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 Chloe Thio lab focuses on several areas. First, HBV virology and immunology in HBV monoinfected and HIV-HBV co-infected individuals that will ultimately help develop a cure for HBV. Second, HCV infection in men who have sex with men. Third, non-alcoholic fatty liver disease with a focus on HIV-infected individuals. Fourth, host genetic determinants of spontaneous HBV recovery and HCV clearance.

Research in the Casey Overby Lab focuses on the intersection of public health genomics and biomedical informatics. We’re currently developing applications to support the translation of genomic research to clinical and population-based health care settings. We’re also working to develop knowledge-based ways to use big data — including electronic health records — to improve population health.

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.

Work in the Enid Neptune Lab focuses on topics within the fields of pulmonary and critical care medicine. Our research centers primarily on therapeutic strategies for Marfan syndrome and hepatocyte growth factor signaling in airspace homeostasis. We also conduct research on chronic obstructive pulmonary disease (COPD), with a focus on its mechanisms and potential methods for preventing its progression. Our research within critical care has most recently involved investigating superoxide dismutase 3 dysregulation in neonatal lung injuries.

The Elizabeth Selvin Lab examines the intersection of epidemiology, clinical policy and public health policy. One of our key goals is to use the findings of epidemiologic research to inform the screening, diagnosis and treatment of diabetes, cardiovascular disease and kidney disease. Much of our work looks at biomarkers and diagnostics related to diabetes and diabetes complications. Our findings — linking hemoglobin A1c (HbA1c) to diabetic complications and identifying the role of A1c in diabetes diagnosis — have influenced clinical practice guidelines.

Dr. Kraus’ team investigates the factors that impact the long-term success or failure of kidney transplants as well as barriers to nephrology care and transplants in minority populations. We research many topics dealing with kidney transplant rejection, including diagnostic criteria, infection risk and incompatibility factors. Our lab also has a longstanding interest in pancreas transplants and has conducted research to establish guidelines for diagnosing antibody-mediated rejection of pancreas allografts-updated Banff grading schema.

Research efforts in the Edward Chen Lab focus on bleomycin-induced pulmonary fibrosis and granulomatous inflammation as well as clinical and translational studies in sarcoidosis. Our studies have included topics such as the etiologies of sarcoidosis, hylleraas hydride binding energy in diatomic electron affinities, and molecular convergence of neurodevelopmental disorders. We have also investigated the use of quantitative mass spectrometric analysis to better understand the mechanisms of phospho-priming and auto-activation of the checkpoint kinase Rad53 in vivo.

The Erika Matunis Laboratory studies the stem cells that sustain spermatogenesis in the fruit fly Drosophila melanogaster to understand how signals from neighboring cells control stem cell renewal or differentiation. In the fruit fly testes, germ line stem cells attach to a cluster of non-dividing somatic cells called the hub. When a germ line stem cell divides, its daughter is pushed away from the hub and differentiates into a gonialblast. The germ line stem cells receive a signal from the hub that allows it to remain a stem cell, while the daughter displaced away from the hub loses the signal and differentiates. We have found key regulatory signals involved in this process. We use genetic and genomic approaches to identify more genes that define the germ line stem cells' fate. We are also investigating how spermatogonia reverse differentiation to become germ line stem cells again.

Utilizing a combination of tissue-based, cell-based, and molecular approaches, our research goals focus on abnormal telomere biology as it relates to cancer initiation and tumor progression, with a particular interest in the Alternative Lengthening of Telomeres (ALT) phenotype. In addition, our laboratories focus on cancer biomarker discovery and validation with the ultimate aim to utilize these novel tissue-based biomarkers to improve individualized prevention, detection, and treatment strategies.