mapping while contributing to research with direct clinical impact. Studies of sensory and motor circuits in health and disease.