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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/p...rotein and protein/nucleic acid interactions, and in using microfluidics and single-molecule approaches for biochemical investigations of protein dynamics. view more
At the brain tumor laboratory, Henry Brem, M.D. and Betty Tyler, along with more than 350 trainees, have conducted scientific research, contributed to scientific literature, amended clinical practice, and illuminated new pathways for improving clinical outcomes.
The laboratory has advanced the understanding of gene therapy, angiogenesis, intracranial implantation of biodegradable polymers to treat malignant glioma, tumor genetics and proteomics, microchip drug delivery and drug resistance studies. Dr. Brem and his colleagues have designed and led many multi-institutional clinical trials to improve and expand the range of therapeutic options for patients with brain tumors.
The Machamer Lab is interested in the structure and function of the Golgi complex, an ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids in the secretory pathway. One goal of our research is to understand the role of this structure in Golgi function by targeting and function of resident Golgi proteins. The other research interest in the lab is the assembly mechanism of coronaviruses, enveloped viruses that bud into Golgi compartments. We are addressing how coronaviruses target their envelope proteins to Golgi membranes, and how they interact with each other at the virus assembly site. We are also exploring how coronaviruses are exocytosed after they bud into the Golgi lumen. Our long-term goal is to understand the advantages of intracellular assembly for coronaviruses.
Current projects include:
The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors.
This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.
The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen... based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed .
This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.
The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics. view less
The Shenderov Lab focuses on the elucidation of the mechanisms of immune response and resistance to immunotherapy in Prostate Cancer. This has led to clinical and basic research investigating the presumptive checkpoint inhibitor B7-H3.
In pursuit of understanding biomarkers or resistance and response, and regulatory molecules of immune response, we utilize artificial intelligence, immunogenomics, and spatial proteomics and transcriptomics in the laboratory and at the bedside using clinical trial correlative samples.
The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental problems in the fields of cardiac preconditioning and heart failure. Protein networks are perturbed in heart disease in a manner that correlates only weakly with changes in mRNA transcripts. Moreover, proteomic techniques afford the systematic assessment of post-translational modifications that regulate the activity of proteins responsible for every aspect of heart function from electrical excitation to contraction and metabolism. Understanding the status of protein networks in the diseased state is, therefore, key to discovering new therapies.
D. Brian Foster, Ph.D., is an assistant professor of medicine in the division of cardiology, and serves as Director of the Laboratory of Cardiovascular Biochemistry at the Johns Hopkins University School of Medicine.
The Frueh Laboratory uses nuclear magnetic resonance (NMR) to study how protein dynamics can be modulated and how active enzymatic systems can be conformed. Non-ribosomal peptide synthetases (NRPS) are large enzymatic systems that biosynthesize secondary metabolites, many of which are used by pharmaceutical scientists to produce drugs such as antibiotics or anticancer agents. Dr. Frueh's laboratory uses NMR to study inter- and intra-domain modifications that occur during the catalytic steps of NRPS. Dr. Frueh and his team are constantly developing new NMR techniques to study these complicated enzymatic systems.
The Fu Lab is a basic research lab that studies zinc transport, with a particular focus on which step in the zinc transport process may be modulated and how. Dr. Fu's lab uses parallel cell biology and proteomic approaches to understand how these physiochemical principles are applied to mammalian zinc transporters and integrated to the physiology of pancreatic beta cells. This research has implications for understanding how zinc transport is related to diabetes and insulin intake.
The Gabelli lab research is focused on structural, mechanistic and functional aspects of enzyme activation that play a role in the biology of human diseases such as cancer, parasitic infection and cardiovascular disease. Their work seeks to:
1. Understand how molecular events at the recognition level coordinate and trigger events in the cells
2. Translate structural and mechanistic information on protein:protein interactions at the cytoplasmic level into preventive and therapeutic treatment for human disease.
To achieve a comprehensive understanding, they are studying cytoplasmic protein-protein interactions involved in regulation of pathways such as PI3K and Sodium Voltage gated channels. Their research integrates structural biology and chemical biology and it is focused on drug discovery for targeted therapies.
The Zhu lab is focused on characterizing the activities of large collection of proteins, building signaling networks for better understanding the mechanisms of biological processes, and identifying biomarkers in human diseases and cancers. More specifically, our group is interested in analyzing protein posttranslational modifications, and identifying important components involved in transcription networks and host-pathogen interactions on the proteomics level, and biomarkers in human IBD diseases.