
Assistant Professor of Pediatrics
Assistant Professor in Neurology
Member of the Duke Cancer Institute
About Us
The mission of the Russ lab is to advance our understanding about how specific neurons in the cerebral cortex are altered in perinatal brain injury and genetic neurodevelopmental disorders, and then to use this information to identify new molecular targets to treat these disorders.
Perinatal Brain Injury
The day of your life where you are most at risk of having a stroke is the day that you are born. Hypoxic-ischemic encephalopathy (HIE) is the most common brain injury in term neonates, often resulting in a global lack of oxygen (hypoxia) and blood flow (ischemia) to the developing brain. Neonates with HIE are at risk for cerebral palsy, epilepsy, vision impairment, and speech impairment, among other consequences. Currently, whole body cooling is used to reduce brain injury in neonates with HIE but additional therapeutic approaches will be critical to fully reduce the burden of injury and improve long-term outcomes.
The Russ lab employs a mouse model of perinatal HIE. Single-nucleus RNA sequencing from the cortex of mice after HIE reveals a number of changes in gene expression across different cortical cell types after injury when compared to control mice that only underwent a sham surgery. In particular, the Russ lab has identified an anti-inflammatory signaling molecule that is chronically suppressed after HIE. Readministering this anti-inflammatory molecule after HIE appears to reduce brain inflammation and the volume of brain injury compared to mice that only receive a placebo injection after injury. We hope that further study of this anti-inflammatory molecule will lead to its use in our aresenal to reduce the devastating consequences of HIE in babies.
Genetic Neurodevelopmental Disorders
Brain malformations and congenital disorders are often first diagnosed on ultrasound or MRI during fetal development or in the early postnatal period. Although these techniques are helpful for describing altered brain anatomy at a "zoomed out" structural level, we still have little understanding of exactly how distinct neuronal cell types and circuits are altered at a "zoomed in" level in these disorders. We are particularly interested in the cerebral cortex (the wrinkled outer surface of the brain), since the cortex plays a major role in cognitive, speech, and sensorimotor development.
To begin to understand how genetic disorders might selectively impact some cortical cell types over others, the Russ lab used a large-scale bioinformatic approach to examine biases in the expression of genes from single-gene neurodevelopmental disorders in single cell transcriptomic data from human cortex across development (Russ et al., Sci Rep, 2025). We demonstrated that genes associated with speech/cognitive delay and seizures were biased toward expression in excitatory cortical neurons and microglia and that these genes could be subdivided further based on whether or not they were associated with seizures. Together, this helps us build hypotheses about the types of cortical cells that may be more uniquely vulnerable to single-gene mutations in patients with neurodevelopmental disorders.
More recently, we have focused on a subpopulation of excitatory cortical neurons called intratelencephalic (IT) neurons that project only within telencephalic structures (i.e., the cortex and striatum). These neurons have been amplified and diversified throughout mammalian evoution and are therefore thought to uniquely contribute to human cognition. Their dysfunction has also been implicated in cognitive neurodevelopmental disorders, such as autism, and their axonal projections are disrupted in disorders of the corpus callosum (which is primarily made up of IT axons projecting to the contralateral hemisphere). However, despite their known diversity, IT neurons have classically been studied as a single large family, because, until recently, we lacked the tools to study them at a subtype level.
From his work in the Huang lab, Dr. Russ generated a battery of transgenic Cre- and Flp-mice that capitalize on marker genes expressed only in subsets of IT neurons, allowing us to label and manipulate IT subpopulations at unprecedented resolution. We aim to couple these mice with parallel studies in human induced pluripotent stem cell (iPSC)-derived cerebral organoids from patients with dysgenesis of the corpus callosum who are seen in Dr. Russ's clinic in order to learn more about how early neuron development and axon projections are disrupted in IT subpopulations in disorders of the corpus callosum.
Dr. Russ' Bio
Dr. Russ is a fetal/neonatal neurologist and developmental neuroscientist in the Departments of Pediatrics and Neurology at Duke. He completed his B.A. in Neuroscience at the University of Pennsylvania in 2008. He then pursued an MD-PhD through the Weill Cornell/Sloan Kettering/Rockefeller University MD-PhD Program where he graduated with joint degrees in 2016. Dr. Russ received his PhD in Neuroscience, studying under the mentorship of Dr. Julia Kaltschmidt where he studied how transcription factors control the identity of developing spinal interneurons, as well as how spinal inhibitory synapses respond to perinatal stroke. His research in early neurodevelopment led Dr. Russ to pursue clinical training in Child Neurology at the University of California San Francisco (UCSF), where he undertook additional elective training in neonatal neurology. Following residency, Dr. Russ was awarded the Child Neurologist Career Development Program (CNCDP) K12 from the National Institute of Neurological Disorders and Stroke (NINDS), which supported his transition to a junior faculty position at Duke and mentored research in the lab of Dr. Josh Huang in the Duke Department of Neurobiology. In Dr. Huang's lab, Dr. Russ gained experience using cutting-edge neuroscientific tools to study the genetics and cell development that guide formation of the cerebral cortex. Now Dr. Russ aims to combine his clinical and scientific training to study the detailed molecular and cellular pathophysiology in the cortex in perinatal brain injury and genetic neurodevelopmental disorders.