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.

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.

The Bert Vogelstein Laboratory seeks to develop new approaches to the prevention or treatment of cancers through a better understanding of the genes and pathways underlying their pathogenesis. Our major focus is on cancers of the colon and rectum. We have shown that each colon neoplasm arises from a clonal expansion of one transformed cell. This expansion gives rise to a small benign colon tumor (called a polyp or adenoma). This clonal expansion and subsequent growth of the tumors appears to be caused by mutations in oncogenes and tumor suppressor genes, and the whole process is accelerated by defects in genes required for maintaining genetic instability. Mutations in four or five such genes are required for a malignant tumor to form, while fewer mutations suffice for benign tumorigenesis. As the mutations accumulate, the tumors become progressively more dangerous. Current studies are aimed at the further characterization of the mechanisms through which these genes act, the identification of other genes that play a role in this tumor type, and the application of this knowledge to patient management.

Dr. Bhujwalla’s lab promotes preclinical and clinical multimodal imaging applications to understand and effectively treat cancer. The lab’s work is dedicated to the applications of molecular imaging to understand cancer and the tumor environment. Significant research contributions include 1) developing ‘theranostic agents’ for image-guided targeting of cancer, including effective delivery of siRNA in combination with a prodrug enzyme 2) understanding the role of inflammation and cyclooxygenase-2 (COX-2) in cancer using molecular and functional imaging 3) developing noninvasive imaging techniques to detect COX-2 expressing in tumors 4) understanding the role of hypoxia and choline pathways to reduce the stem-like breast cancer cell burden in tumors 5) using molecular and functional imaging to understand the role of the tumor microenvironment including the extracellular matrix, hypoxia, vascularization, and choline phospholipid metabolism in prostate and breast cancer invasion and metastasis, with the ultimate goal of preventing cancer metastasis and 6) molecular and functional imaging characterization of cancer-induced cachexia to understand the cachexia-cascade and identify novel targets in the treatment of this condition.

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.