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The Advanced Optics Lab uses innovative optical tools, including laser-based nanotechnologies, to understand cell motility and the regulation of cell shape. We pioneered laser-based nanotechnologies, including optical tweezers, nanotracking, and laser-tracking microrheology. Applications range from physics, pharmaceutical delivery by phagocytosis (cell and tissue engineering), bacterial pathogens important in human disease and cell division.
Other projects in the lab are related to microscopy, specifically combining fluorescence and electron microscopy to view images of the subcellular structure around proteins.
Research in the Alex Kolodkin Laboratory is focused on understanding how neuronal connectivity is established during development. Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology and synapse formation and function. We have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors. We employ a cross-phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology and synaptogenesis. We also seek to understand how these signals are transduced to cytosolic effectors. Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function. Our current work includes a relatively new interest in ...understanding the origins of laminar organization in the central nervous system. view more
Anne Murphy Laboratory
Anne Murphy’s laboratory studies cardiomyopathy and key proteins that are part of the contractile apparatus. The team is looking at how modifications to these proteins might affect various diseases and heart failure. She also investigates the role of genetics in pediatric heart failure associated with acute heart failure, which is sometimes attributed to myocarditis. Her laboratory has received grants from the American Heart Association, the National Institutes of Health and the Children’s Cardiomyopathy Foundation. Murphy received the Rowe Award for Cardiology Research from the Society for Pediatric Research and other awards. Her research on the molecular basis of myocardial stunning was named one of the top 10 research achievements for 1999 by the American Heart Association.
The Machamer Lab is interested in the structure and function of the Golgi complex, an ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids in the secretory pathway. One goal of our research is to understand the role of this structure in Golgi function by targeting and function of resident Golgi proteins. The other research interest in the lab is the assembly mechanism of coronaviruses, enveloped viruses that bud into Golgi compartments. We are addressing how coronaviruses target their envelope proteins to Golgi membranes, and how they interact with each other at the virus assembly site. We are also exploring how coronaviruses are exocytosed after they bud into the Golgi lumen. Our long-term goal is to understand the advantages of intracellular assembly for coronaviruses.
The CRCIF was established to foster collaborative efforts aimed at elucidating the role of intermediate filaments (IFs) in the heart. Intermediate filaments constitute a class of cytoskeletal proteins in metazoan cells, however, different from actin microfilaments and tubulin microtubules, their function in cardiac cells is poorly understood. Unique from the other two components of the cytoskeleton, IFs are formed by cell type-specific proteins. Desmin is the main component of the IFs in the cardiac myocytes. We measured the consistent induction of desmin post-translational modifications (PTMs, such as phosphorylation, etc.) in various clinical and experimental models of heart failure. Therefore, one of our main focuses is to determine the contribution of desmin PTMs to the development of heart failure in different animal and clinical models.
• Quantification of desmin PTM-forms in different forms of heart failure at the peptide level using mass spectrometry
• F...unctional assessment of the role of desmin PTMs in heart failure development using single site mutagenesis and biophysical methods
• Molecular characterization of desmin preamyloid oligomers using mass spectrometry, in vitro and in vivo imaging
• Assessment of the diagnostic and pharmacological value of desmin PTMs in heart failure development view more
David Graham Lab
The David Graham Lab studies the consequences of HIV interactions with the immune system, the resulting pathogenesis and how to sabotage these interactions. We apply advanced technologies like mass spectrometry to dissect processes at the molecular level. We are also actively involved in cardiovascular research and studies the ways proteins are organized into functional units in different cell types of the heart.
Major projects in our lab are organized into three major areas: (1) H/SIV pathogenesis and neuropathogenesis, (2) Cardiovascular disease, and (3) High technology development
Molecular and Comparative Pathobiology
Research in the Dolores Njoku Lab focuses on immune-mediated liver injury caused by drugs such as anti-seizure medications and antibiotics. We use an animal model to understand the pathways involved in the injury process, recognizing that this model can also uncover pathways involved with other drugs that cause similar liver injury. We hope to uncover the immunogenic epitopes, or pieces, of the proteins that trigger the autoimmune reaction and identify the key regulatory pathways involved.
Current projects include:
The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors.
This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.
The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen... based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed .
This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.
The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics. view less
The Erika Darrah Lab is primarily interested in the mechanisms underlying the development and progression of autoimmunity in rheumatoid arthritis (RA), with a particular focus on the peptidyl arginine deiminase (PAD) enzymes. We’re focused on understanding the development of PAD4-activating autoantibodies over time and how they contribute to the development of erosive disease. Studies are underway to determine if the newly discovered antibody is mimicking a naturally occurring PAD4 binding partner and to identify potentially pro-inflammatory effects of citrullinated proteins on effector cells of the immune system.
The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental problems in the fields of cardiac preconditioning and heart failure. Protein networks are perturbed in heart disease in a manner that correlates only weakly with changes in mRNA transcripts. Moreover, proteomic techniques afford the systematic assessment of post-translational modifications that regulate the activity of proteins responsible for every aspect of heart function from electrical excitation to contraction and metabolism. Understanding the status of protein networks in the diseased state is, therefore, key to discovering new therapies.
D. Brian Foster, Ph.D., is an assistant professor of medicine in the division of cardiology, and serves as Director of the Laboratory of Cardiovascular Biochemistry at the Johns Hopkins University School of Medicine.