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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
Ruth Faden Lab
Research in the Ruth Faden Lab focuses on biomedical ethics and health policy. Our specific areas of interest include justice theory; national and global challenges in learning health care systems, health-system design and priority setting; access global investments benefits in biomedical research; and ethical challenges in biomedical science and women’s health.
Ryuya Fukunaga Lab
The Fukunaga Lab uses multidisciplinary approaches to understand the cell biology, biogenesis and function of small silencing RNAs from the atomic to the organismal level.
The lab studies how small silencing RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), are produced and how they function. Mutations in the small RNA genes or in the genes involved in the RNA pathways cause many diseases, including cancers. We use a combination of biochemistry, biophysics, fly genetics, cell culture, X-ray crystallography and next-generation sequencing to answer fundamental biological questions and also potentially lead to therapeutic applications to human diseases.
Our lab is focused on using comprehensive gene expression, methylation and sequencing and metabolomics analysis to identify alterations in breast cancer, and exploiting these for early detection and therapy. Among deferentially expressed genes, our lab has focused on the HOX genes. HOX genes are intimately involved in the development of resistance to both chemotherapy and to agents targeting the estrogen receptor. Our work explores the alternate pathways that are activated by HOX proteins leading to this resistance and novel treatments to overcome resistance in both tissue culture and xenograft models. In addition, epigenetically silenced genes and a metabolic reprogramming in tumors also trigger novel early detection and therapeutic strategies. We are testing the utility of differentiation therapy through reactivating RAR-beta in breast cancer using histone deacetylase inhibitors with great success. Also, we are targeting enzymes involved in gluconeogenesis and glycolysis with small ...molecule FDA-approved antimetabolites to achieve antitumor effects. view more
The Shanthini Sockanathan Laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating neuronal and glial differentiation in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve the...se questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior. view less
Shyam Sundar Biswal Lab
xResearch in the Shyam Biswal Lab focuses on therapeutic resistance of cancer due to a gain-of-function mutation in transcription factor Nrf2. Using patient-derived xenografts in humanized immunocompetent mice and GEM models, we aim to understand the mechanisms of oncogenic cooperation and metabolic adaptation in cancer cells. We’re also investigating the systemic and pulmonary effects of air pollution as well as the health effects of recent tobacco products, such as electronic cigarettes and water pipes.
Dr. Yegnasubramanian directs a Laboratory of Cancer Molecular Genetics and Epigenetics at the Sidney Kimmel Comprehensive Cancer Center (SKCCC), and is also the Director of the SKCCC Next Generation Sequencing Center.
Our lab research is focused on understanding the complex interplay between genetic and epigenetic alterations in carcinogenesis and disease progression, and to exploit this understanding in developing novel biomarkers for diagnosis and risk stratification as well as in identifying targets for therapeutic intervention.
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 Arking Lab
The Arking Lab studies the genomics of complex human disease, with the primary goal of identifying and characterizing genetics variants that modify risk for human disease. The group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. The lab is currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify specific genetic influences of disease.
The Arking Lab is actively involved in researching:
• autism, a childhood neuropsychiatric disorder
• cardiovascular genomics, with a focus on electrophysiology and sudden cardiac death (SCD)
• electrophysiology is the study of the flow of ions in biological tissues
Dan E. Arking, PhD, is an associate professor at the McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, D...ivision of Cardiology, Johns Hopkins University. view more
The Bigos Lab
The Bigos Lab focuses on a Precision Medicine approach to the treatment of psychiatric illness. In addition, this lab employs functional neuroimaging and genetics as biomarkers in neuropsychiatric drug development. A recent study used functional MRI to test the neural effects of a drug with the potential to treat cognitive dysfunction in schizophrenia. Other studies aim to identify patient-specific variables including sex, race, and genetics that impact drug clearance and clinical response to better select and dose antipsychotics and antidepressants.