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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
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
The C. Kwon Lab studies the cellular and molecular mechanisms governing heart generation and regeneration.
The limited regenerative capacity of the heart is a major factor in morbidity and mortality rates: Heart malformation is the most frequent form of human birth defects, and cardiovascular disease is the leading cause of death worldwide. Cardiovascular progenitor cells hold tremendous therapeutic potential due to their unique ability to expand and differentiate into various heart cell types.
Our laboratory seeks to understand the fundamental biology and regenerative potential of multi-potent cardiac progenitor cells – building blocks used to form the heart during fetal development — by deciphering the molecular and cellular mechanisms that control their induction, maintenance, and differentiation. We are also interested in elucidating the maturation event of heart muscle cells, an essential process to generate adult cardiomyocytes, which occurs after terminal differentiation ...of the progenitor cells. We believe this knowledge will contribute to our understanding of congenital and adult heart disease and be instrumental for stem cell-based heart regeneration.
We have developed several novel approaches to deconstruct the mechanisms, including the use of animal models and pluripotent stem cell systems. We expect this knowledge will help us better understand heart disease and will be instrumental for stem-cell-based disease modeling and interventions for of heart repair.
Dr. Chulan Kwon is an assistant professor of medicine at the Johns Hopkins University Heart and Vascular Institute. view more
The Devreotes Laboratory is engaged in genetic analysis of chemotaxis in eukaryotic cells. Our long-term goal is a complete description of the network controlling chemotactic behavior. We are analyzing combinations of deficiencies to understand interactions among network components and carrying out additional genetic screens to identify new pathways involved in chemotaxis. A comprehensive understanding of this fascinating process should lead to control of pathological conditions such as inflammation and cancer metastasis.
The Espenshade Lab uses a multi-organismal and multidisciplinary approach to understand how eukaryotic cells measure insoluble lipids and dissolved gases. We have chosen cholesterol and oxygen as our model molecules, based on their essential roles in cell function and the importance of their proper homeostasis for human health.
The Fu Lab is a basic research lab that studies zinc transport, with a particular focus on which step in the zinc transport process may be modulated and how. Dr. Fu's lab uses parallel cell biology and proteomic approaches to understand how these physiochemical principles are applied to mammalian zinc transporters and integrated to the physiology of pancreatic beta cells. This research has implications for understanding how zinc transport is related to diabetes and insulin intake.
The Gabelli lab research is focused on structural, mechanistic and functional aspects of enzyme activation that play a role in the biology of human diseases such as cancer, parasitic infection and cardiovascular disease. Their work seeks to:
1. Understand how molecular events at the recognition level coordinate and trigger events in the cells
2. Translate structural and mechanistic information on protein:protein interactions at the cytoplasmic level into preventive and therapeutic treatment for human disease.
To achieve a comprehensive understanding, they are studying cytoplasmic protein-protein interactions involved in regulation of pathways such as PI3K and Sodium Voltage gated channels. Their research integrates structural biology and chemical biology and it is focused on drug discovery for targeted therapies.
The Goley Lab is broadly interested in understanding cellular organization and dynamic reorganization, with particular focus on the roles of the cytoskeleton in these phenomena. We use cell biological, biochemical, genetic and structural approaches to dissect cytoskeletal processes with the aim of understanding how they work in molecular detail. Currently, we are focused on investigating the mechanisms underlying cytokinesis in bacteria. A deep understanding of cytoskeletal function in bacteria will aid in the identification of targets for novel antibiotic therapies and in efforts in synthetic biology.
The Greider lab uses biochemistry to study telomerase and cellular and organismal consequences of telomere dysfunction. Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. The lab has generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations, when telomeres are short, cells die via apoptosis or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. The lab also is using the telomerase null mice to explore the essential role of telomerase stem cell viability. Telomerase mutations cause autosomal dominant dyskeratosis congenita. People with ...this disease die of bone marrow failure, likely due to stem cell loss. The lab has developed a mouse model to study this disease. Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated. view more
The Kazazian Lab focuses on the biology of LINE-1 (L1) retrotransposons. Retrotransposons are pieces of genomic DNA that have the ability to duplicate themselves and insert into a new genomic location. Current studies use innovative DNA sequencing to locate all human-specific L1s in any genome. By understanding L1 biology, we hope to better understand the role of these genomes and their behavior in complex human disease, such as cancer and mental disorders. The lab is also examining how to carry out gene therapy of hemophilia A using AAV vectors.