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The Advanced Optics Lab uses innovative optical tools, including laser-based nanotechnologies, to understand cell motility and the regulation of cell shape. We pioneered laser-based nanotechnologies, including optical tweezers, nanotracking, and laser-tracking microrheology. Applications range from physics, pharmaceutical delivery by phagocytosis (cell and tissue engineering), bacterial pathogens important in human disease and cell division.
Other projects in the lab are related to microscopy, specifically combining fluorescence and electron microscopy to view images of the subcellular structure around proteins.
Researchers in the Ami Shah Lab study scleroderma and Raynaud’s phenomenon. We examine the relationship between cancer and scleroderma, with a focus on how and if cancer causes scleroderma to develop in some patients. We are currently conducting clinical research to study ways to detect cardiopulmonary complications in patients with scleroderma, biological and imaging markers of Raynaud’s phenomenon, and drugs that improve aspects of scleroderma.
Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.
Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets a...ppear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.
Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
• Ion channel biology and arrhythmias
• Cardiac pacemaker physiology and disease
• Molecular physiology of CaMKII
• Myocardial and mitochondrial metabolism
• CaMKII and reactive oxygen species in asthma
Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital. view more
The Brady Maher Laboratory is interested in understanding the cellular and circuit pathophysiology that underlies neurodevelopmental and psychiatric disorders. Our lab focuses on trying to understand the function of genes that are associated with neurodevelopment problems by manipulating their expression level in utero during the peak of cortical development. We then use a variety of approaches and technologies to identify resulting phenotypes and molecular mechanisms including cell and molecular biology, optogenetics, imaging and electrophysiology.
Current projects in the lab are focused on understanding the function of transcription factor 4 (TCF4), a clinically pleiotropic gene. Genome-wide association studies have identified genetic variants of TCF4 that are associated with schizophrenia, while autosomal dominant mutations in TCF4 result in Pitt Hopkins syndrome. Using our model system, we have identified several interesting electrophysiological and cell biological phenotypes as...sociated with altering the expression of TCF4 in utero. We hypothesize that these phenotypes represent cellular pathophysiology related to these disorders and by understanding the molecular mechanisms responsible for these phenotypes we expect to identify therapeutic targets for drug development.
Research in the Caleb Alexander Lab examines prescription drug use. This includes studies of population-based patterns and determinants of pharmaceutical use, clinical decision-making about prescription drugs, and the effect of changes in regulatory and payment policies on pharmaceutical utilization. We have special expertise in conducting survey-based studies and analyzing secondary data sources, including administrative claims, the Medical Expenditure Panel Survey and the National Ambulatory Medical Care Survey.
The Center for Nanomedicine engineers drug and gene delivery technologies that have significant implications for the prevention, treatment and cure of many major diseases facing the world today. Specifically, we are focusing on the eye, central nervous system, respiratory system, women's health, gastrointestinal system, cancer, and inflammation.
We are a unique translational nanotechnology effort located that brings together engineers, scientists and clinicians working under one roof on translation of novel drug and gene delivery technologies
Charles W. Flexner Laboratory
A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to measure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory.
B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacok...inetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms. view more
Craig W. Hendrix Lab
Research in the Craig W. Hendrix Lab concentrates on the chemoprevention of HIV infection, clinical pharmacology of antiviral drugs, drug interactions, and oral, topical and injectable HIV microbicide development. Our lab conducts small, intensive sampling studies of PK and PD of drugs for HIV prevention with a focus on developing methods to better understand HIV and drug distribution in the male genital tract, female genital tract and lower gastrointestinal tract. We also support numerous HIV pre-exposure prophylaxis development studies from phase I to phase III, largely as leader of the Pharmacology Core Laboratory of both the Microbicide Trial Network and HIV Prevention Trials Network.
The Dölen lab studies the synaptic and circuit mechanisms that enable social behaviors. We use a variety of techniques including whole cell patch clamp electrophysiology, viral mediated gene transfer, optogenetics, and behavior. We are also interested in understanding how these synaptic and circuit mechanisms are disrupted in autism and schizophrenia, diseases which are characterized by social cognition deficits. More recently we have become interested in the therapeutic potential of psychedelic drugs for diseases like addiction and PTSD that respond to social influence or are aggravated by social injury, We are currently using both transgenic mouse and octopus to model disease.
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 more