Ion channels are pore-forming membrane proteins gating the flow of ions across the cell membrane. Among their many functions, ion channels regulate cell volume, control epithelial fluid secretion, and generate the electrical impulses in our brain. The Qiu Lab employs a multi-disciplinary approach including high-throughput functional genomics, electrophysiology, biochemistry, and mouse genetics to discover novel ion channels and to elucidate their role in health and disease.

The O’Rourke Lab uses an integrated approach to study the biophysics and physiology of cardiac cells in normal and diseased states. Research in our lab has incorporated mitochondrial energetics, Ca2+ dynamics, and electrophysiology to provide tools for studying how defective function of one component of the cell can lead to catastrophic effects on whole cell and whole organ function. By understanding the links between Ca2+, electrical excitability and energy production, we hope to understand the cellular basis of cardiac arrhythmias, ischemia-reperfusion injury, and sudden death. We use state-of-the-art techniques, including single-channel and whole-cell patch clamp, microfluorimetry, conventional and two-photon fluorescence imaging, and molecular biology to study the structure and function of single proteins to the intact muscle. Experimental results are compared with simulations of computational models in order to understand the findings in the context of the system as a whole. Ongoing studies in our lab are focused on identifying the specific molecular targets modified by oxidative or ischemic stress and how they affect mitochondrial and whole heart function. The motivation for all of the work is to understand • how the molecular details of the heart cell work together to maintain function and • how the synchronization of the parts can go wrong Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms. Brian O’Rourke, PhD, is a professor in the Division of Cardiology and Vice Chair of Basic and Translational Research, Department of Medicine, at the Johns Hopkins University.

The Dong Laboratory has identified many genes specifically expressed in primary sensory neurons in dorsal root ganglia (DRG). Our lab uses multiple approaches, including molecular biology, mouse genetics, mouse behavior and electrophysiology, to study the function of these genes in pain and itch sensation. Other research in the lab examines the molecular mechanism of how skin mast cells sensitize sensory nerves under inflammatory states.

The mission and interest of the neuroengineering and Biomedical Instrumentation Lab is to develop novel instrumentation and technologies to study the brain at several levels--from single cell to the whole brain--with the goal of translating the work into practical research and clinical applications. Our personnel include diverse, independent-minded and entrepreneurial students, post docs, and research faculty who base their research on modern microfabrication, stem cell biology, electrophysiology, signal processing, image processing, and integrated circuit design technologies.

Research in the Bradley Undem Lab centers around the hypothesis that the peripheral nervous system is directly involved in the processes of inflammation. This hypothesis is being studied primarily in the central airways and sympathetic ganglia. We are addressing this in a multidisciplinary fashion, using pharmacological, electrophysiological, biochemical and anatomical methodologies.

The Brown Lab is focused on the function of the cerebral cortex in the brain, which underlies our ability to interact with our environment through sensory perception and voluntary movement. Our research takes a bottom-up approach to understanding how the circuits of this massively interconnected network of neurons are functionally organized, and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders, including autism and schizophrenia. By combining electrophysiological and optogenetic approaches with anatomical and genetic techniques for identifying cell populations and pathways, the Brown Lab is defining the synaptic interactions among different classes of cortical neurons and determining how long-range and local inputs are integrated within cortical circuits. In amyotrophic lateral sclerosis, corticospinal and spinal motor neurons progressively degenerate. The Brown Lab is examining how abnormal activity within cortical circuits contributes to the selective degeneration of corticospinal motor neurons in an effort to identify new mechanisms for treating this disease. Abnormalities in the organization of cortical circuits and synapses have been identified in genetic and anatomical studies of neuropsychiatric disease. We are interested in the impact these abnormalities have on cortical processing and their contribution to the disordered cognition typical of autism and schizophrenia.

Our mission is to reveal the molecular logic of our intelligence in health and disease. We use advanced molecular biological tools and state-of-the-art neuroscience to test the role of synaptic and neuronal molecules in the dynamics of the living brain.

Artificial neural networks have been heavily inspired by the brain’s architecture, guiding our journey to discovering the keys to intelligence. We now find ourselves at a pivotal moment: today's AI systems surpass biological circuits in certain tasks, yet we still lack a fundamental understanding of the mechanisms behind the brain’s superior cognitive flexibility and efficiency. At Ingie Hong’s Quantitative Intelligence Lab, we are dedicated to unraveling the principles that enable the mammalian cortex to achieve remarkable feats of intelligence, including rapid learning, generalization, and inference across vast stores of memory.

A single neuron’s response depends on its synaptic connections and intrinsic properties, which are dictated by the expression of neuronal genes. However, the role of these molecules in brain computations remains largely uncharted territory. Focusing on the mouse visual cortex as a starting point for broader generalization, and using large-scale electrophysiology, advanced microscopy, and machine learning, we have begun to uncover the impact of key synaptic genes on cortical processing and their role in the brain’s “working algorithm” (Hong et al., Nature, 2024). Our molecular tools, including gene therapy vectors and antisense oligonucleotides, show promise as effective therapeutic candidates.

Our research will advance the nascent field of 'neurocomputational therapeutics'—innovative genetic and pharmacological tools that address biases in neural activity. These tools will not only facilitate the development of novel mechanism-based treatments for brain disorders but also inspire the next generation of intelligent artificial neural networks.

The Caterina lab is focused on dissecting mechanisms underlying acute and chronic pain sensation. We use a wide range of approaches, including mouse genetics, imaging, electrophysiology, behavior, cell culture, biochemistry and neuroanatomy to tease apart the molecular and cellular contributors to pathological pain sensation. A few of the current projects in the lab focus on defining the roles of specific subpopulations of neuronal and non-neuronal cells to pain sensation, defining the role of RNA binding proteins in the development and maintenance of neuropathic pain, and understanding how rare skin diseases known as palmoplantar keratodermas lead to severe pain in the hands and feet.

Epilepsy affects 1-3% of the population and can have a profound impact on general health, employment and quality of life. Medial temporal lobe epilepsy (MTLE) develops in some patients following head injury or repeated febrile seizures. Those affected may first suffer spontaneous seizures many years after the initial insult, indicating that the neural circuit undergoes a slow pathologic remodeling over the interim. There are currently no methods of preventing the development of MTLE. It is our goal to better understand the process in order to slow, halt, and ultimately reverse it. Our laboratory draws on electrophysiology, molecular biology, and morphology to study the contribution of dysregulated neurogenesis and newborn neuron connectivity to the development of MTLE. We build on basic research in stem cell biology, hippocampal development, and synaptic plasticity. We work closely with colleagues in the Institute for Cell Engineering, Neurology, Neurosurgery, Biomedical Engineering, and Radiology. As physician neuropathologists our grounding is in tissue alterations underlying human neurologic disease; using human iPSC-derived neurons and surgical specimens we focus on the pathophysiological processes as they occur in patients. By understanding changes in cell populations and morphologies that affect the circuit, and identifying pathologic alterations in gene expression that lead to the cell-level abnormalities, we hope to find treatment targets that can prevent the remodeling and break the feedback loop of abnormal activity > circuit change > abnormal activity.

The Arking Lab studies the genomics of complex human disease, with the primary goal of identifying and characterizing genetics variants that modify risk for human disease. The group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. The lab is currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify specific genetic influences of disease. The Arking Lab is actively involved in researching: • autism, a childhood neuropsychiatric disorder • cardiovascular genomics, with a focus on electrophysiology and sudden cardiac death (SCD) • electrophysiology is the study of the flow of ions in biological tissues Dan E. Arking, PhD, is an associate professor at the McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Division of Cardiology, Johns Hopkins University.