Injuries to the brain or spinal cord can be devastating, seriously affecting how someone moves, feels, and thinks. The Smith Lab studies ways to help the body heal after these kinds of injuries. We investigate how gene therapy promotes recovery by enhancing axonal plasticity within sensory and motor systems.  

Ongoing projects include: 

• Finding out how brain and spinal cord nerve circuits change during physical therapy after a spinal injury. 
• Rebuilding lost nerve connections by transplanting new nerve cells and directing their growth using gene therapy. 
• Inducing  regeneration of sensory nerve axons into the spinal cord. 
• Studying how energy-producing parts of nerve cells (called mitochondria) are affected by injury. 

 We are particularly interested in augmenting neural circuitry involved in motor learning and memory to recover function following rehabilitation.  

Our novel techniques include intersectional genetics for functional circuit mapping, kinematic analyses of movement patterns, gene therapy using viral vectors, electrophysiology, and behavioral analyses.

We focus on the genetic and molecular changes in the brain caused by Fetal Alcohol Spectrum Disorders (FASD) — a group of conditions that happen when a mother drinks alcohol during pregnancy.   

In collaboration with Dr. Michal Seltzer 
In collaboration with Dr. Michael Selzer’s lab, the Darbinian lab is studying tiny particles called exosomes. These indicate activity involved in brain cells such as neurons, oligodendrocytes, microglia, astrocytes, as well as synaptic proteins, and signaling molecules called cytokines/chemokines. Since exosomes can travel into the mother’s blood, they may allow doctors to detect brain changes related to FASD in a fetus using just a blood sample from the pregnant mother—without touching the baby. 

We are also, in collaboration with Dr. Selzer’s lab and the Department of OB/GYN, doing clinical studies to determine how neuronal and oligodendrocyte loss is caused in FASD. 

Axons are the “cables” that connect brain cells and help them send signals to each other. The Gallo laboratory investigates how axons grow, heal, and respond to injury. 

One aspect of our research seeks to learn how axons use ATP for energy. We study how different ways of making ATP — either in the mitochondria or through a process called glycolysis — affect how axons grow and repair themselves. 

• Another focus is on the axon’s cytoskeleton. This is the inner structure that shapes the cell and helps it function. We are interested in how certain signals inside the cell’s inner structure affect the axon’s shape and behavior.  

By combining these studies, we seek to understand how energy use, cell structure, and signals work together to keep axons healthy and working properly.

A significant portion of the central nervous system (CNS) cells are made up of non-neuronal cells known as glia. We study a specific type of glial cells called oligodendrocytes to understand how their dysfunctions contribute to Alzheimer's disease and other CNS disorders. 

Oligodendrocytes form myelin, a protective coating that helps brain cells send signals quickly. In diseases like Alzheimer’s disease, brain inflammation and toxic cell environments alter oligodendrocytes. By identifying these abnormalities, we aim to find improved methods to repair the damage. 

We also explore the potential of oligodendrocyte progenitor cells (OPCs), which can turn into healthy oligodendrocytes, to better restore CNS myelin.   

Our ultimate goal is to discover how to leverage these cells to repair the brain. 

We use a range of advanced tools, including: 

• Genetically engineered mice to study loss or gain of function.  
• AAV-mediated gene delivery or gene knock-down targeting oligodendrocytes 
• In vivo genetic fate tracing of oligodendrocyte progenotors.  
• Next-generation single-cell sequencing. 

Learning how these cells work and change can lead to new treatment for brain diseases using the brain’s ability to heal itself.  

Our lab studies how the brain develops and what happens when that process goes wrong. Abnormal brain development underlies neurological/psychiatric disorders such as intellectual disability, seizures, autism, and schizophrenia. We focus on neural progenitor cells, which produce cells that make up the brain, such as neurons and glial cells. We want to understand how these cells grow, divide, and differentiate into other types of brain cells.  When this process doesn’t work properly, it can lead to brain malformations, including microcephaly (a small brain), hydrocephalus (fluid buildup in the brain), and periventricular heterotopia (misplaced brain cells).   We have generated several mouse and human brain organoid models that help us study the mechanisms of developmental brain disorders. In particular, we have found strong genetic interactions between polarity-determining genes and mitogenic/growth signals.  

 Cutting-edge techniques our lab utilizes include:  

• In-utero manipulation to test hypotheses in vivo.  
• Brain organoid (“mini-brain”) systems made from Induced Pluripotent Stem Cells (iPSC).  
• Extensive gene expression profiling, such as single-cell transcriptomics for understanding fundamental molecular mechanisms.  
• Time-lapse imaging for monitoring cellular changes.  
• 3-D reconstruction of brain cells after high-resolution imaging.  

