The long-term objectives of our research team are: a. to understand the molecular etiology in the development of human cancer, and b. to identify and characterize cancer molecules for cancer detection, diagnosis, and therapy. We use ovarian carcinoma as a disease model because it is one of the most aggressive neoplastic diseases in women. For the first research direction, we aim to identify and characterize the molecular alterations during initiation and progression of ovarian carcinomas.

Research conducted in the Gary Wand Lab focuses on neuropsychoendocrinology; the neurobiology of substance abuse; physiogenetics and regulation of the stress response; and the relationship between stress and chemical dependency. Current studies seek to better understand the genetic determinants of the stress response and how excessive stress hormone production contributes to neurobiological disorders, including addiction.

Research in the Gail Daumit Lab is devoted to improving overall health and decreasing premature mortality for people with serious mental illnesses, such as schizophrenia and bipolar disorder. We have conducted observational studies to determine and convey the burden of physical health problems in this vulnerable population, and are currently leading a randomized trial funded by the National Heart, Lung, and Blood Institute to test a comprehensive cardiovascular risk reduction program in people with serious mental illness.

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.

Johns Hopkins is a member of the Specialized Program of Research Excellence (SPORE) in Cervical Cancer. With a $11.5 million grant from the National Cancer Institute, we are conducting lab, translational and clinical studies to prevent and treat cervical cancers. Previous studies have identified connections between immune system genes and HPV16. Current projects include the development of next-generation HPV vaccines to control HPV-associated precursor lesions and invasive cancer. Our dedicated researchers are working to extend the techniques used in HPV vaccine development to the creation of vaccines targeting other cancers with defined tumor antigens.

The Bradford Winters Lab conducts research on patient safety and quality of care. Our team focuses on the topics of patient care in the intensive care unit, evidence-based medicine, quality health care, and the measurement and evaluation of safety efforts. Currently our work involves evaluating pain management techniques in post-craniotomy patients, developing guidelines for policy development of patient safety initiatives and creating measures for rapid-response system outcomes.

The Berger Lab's research is focused on understanding how multi-subunit assemblies use ATP for overcoming topological challenges within the chromosome and controlling the flow of genetic information. A long-term goal is to develop mechanistic models that explain in atomic level detail how macromolecular machines transduce chemical energy into force and motion, and to determine how cells exploit and control these complexes and their activities for initiating DNA replication, shaping chromosome superstructure and executing myriad other essential nucleic-acid transactions. Our principal approaches include a blend of structural (X-ray crystallography, single-particle EM, SAXS) and solution biochemical methods to define the architecture, function, evolution and regulation of biological complexes. We also have extensive interests in mechanistic enzymology and the study of small-molecule inhibitors of therapeutic potential, the development of chemical approaches to trapping weak protein/protein and protein/nucleic acid interactions, and in using microfluidics and single-molecule approaches for biochemical investigations of protein dynamics.

Research in the Bakker Memory Laboratory is focused on understanding the mechanisms and brain networks underlying human cognition with a specific focus on the mechanisms underlying learning and memory and the changes in memory that occur with aging and disease. We use a variety of techniques including neuropsychological assessments, experimental behavioral assessments and particularly advanced neuroimaging methods to study these questions in young and older adults and patients with mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease and epilepsy. Through our collaborations with investigators in both basic science and clinical departments, including the departments of Psychiatry and Behavioral Sciences, Psychological and Brain Sciences, Neurology and Public Health, our research also focuses on brain systems involved in spatial navigation and decision-making as well as cognitive impairment in neuropsychiatric conditions such as schizophrenia, eating disorders, obsessive-compulsive disorders, depression and anxiety.

The Brown Lab is focused on the function of the cerebral cortex in the brain, which underlies our ability to interact with our environment through sensory perception and voluntary movement. Our research takes a bottom-up approach to understanding how the circuits of this massively interconnected network of neurons are functionally organized, and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders, including autism and schizophrenia. By combining electrophysiological and optogenetic approaches with anatomical and genetic techniques for identifying cell populations and pathways, the Brown Lab is defining the synaptic interactions among different classes of cortical neurons and determining how long-range and local inputs are integrated within cortical circuits. In amyotrophic lateral sclerosis, corticospinal and spinal motor neurons progressively degenerate. The Brown Lab is examining how abnormal activity within cortical circuits contributes to the selective degeneration of corticospinal motor neurons in an effort to identify new mechanisms for treating this disease. Abnormalities in the organization of cortical circuits and synapses have been identified in genetic and anatomical studies of neuropsychiatric disease. We are interested in the impact these abnormalities have on cortical processing and their contribution to the disordered cognition typical of autism and schizophrenia.

The Best Laboratory focus on therapeutic vaccine development for HPV-related diseases by developing a murine model of papilloma analogous to Recurrent Respiratory Papillomatosis (RRP) for testing of DNA vaccine technology. We also work to understand the immunosuppressive tumor microenvironment that facilitates RRP development, and translate this work into novel therapies and clinical practice.