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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.
Alain Labrique Lab
The Alain Labrique Lab conducts research on infectious diseases and public health. Our team studies the various factors that lead to maternal and neonatal mortality, particularly in underserved populations in South Asia, using the tools of infectious disease epidemiology, molecular biology and biostatistics. We work to better understand factors such as the interface of micronutrient deficiency and maternal/infant mortality and the prevention of nosocomial infections through mechanistic or nutritional interventions. We also have a longstanding interest in technologies that may enable early detection of disease.
The Lau Lab uses a combination of computational and experimental approaches to study the atomic and molecular details governing the function of protein complexes involved in intercellular communication. We study ionotropic glutamate receptors (iGluRs), which are ligand-gated ion channels that mediate the majority of excitatory synaptic transmission in the central nervous system. iGluRs are important in synaptic plasticity, which underlies learning and memory. Receptor dysfunction has been implicated in a number of neurological disorders.
Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.
Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets a...ppear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.
Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
• Ion channel biology and arrhythmias
• Cardiac pacemaker physiology and disease
• Molecular physiology of CaMKII
• Myocardial and mitochondrial metabolism
• CaMKII and reactive oxygen species in asthma
Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital. view less
Researchers in the Center for Cell Dynamics study spatially and temporally regulated molecular events in living cells, tissues and organisms. The team develops and applies innovative biosensors and imaging techniques to monitor dozens of critical signaling pathways in real time. The new tools help them investigate the fundamental cellular behaviors that underlie embryonic development, wound healing, cancer progression, and functions of the immune and nervous systems.
Andrew Lane Lab
The Lane laboratory is focused on understanding molecular mechanisms underlying chronic rhinosinusitis and particularly the pathogenesis of nasal polyps. Diverse techniques in molecular biology, immunology, physiology, and engineering are utilized to study epithelial cell innate immunity, olfactory loss, the sinus microbiome, and drug delivery to the nose and sinus cavities. Ongoing work explores how epithelial cells participate in the immune response and contribute to chronic sinonasal inflammation. The lab creates and employs transgenic mouse models of chronic sinusitis to support research in this area. Collaborations are in place with the School of Public Health to explore mechanisms of anti-viral immunity in influenza and rhinovirus, and with the University of Maryland to characterize the bacterial microbiome of the nose and sinuses in health and disease.
Andrew McCallion Laboratory
The McCallion Laboratory studies the roles played by cis-regulatory elements (REs) in controlling the timing, location and levels of gene activation (transcription). Their immediate goal is to identify transcription factor binding sites (TFBS) combinations that can predict REs with cell-specific biological control--a first step in developing true regulatory lexicons.
As a functional genetic laboratory, we develop and implement assays to rapidly determine the biological relevance of sequence elements within the human genome and the pathological relevance of variation therein. In recent years, we have developed a highly efficient reporter transgene system in zebrafish that can accurately evaluate the regulatory control of mammalian sequences, enabling characterization of reporter expression during development at a fraction of the cost of similar analyses in mice. We employ a range of strategies in model systems (zebrafish and mice), as well as analyses in the human population, to illu...minate the genetic basis of disease processes. Our long-term objective is to use these approaches in contributing to improved diagnostic, prognostic and therapeutic strategies in patient care. view more
Molecular and Comparative Pathobiology
The main focus of the Becker lab has been on the mechanisms and consequences of post-ischemic myocardial inflammation.
Genomic control of platelet function:
Aggregation of blood platelets initiates clotting in coronary arteries, the main cause of heart attacks. Our laboratory conducts experiments to understand how genes control platelet function. Through funding by the National Heart Lung and Blood Institute, we have performed candidate gene analysis, linkage studies, whole genome association studies, and now whole genome sequencing in about 2000 healthy subjects from families with early onset coronary artery disease. The subjects are siblings or offspring of an individual identified with coronary artery disease before age 60 in the GeneSTAR Research Program (Genetic Studies of Atherosclerosis Risk). We have identified a large number of common and rare genetic variants associated with platelet aggregation, and although some variants are located in genes known to be important in... the biology of platelet function, most are in non-protein coding regions of genes (introns) or in intergenic regions of the genome. To understand better how these variants influence platelet function, we created pluripotent stem cells from blood mononuclear cells in 257 genotyped GeneSTAR subjects and then transformed the stem cells to megakaryocytes, the source of platelets in the bone marrow. We have determined the entire transcriptome of these megakaryocytes to measure gene expression levels in an effort to functionally link genetic variation with platelet function. We are also interested in epigenetic effects which regulate the amount of gene transcription and resulting protein formation. We have done similar transcriptomic and proteomic studies in blood platelets as we have in stem cell-derived megakaryocytes.
Our goal is to identify new therapeutic targets for drug development to control excessive platelet aggregation and reduce the risk of heart attack in susceptible individuals. We also hope to use the genetic information to predict who is at greatest risk for platelet aggregation or bleeding, and tailor treatment to effectively apply individualized precision medicine.
The Becker laboratory also extends its cardiovascular work well beyond platelet function, as noted on the GeneSTAR Research Program website. view less
The goal of research in the Beer Lab is to understand how gene regulatory information is encoded in genomic DNA sequence. Our work uses functional genomics DNase-seq, ChIP-seq, RNA-seq, and chromatin state data to computationally identify combinations of transcription factor binding sites that operate to define the activity of cell-type specific enhancers. We are currently focused on improving SVM methodology by including more general sequence features and constraints predicting the impact of SNPs on enhancer activity (delta-SVM) and GWAS association for specific diseases, experimentally assessing the predicted impact of regulatory element mutation in mammalian cells, systematically determining regulatory element logic from ENCODE human and mouse data, and using this sequence based regulatory code to assess common modes of regulatory element evolution and variation.
Mitochondrial dysfunction has long been a consistent observation in Parkinson's disease. To understand the consequences of Parkinson's disease causing genetic mutations on the function of mitochondria, the Bioenergetics Core B will provide the following analyses to the projects in the Udall Center at Johns Hopkins: (1) Measuring rates of respiration, oxygen consumption and ATP generation, (2) Measuring calcium dynamics, (3) Measuring reactive oxygen and reactive nitrogen species, (4) Measuring the activity of the electron transport chain enzymes and metabolic enzymes, and (5) Measuring plasma versus mitochondrial membrane potential and mitochondrial membrane permeability