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.

Research in the Joseph Margolick Lab focuses on the many effects of HIV/AIDS on human health. We are particularly interested in the mechanisms of T-cell loss and preservation among people infected with HIV and the evaluation of human immune functions.

Research in the James Knierim Laboratory attempts to understand the flow of information through the hippocampal formation and the computations performed by the various subfields of the hippocampus and its inputs from the entorhinal cortex. To address these issues, we use multi-electrode arrays to record the extracellular action potentials from scores of well-isolated hippocampal neurons in freely moving rats. These neurons, or ""place cells,"" are selectively active when the rat occupies restricted locations in its environment and help to form a cognitive map of the environment. The animal uses this map to navigate efficiently in its environment and to learn and remember important locations. These cells are thought to play a major role in the formation of episodic (autobiographical) memories. Place cells thus constitute a tremendous opportunity to investigate the mechanisms by which the brain transforms sensory input into an internal, cognitive representation of the world and then uses this representation as the framework that organizes and stores memories of past events.

The clinical development of novel immune and stem cell therapies calls for suitable methods that can follow the fate of cells non-invasively in humans at high resolution. The Bulte Lab has pioneered methods to label cells magnetically (using tiny superparamagnetic iron oxide nanoparticles) in order to make them visible by MR imaging. While the lab is doing basic bench-type research, there is a strong interaction with the clinical interventional radiology and oncology groups in order to bring the methodologies into the clinic.

Research in the Jeremy Sugarman Lab focuses on biomedical ethics—particularly, the application of empirical methods and evidence-based standards to the evaluation and analysis of bioethical issues. Our contributions to medical ethics and health policy include work on the ethics of informed consent, umbilical cord blood banking, stem cell research, international HIV prevention research, global health and research oversight.

The Jun O. Liu Laboratory tests small molecules to see if they react in our bodies to find potential drugs to treat disease. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases. Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation.

The research program aims to advance cardiovascular biology and medicine by focusing on pluripotent stem cell-based modeling and therapy and by nurturing future leaders in regenerative medicine.

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.

The Johns Hopkins Center for Epithelial Disorders focuses on research into the physiology and pathophysiology of epithelial cells (cells that line the cavities and interior surfaces of the body) of the gastrointestinal (GI) tract, liver, pancreas and kidney. Specifically, the center’s research seeks to: -Understand the mechanisms regulating the activity of transport proteins (including channels) of epithelial cells Characterize the mechanisms by which polarity of epithelial cells are maintained -Investigate the mechanisms controlling transcription of epithelial-specific genes Understand the pathophysiological basis of GI and renal diseases that involve the preceding three components -The center also provides a framework for training fellows in gastroenterology and hepatology to become independent investigators. The center is funded primarily through individual investigator-initiated extramural research grant support from the National Institutes of Health (NIH) as well as multi-investigator grants including RO1, PO1, UO1 and R24.

Dr. Colantuoni and his colleagues explore human brain development and molecular mechanisms that give rise to risk for complex brain disease. His team uses genomic technologies to examine human brain tissue as well as stem models and vast public data resources.