Normal and neoplastic cells respond to genome integrity threats in a variety of different ways. Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment. Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to carcinogens. Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies. Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections. A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer.

The Raman laboratory is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The focus of the laboratory is bench-to-bed side cancer research. We integrate molecular and cellular biology, developmental biology, cancer biology, molecular imaging techniques to study cancer formation and progression. Many of the projects in the lab investigate dysregulated genes in cancer and the translatability of this information to a clinical setting. One such project is to functionally decipher the role of a RNA helicase gene, DDX3, in the biogenesis of multiple cancer types such as breast, lung, brain, sarcoma, colorectal and prostate. Additionally, using a rational drug design approach, a small molecule inhibitor of DDX3 (RK-33) was synthesized and its potential for clinical translation is being investigated.

The Laboratory for computational Motor Control studies movement control in humans, including healthy people and people with neurological diseases. We use robotics, brain stimulation and neuroimaging to study brain function. Our long-term goals are to use mathematics to understand: 1) the basic function of the motor structures of the brain including the cerebellum, the basal ganglia and the motor cortex; and 2) the relationship between how our brain controls our movements and how it controls our decisions.

Research in the Nicholas Dalesio Lab is currently examining pre-surgical predictors of post-surgical respiratory complications in children with obstructive sleep apnea and sleep-disordered breathing; the impact of anesthesia and pharmacological agents on upper airway physiology; and techniques for pediatric airway imaging.

Directed by Debraj “Raj” Mukherjee, MD, MPH, the laboratory focuses on improving access to care, reducing disparities, maximizing surgical outcomes, and optimizing quality of life for patients with brain and skull base tumors.

The laboratory achieves these aims by creating and analyzing institutional and national databases, developing and validating novel patient-centered quality of life instruments, leveraging machine learning and artificial intelligence platforms to risk-stratify vulnerable patient populations, and designing novel surgical trials to push the boundaries of neurosurgical innovation.

Our research also investigates novel approaches to improve neurosurgical medical education including studying the utility of video-based surgical coaching and the design of new operative instrumentation.

The Nicholas Flavahan Lab primarily researches the cellular interactions and subcellular signaling pathways that control normal vascular function and regulate the initiation of vascular disease. We use biochemical and molecular analyses of cellular mediators and cell signaling mechanisms in cultured vascular cells, while also conducting physiological assessments and fluorescent microscopic imaging of signaling systems in isolated blood vessels. A major component of our research involves aterioles, tiny blood vessles that are responsible for controlling the peripheral resistance of the cardiovascular system, which help determine organ blood flow.

Our laboratory pioneers innovations at the intersection of precision neurology, neuroengineering, artificial intelligence, and data science. We develop advanced neural-AI interfaces, autonomous wearable neurotechnologies, and immersive augmented and virtual reality platforms incorporating novel multimodal neuron-sensing technologies designed to personalize diagnostics, enhance therapeutic interventions, and optimize neurological rehabilitation. Leveraging computational neuroscience, AI, and applied data science, we generate robust digital biomarkers to monitor and treat neurologic diseases in real-time. Through interdisciplinary collaborations, we aim to transform clinical practice by providing precise, interactive, and personalized neurologic care that dramatically improves patient outcomes.

The Johns Hopkins Center for Global NCD Research and Training consists of faculty, fellows, and students from institutions across the United States and around the globe. Our mission is to conduct high-quality research and training for the prevention and control of non-communicable diseases in low- and middle-income countries (LMIC), with an aim to build local capacity through partnerships with local institutions and communities. Our current projects encompass subject matters ranging from clean cookstoves to mental health and involve sites in Peru, Uganda, Nepal, and Bangladesh. The burden of NCDs in LMICs is growing rapidly as a result of population aging, rapid unplanned urbanization, and the globalization of unhealthy lifestyles. We envision a robust and sustainable community of NCD researchers and trainees in both high and low income settings dedicated to improving health and well-being for all.

How do brain dynamics give rise to our sensory experience of the world? The O'Connor lab works to answer this question by taking advantage of the fact that key architectural features of the mammalian brain are similar across species. This allows us to leverage the power of mouse genetics to monitor and manipulate genetically and functionally defined brain circuits during perception. We train mice to perform simple perceptual tasks. By using quantitative behavior, optogenetic and chemical-genetic gain- and loss-of-function perturbations, in vivo two-photon imaging, and electrophysiology, we assemble a description of the relationship between neural circuit function and perception. We work in the mouse tactile system to capitalize on an accessible mammalian circuit with a precise mapping between the sensory periphery and multiple brain areas. Our mission is to reveal the neural circuit foundations of sensory perception; to provide a framework to understand how circuit dysfunction causes mental and behavioral aspects of neuropsychiatric illness; and to help others fulfill creative potential and contribute to human knowledge.

The Leucker Laboratory is a translational cardiovascular research program dedicated to understanding the mechanisms underlying residual atherosclerotic cardiovascular disease risk and developing innovative strategies for cardiovascular prevention. Our work integrates human vascular biology, advanced cardiovascular imaging, epidemiology, and clinical trials to uncover the pathways linking inflammation, lipoproteins, endothelial dysfunction, and cardiometabolic disease to cardiovascular outcomes.