By learning how brain cells are produced and changed, we hope to find new ways to treat or prevent brain birth defects.

We’re investigating neural tube defects (NTDs) — problems that happen when the brain and spinal cord don’t form correctly during early development. We’re focusing on myelomeningocele (MMC), a serious type of spina bifida where the spinal cord is damaged and exposed, often leading to lifelong disabilities. 

In particular, our research includes: 

• Fetal rat models that closely mimic human MMC. These help us understand how the spinal cord develops abnormally. 
• Studying why spinal cord cells called astrocytes form in unusual ways during MMC.  
• How changes in cell signals and gene activity affect neural progenitor cells that form critical sensory and motor function circuits. 
• Learning how the uterine environment affects the exposed developing spinal cord. 
• Examining amniotic fluid to identify changes (biomarkers) linked to MMC.  
• Our goal is to improve early diagnosis and care for babies with these disorders.  

When the brain, spinal cord, or other areas of the Central Nervous System (CNS) sustain injuries or are affected by diseases, nerve cells can die, and their connections, known as axons, may break. As a result, individuals often experience long-term issues with movement, sensation, cognition, and other bodily functions. Unfortunately, there are currently no effective treatments available to help nerves heal or regrow. 

Our laboratory investigates why damaged nerve cells fail to regenerate. We aim to discover new methods to assist the brain and spinal cord in recovering from traumatic injuries, strokes, multiple sclerosis, and other disorders. 

Our research involves: 

• Studying how receptor proteins on the cell membrane prevent axons from growing when scar tissue forms. 
• Exploring how signals within neurons influence growth, particularly as the cells age. Because the transmembrane receptors partly mediate the growth suppression of mature neurons, these receptors may become molecular targets for developing a treatment. 
• Developing new therapeutic strategies, such as small antagonist peptide drugs that may aid in treating damaged nerves, and specialized recombinant viruses that can deliver beneficial genes to targeted nerve cells. 
• Our ultimate goal is to identify treatments that not only keep injured nerves alive but also promote their regrowth afterward. 

Our goal is to discover treatments that keep injured nerves alive and help them grow back afterwards.  

Dr. Selzer’s lab has a long history of performing studies on how nerve fibers (axons) can regrow after spinal cord injury and on the scientific basis of neurological rehabilitation. We use a simple animal called a sea lamprey to help understand how this process works at the cell and molecular level. More recently, the team has focused on the role of maternal substance use in causing disorders of brain development, including Fetal Alcohol Spectrum Disorders (FASD), the most common preventable cause of childhood disability.  This group of disabilities results when the mother drinks alcohol during pregnancy.  

In collaboration with Dr. Nune Darbinian’s lab, the Selzer lab is studying tiny particles called exosomes. These indicate activity involved in brain cells such as neurons, oligodendrocytes, microglia, astrocytes, as well as synaptic proteins, and signaling molecules called cytokines/chemokines. Since exosomes can travel into the mother’s blood, they may allow doctors to detect brain changes related to FASD in a fetus using just a blood sample from the pregnant mother—without touching the baby.  Moreover, if this approach is successful in FASD, it also could be used in brain disorders associated with maternal exposure to other drugs or environmental factors.

We're working on ways to fix damaged nerves between the spine and the muscles or skin, which could help people move and feel again after nerve or spinal cord injuries. To study this, we use mice with similar injuries and focus on two types of support cells—OPCs and Schwann cells. 

One part of our research looks at why some nerves can’t grow back into the spinal cord after injury. We think OPCs might be getting in the way, so we’re testing treatments that could help these nerves grow back and reconnect properly. 

Another part of our work focuses on Schwann cells, which help keep nerves healthy and repair them when they’re damaged. We're studying specific proteins in these cells, like YAP and TAZ, to understand their role in nerve repair and even tumor growth. 

• We use advanced technology like special mouse genetics, high-tech imaging and gene therapy to find treatments that could one day help real patients. 

The Thomas lab studies why and how axons — the long, thin parts of nerve cells — break down or are damaged. 

Nerve cells use their axons to carry signals within the brain, as well as to and from other parts of the body, such as the spinal cord, other organs and peripheral tissues. Some human axons can be a meter long, but only 1 micron wide. These long and delicate structures are easily damaged by injuries or diseases. 

Our team is especially interested in how certain proteins help protect or harm axons. We discovered a fat molecule called palmitate that can attach to these proteins like a sticky tag. This tag helps send proteins to the right place inside the axon.  

We are studying how blocking or increasing this “tagging” process changes the way axons break down. Our goal is to see if this could lead to new treatments that protect axons and slow down nerve damage caused by injury or disease.

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