The Cammarato Lab is located in the Division of Cardiology in the Department of Medicine at the Johns Hopkins University School of Medicine. We are interested in basic mechanisms of striated muscle biology. We employ an array of imaging techniques to study “structural physiology” of cardiac and skeletal muscle. Drosophila melanogaster, the fruit fly, expresses both forms of striated muscle and benefits greatly from powerful genetic tools. We investigate conserved myopathic (muscle disease) processes and perform hierarchical and integrative analysis of muscle function from the level of single molecules and macromolecular complexes through the level of the tissue itself. Anthony Ross Cammarato, MD, is an assistant professor of medicine in the Cardiology Department. He studies the identification and manipulation of age- and mutation-dependent modifiers of cardiac function, hierarchical modeling and imaging of contractile machinery, integrative analysis of striated muscle performance and myopathic processes.

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 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.

Our lab is interested in understanding the fundamental mechanisms of how cells move and implications in disease treatment. We use an interdisciplinary approach involving fluorescent live cell imaging, genetics, and computer modeling to study the systems level properties of the biochemical networks that drive cell migration.

The Hillel Laboratory at Johns Hopkins investigates inflammatory, genetic, and molecular factors involved with laryngotracheal stenosis, or scar formation in the airway. Specifically, we are examining the interrelationship between genetics, the immune system, bacteria, and scar formation in the airway. The lab has developed unique models to study laryngotracheal stenosis and test drugs that may halt the progression of scar or reverse scar formation. We are also developing a drug-eluting stent to treat patients with laryngotracheal stenosis.

The O'Connor Lab studies the molecular basis of infectious disease using Legionella pneumophila pathogenesis as a model system. We are looking at the network of molecular interactions acting at the host-pathogen interface. Specifically, we use L. pneumophila pathogenesis to examine the numerous mechanisms by which an intracellular bacterial pathogen can establish infection, how it exploits host cell machinery to accomplish this, and how individual proteins and their component pathways coordinately contribute to disease. We are also studying the role of environmental hosts in the evolution of human pathogens. Using genetics and functional genomics, we compare and contrast the repertoires of virulence proteins required for growth in a broad assortment of hosts, how the network of molecular interactions differs between hosts, and the mechanisms by which L. pneumophila copes with this variation.

Research in the Rasika Mathias Lab focuses on the genetics of asthma in people of African ancestry. Our work led to the first genomewide association study of its kind in 2009. Currently, we are analyzing the whole-genome sequence of more than 1,000 people of African ancestry from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA). CAAPA’s goal is to use whole-genome sequencing to expand our understanding of how genetic variants affect asthma risk in populations of African ancestry and to provide a public catalog of genetic variation for the scientific community. We’re also involved in the study of coronary artery disease though the GeneSTAR Program, which aims to identify mechanisms of atherogenic vascular diseases and attendant comorbidities.

Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, we study the simian immunodeficiency virus (SIV) to determine the molecular basis for the development of HIV CNS, pulmonary and cardiac disease. Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. We are also interested in studies of lentivirus replication in macrophages and astrocytes and their role in the development of disease. These studies have led us to identify the viral genes that are important in neurovirulence of SIV and the development of CNS disease including NEF and the TM portion of ENV. The mechanisms of the action of these proteins in the CNS are complex and are under investigation. We have also developed a rapid, consistent SIV/macaque model in which we can test the ability of various antiviral and neuroprotective agents to reduce the severity of CNS and pulmonary disease.

The Shanthini Sockanathan Laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating neuronal and glial differentiation in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve these questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior.

The Joseph Mankowski Lab studies the immunopathogenesis of HIV infection using the SIV/macaque model. Our researchers use a multidisciplinary approach to dissect the mechanism underlying HIV-induced nervous system and cardiac diseases. Additionally, we study the role that host genetics play in HIV-associated cognitive disorders.