The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatocellular carcinoma and the development of molecular markers to help diagnose and manage cancer of the liver. In addition, we are investigating biomarkers for early diagnosis, prognosis and response to various treatment modalities. Results of this study will provide a molecular classification of HCC and allow us to identify targets for chemoprevention and treatment. Specifically, we extract genomic DNA and total RNA from liver tissues and use this genetic material for methylation-specific PCR (MSP), cDNA microarray, microRNA microarray and genomic DNA methylation array experiments.

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.

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.

Dr. Meltzer is an internationally renowned leader in the molecular pathobiology of gastrointestinal malignancy and premalignancy. He invented molecular methods to detect loss of heterozygosity in tiny biopsies, triggering an avalanche of research on precancerous lesions. He was the first to comprehensively study coding region microsatellite instability, leading to the identification of several important tumor suppressor genes. He performed several groundbreaking genomic, epigenomic and bioinformatic studies of esophageal and colonic neoplasms, shifting the GI research paradigm toward genome-wide approaches. He directed an ambitious nationwide validation study of DNA methylation-based biomarkers for the prediction of neoplastic progression in Barrett’s esophagus. Dr. Meltzer founded and led the Aerodigestive Cancer and Biomarker Interdisciplinary Programs at the University of Maryland, also becoming associate director for core sciences at that school’s Cancer Center. He currently holds an endowed professorship and is the director of GI biomarker research at Johns Hopkins. The laboratory group focuses its efforts on the molecular genetics of gastrointestinal cancers and premalignant lesions, as well as on translational research to improve early detection, prognostic evaluation, and treatment of these conditions. Below, some examples of this work are described.

Under the division of Maternal-Fetal Medicine, our Cardio-Obstetric research efforts seek to advance the field of gynecology through medical care and innovation. With a focus on the effect of heart conditions on pregnancy and the ways in which pregnancy can put stress on your heart and circulatory system, our goal in this multi-disciplinary research is that our findings may lead to the development of new treatments or preventative therapies for patients and their babies to better manage a heart condition during pregnancy.

The Cardiology Bioengineering Laboratory, located in the Johns Hopkins Hospital, focuses on the applications of advanced imaging techniques for arrhythmia management. The primary limitation of current fluoroscopy-guided techniques for ablation of cardiac arrhythmia is the inability to visualize soft tissues and 3-dimensional anatomic relationships. Implementation of alternative advanced modalities has the potential to improve complex ablation procedures by guiding catheter placement, visualizing abnormal scar tissue, reducing procedural time devoted to mapping, and eliminating patient and operator exposure to radiation. Active projects include • Physiological differences between isolated hearts in ventricular fibrillation and pulseless electrical activity • Successful ablation sites in ischemic ventricular tachycardia in a porcine model and the correlation to magnetic resonance imaging (MRI) • MRI-guided radiofrequency ablation of canine atrial fibrillation, and diagnosis and intervention for arrhythmias • Physiological and metabolic effects of interruptions in chest compressions during cardiopulmonary resuscitation Henry Halperin, MD, is co-director of the Johns Hopkins Imaging Institute of Excellence and a professor of medicine, radiology and biomedical engineering. Menekhem M. Zviman, PhD is the laboratory manager.

The research mission of the Zackary Berger Lab is to bridge evidence-based medicine and shared decision-making in the context of patient-centered care. Lab studies investigate how to accomplish this in the common case of uncertainty, while seeking to clarify the ethics of decision-making and empirically describe how shared decision-making is and should be done. Zackary Berger, MD, PhD, is an assistant professor in the Division of General Internal Medicine at the Johns Hopkins School of Medicine. In addition to his work as an internist and primary care physician, Dr. Berger is an associate faculty member in the Berman Institute of Bioethics, and core faculty in the Evidence Based Practice Center as well as the Center for Health Services and Outcomes Research.

Research in the Zishan Siddiqui Lab focuses on patient-centered care and satisfaction, preoperative medicine and clinical reasoning. We are also interested in international medicine. In a previous collaboration with Daniel Brotman, M.D., we discovered that hospital renovations do not improve patient satisfaction.

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.

Research in the Deborah Schwengel Lab focuses on perioperative care of pediatric patients with obstructive sleep apnea as well as anesthetic care for patients undergoing ethanol embolization of vascular malformations. Our team also explores topics within graduate medical education. In this field, our work has involved evaluating both an educational curriculum and a disaster preparedness curriculum for anesthesiology residents. We also have a long-standing interest in international adoption medicine.