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George Rose Lab
The George Rose Lab investigates protein folding, the spontaneous disorder transition that takes place under physiological conditions. The protein polymer is flexible in its unfolded state but takes on a unique native, three-dimensional form when folded. We propose that the folded state is selected from a set number of structural possibilities, each corresponding to either a distinct hydrogen-bonded arrangement of ??helices or a strand of ??sheet.
Herschel Wade Lab
The emergence of structural genomics, proteomics and the large-scale sequencing of many genomes provides experimental access to regions of protein sequence-structure-function landscapes which have not been explored through traditional biochemical methods. Protein structure-function relationships can now be examined rigorously through the characterization of protein ensembles, which display structurally convergent--divergent solutions to analogous or very similar functional properties.
In this modern biochemical context, the Herschel Wade Lab will use protein libraries, chemistry, biophysics, molecular biology and structural methods to examine the basis of molecular recognition in the context of several important biological problems, including structural and mechanistic aspects of multi-drug resistance, ligand-dependent molecular switches and metal ion homeostasis.
The research in the Kecken Zhang Laboratory is focused on theoretical and computational neuroscience. We use mathematical analysis and computer simulations to study the nervous system at multiple levels, from realistic biophysical models to simplified neuronal networks. Several of our current research projects involve close collaborations with experimental neuroscience laboratories.
The Michael Caterina Lab studies the biological functions and biophysical characteristics of a group of ion channel proteins of the transient receptor potential vanilloid (TRPV) family--TRPV1, TRPV2, TRPV3 and TRPV4.
These channels can be activated by warm or painfully hot temperatures, as well as by many nonthermal stimuli. Our lab is dissecting the biological contributions of these channels to thermosensory and nonthermosensory processes in both neuronal and nonneuronal cells. The goal of their research is to more broadly understand the biological and pathophysiological basis of chronic pain.
Michael Edidin Lab
The Michael Edidin Lab studies membrane dynamics and organization in cells from lymphocytes to epithelial cells using biochemistry, biophysics (especially fluorescence methods), cell biology, biochemistry and immunology. We are interested in transplantation immunology, particularly in the cell biology of class I MHC molecules, and are working to understand the relationship between plasma membrane biophysics and antigen presentation by MHC molecules. We are currently studying the clustering of T cell receptors for the antigen TCR.
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. view more
Ryuya Fukunaga Lab
The Fukunaga Lab uses multidisciplinary approaches to understand the cell biology, biogenesis and function of small silencing RNAs from the atomic to the organismal level.
The lab studies how small silencing RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), are produced and how they function. Mutations in the small RNA genes or in the genes involved in the RNA pathways cause many diseases, including cancers. We use a combination of biochemistry, biophysics, fly genetics, cell culture, X-ray crystallography and next-generation sequencing to answer fundamental biological questions and also potentially lead to therapeutic applications to human diseases.
The Stivers Lab is broadly interested in the biology of the RNA base uracil when it is present in DNA. Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. We use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and HIV-1 pathogenesis.
The research in the Svetlana Lutsenko Laboratory is focused on the molecular mechanisms that regulate copper concentration in normal and diseased human cells. Copper is essential for human cell homeostasis. It is required for embryonic development and neuronal function, and the disruption of copper transport in human cells results in severe multisystem disorders, such as Menkes disease and Wilson's disease. To understand the molecular mechanisms of copper homeostasis in normal and diseased human cells, we utilize a multidisciplinary approach involving biochemical and biophysical studies of molecules involved in copper transport, cell biological studies of copper signaling, and analysis of copper-induced pathologies using Wilson's disease gene knock-out mice.
The Tom Woolf Lab studies the quarter of the genome devoted to membrane proteins. This rapidly growing branch of bioinformatics, which includes computational biophysics, represents the main research direction of our group. We aim to provide insight into critical issues for membrane systems. In pursuit of these goals, we use extensive computer calculations to build an understanding of the relations between microscopic motions and the world of experimental measurements. Our calculations use our own Beowulf computer cluster as well as national supercomputer centers. An especially strong focus has been on the computed motions of proteins and all-atom models of the lipid bilayers that mediate their influence. To compute these motions, we use the molecular dynamics program CHARMM. We hope to use our understanding of the molecular motions for the prediction of membrane protein structures using new computational methods.