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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. view more
Molecular and Comparative Pathobiology
Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.
Our research laboratory is staffed by a dedicated and experienced team of sleep scientists, fellows, technicians, engineers, and students. Currently, we are focused on the following areas:
-Novel treatments for sleep apnea using electrical and nerve stimulation and chemogenetic techniques
-Cardiovascular and metabolic effects of sleep apnea and hypoxia
-Leptin and its impact on breathing and cardiovascular physiology
-Sleep disordered breathing at high altitude
-Dietary impacts on asthma
The Stivers Lab is broadly interested in the biology of the RNA base uracil when it is present in DNA. Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. We use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and HIV-1 pathogenesis.
Susheel Patil Lab
Research in the Susheel Patil Lab focuses on the origination and development obstructive sleep apnea (OSA). Specifically, we’re interested in how obesity, adipokines and inflammation affect mechanisms that contribute to upper airway collapsibility. We’ve studied various patient groups affected by OSA, including patients who've had bariatric surgery, are HIV-infected or have non-alcoholic fatty liver disease.
Tamara O'Connor Lab
The O'Connor Lab studies the molecular basis of infectious disease using Legionella pneumophila pathogenesis as a model system.
We are looking at the network of molecular interactions acting at the host-pathogen interface. Specifically, we use L. pneumophila pathogenesis to examine the numerous mechanisms by which an intracellular bacterial pathogen can establish infection, how it exploits host cell machinery to accomplish this, and how individual proteins and their component pathways coordinately contribute to disease.
We are also studying the role of environmental hosts in the evolution of human pathogens. Using genetics and functional genomics, we compare and contrast the repertoires of virulence proteins required for growth in a broad assortment of hosts, how the network of molecular interactions differs between hosts, and the mechanisms by which L. pneumophila copes with this variation.
The Ted Dawson Laboratory uses genetic, cell biological and biochemical approaches to explore the pathogenesis of Parkinson's disease (PD) and other neurologic disorders. We also investigate several discrete mechanisms involved in cell death, including the role of nitric oxide as an endogenous messenger, the function of poly (ADP-ribose) polymerase-1 and apoptosis inducing factor in cell death, and how endogenous cell survival mechanisms protect neurons from death.
The Cihakova research laboratory is an immunology laboratory dedicated to the investigation of autoimmune diseases. Our most active research is focused on myocarditis and dilated cardiomyopathy. We expanded our interest in inflammatory heart diseases to include the study of immune mechanisms driving pericarditis and myocardial infarction. In addition, we are interested in the pathogenesis of a broad range of autoimmune diseases such as, Sjogren's syndrome, congenital complete heart block, and APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). Through several collaborative projects we also investigate rheumatoid arthritis and the immune components of schizophrenia.
David Hackam’s laboratory focuses on necrotizing enterocolitis (NEC), a devastating disease of premature infants and the leading cause of death and disability from gastrointestinal disease in newborns.
The disease strikes acutely and without warning, causing sudden death of the small and large intestines. In severe cases, tiny patients with the disease are either dying or dead from overwhelming sepsis within 24 hours. Surgical treatment to remove most of the affected gut results in lifelong short gut (short bowel) syndrome.
The Hackam Lab has identified a critical role for the innate immune receptor toll-like receptor 4 (TLR4) in the pathogenesis of necrotizing enterocolitis. The lab has shown that TLR4 regulates the development of the disease by tipping the balance between injury and repair in the stressed intestine of the premature infant. Developing an Artificial Intestine A key goal is to create, in the laboratory, new intestines made from patients’ own cells, which can then ...be implanted into the patient to restore normal digestive function. This innovative design could transform child development and quality of life in necrotizing enterocolitis survivors without the risks of conventional donor transplant. view more
The mission of the Transplant and Oncology Infectious Diseases (TOID) Center is to expand institutional expertise in clinical and academic activities focused on infectious complications in transplant (solid organ and stem cell) and oncology patients at Johns Hopkins medical institutions. Key efforts include developing standardized algorithms for the prevention and treatment of infections in these vulnerable patients and to establish an expanded infrastructure to facilitate clinical and translational studies at TOID. Current research projects focus on diagnostics for invasive fungal infections and specialized studies of the pathogenesis of candidiasis and aspergillosis.