Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, we study the simian immunodeficiency virus (SIV) to determine the molecular basis for the development of HIV CNS, pulmonary and cardiac disease. Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. We are also interested in studies of lentivirus replication in macrophages and astrocytes and their role in the development of disease. These studies have led us to identify the viral genes that are important in neurovirulence of SIV and the development of CNS disease including NEF and the TM portion of ENV. The mechanisms of the action of these proteins in the CNS are complex and are under investigation. We have also developed a rapid, consistent SIV/macaque model in which we can test the ability of various antiviral and neuroprotective agents to reduce the severity of CNS and pulmonary disease.

The Joseph Mankowski Lab studies the immunopathogenesis of HIV infection using the SIV/macaque model. Our researchers use a multidisciplinary approach to dissect the mechanism underlying HIV-induced nervous system and cardiac diseases. Additionally, we study the role that host genetics play in HIV-associated cognitive disorders.

The David Graham Lab studies the consequences of HIV interactions with the immune system, the resulting pathogenesis and how to sabotage these interactions. We apply advanced technologies like mass spectrometry to dissect processes at the molecular level. We are also actively involved in cardiovascular research and studies the ways proteins are organized into functional units in different cell types of the heart. Major projects in our lab are organized into three major areas: (1) H/SIV pathogenesis and neuropathogenesis, (2) Cardiovascular disease, and (3) High technology development

We investigate the brain networks and neurotransmitters involved in symptoms of movement disorders, such as Parkinson's disease, and the mechanisms by which modulating these networks through electrical stimulation affects these symptoms. We are particularly interested in the mechanisms through which neuromodulation therapies like deep brain stimulation affect non-motor brain functions, such as cognitive function and mood. We use imaging of specific neurotransmitters, such as acetylcholine and dopamine, to understand the changes in brain chemistry associated with the clinical effects of deep brain stimulation and to predict which patients are likely to have changes in non-motor symptoms following DBS. Through collaborations with our neurosurgery colleagues, we explore brain function by making recordings during DBS surgery during motor and non-motor tasks. Dr. Mills collaborates with researchers in the Department of Neurosurgery, the Division of Geriatric and Neuropsychiatry in the Department of Psychiatry and Behavioral Sciences and in the Division of Nuclear Medicine within the Department of Radiology to translate neuroimaging and neurophysiology findings into clinical applications.

Research in the Alfredo Kirkwood Laboratory is directed toward elucidating the basic mechanisms by which visual experience can modify cortical connections in the visual cortex and how those mechanisms are regulated. In visual cortical slices, we investigate two forms of activity-dependent synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). These two forms of synaptic plasticity are currently the most comprehensive models of the elementary mechanisms underlying naturally occurring plasticity. We are currently focused on how synaptic inhibition and the action of neuromodulators regulate the induction of LTP and LTD during development. We hope to gain a better understanding of how naturally occurring plasticity is regulated.

The Aliaksei Pustavoitau Lab conducts research on models and mechanisms of impaired consciousness in patients who have suffered acute brain injury. Examples of our work include a study on the mechanisms of neurologic failure in critical illness and another on the use of intensivist-driven ultrasound at the PICU bedside. We also have a longstanding interest in patient safety and quality of care in the ICU setting.

The ALS Center for Cell Therapy and Regeneration Research at Johns Hopkins is committed to identifying the causes of the neurodegenerative disease, amyotrophic lateral sclerosis (ALS), and discovering new and effective treatment options. At the ALS Center, Johns Hopkins researchers work with other investigators, including those at the Robert Packard Center for ALS Research at Johns Hopkins and clinicians within the Johns Hopkins ALS Clinic to aggressively take groundbreaking scientific discoveries and turn them into clinical applications that will improve the quality of life of those diagnosed with ALS.

VISION: To make MRI more equitable and inclusive

MISSION: To develop and deploy MRI tools and methods to enable accessible imaging of underserved populations

The main focus of Dr. Gilotra's research is understanding the pathophysiology and outcomes in inflammatory cardiomyopathies including myocarditis and sarcoidosis, as well as improvement of heart failure patient care through noninvasive hemodynamic monitoring and studying novel strategies to reduce heart failure hospitalizations. Additional investigations involve clinical research in advanced heart failure therapies including heart transplantation and mechanical circulatory support. Dr. Gilotra is the site Principal Investigator for the NIH/NHLBI funded Heart Failure Network trials.

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.