Our research is focused on understanding the basic mechanisms of programmed cell death in disease pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms. We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains.

The Pomerantz Laboratory studies the molecular machinery used by cells to interpret extracellular signals and transduce them to the nucleus to affect changes in gene expression. The accurate response to extracellular signals results in a cell's decision to proliferate, differentiate or die, and it's critical for normal development and physiology. The dysregulation of this machinery underlies the unwarranted expansion or destruction of cell numbers that occurs in human diseases like cancer, autoimmunity, hyperinflammatory states and neurodegenerative disease. Current studies in the lab focus on signaling pathways that are important in innate immunity, adaptive immunity and cancer, with particular focus on pathways that regulate the activity of the pleiotropic transcription factor NF-kB.

Research in the Justin Bailey Lab explores immune responses against hepatitis C virus (HCV), particularly neutralizing antibody responses, with the goal of guiding vaccine development against the virus. Recent studies have demonstrated that early and broad neutralizing antibody (nAb) responses against HCV are associated with HCV clearance, suggesting a key role for nAb in limiting HCV replication. The findings of this research will enhance understanding of how HIV infection may contribute to the lower rate of HCV clearance in HCV/HIV coinfected individuals, and the results could have implications for persistence of other viruses commonly occurring as coinfections with HIV.

Research in the Joseph Carrese Lab focuses on clinical ethics and professionalism, with a particular interest in medical education and examining ethical issues in the context of cultural diversity. We collaborate with colleagues to design, implement and evaluate educational curricula addressing ethics and professionalism issues in clinical practice.

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.

Dr. Hua's research has centered on the development of novel MRI technologies for in vivo functional and physiological imaging in the brain, and the application of such methods for studies in healthy and diseased brains. These include the development of human and animal MRI methods to measure functional brain activities, cerebral perfusion and oxygen metabolism at high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is particularly interested in novel MRI approaches to image small blood and lymphatic vessels in the brain. Collaborating with clinical investigators, these techniques have been applied 1) to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntingdon's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD) and mental disorders such as schizophrenia; and 2) to map brain functions and cerebrovascular reactivity for presurgical planning in patients with vascular malformations, brain tumors and epilepsy.

Research in the Janet Record Lab focuses on medical education and patient-centered care. We’re currently developing a curriculum for internal medicine residents in the inpatient general medicine service setting. The curriculum teaches residents to use hand-carried ultrasound for imaging the inferior vena cava to assess volume status.

Research in the Jeremy Greene Lab focuses on the history of disease and the ways that medical technologies affect our understanding of what it means to be sick, healthy, normal or abnormal. Particular areas of interest include 20th century clinical medicine, pharmaceuticals, medical technology, medical anthropology and global health.

Research in the Jennifer Lee-Summers Lab explores cerebrovascular autoregulation, particularly during anesthesia. Our previous studies have examined cerebrovascular autoregulation and blood flow in patients with hypothermia, in neonatal patients with hypoxic-ischemic encephalopathy and in pediatric patients with moyamoya disease.

Research in the Jodi Segal Lab focuses on developing methodologies to use observational data to understand the use of new drugs, particularly drugs for treating diabetes, blood disorders and osteoporosis. We apply advanced methods for evidence-based review and meta-analysis, and—in collaboration with Johns Hopkins biostatisticians—we have developed new methodologies for observational research (using propensity scores to adjust for covariates that change over time) and methods to account for competing risks and heterogeneity of treatment effects in analyses.