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Andrea Cox Lab
Research in the Andrea Cox Lab explores the immune response in chronic viral infections, with a focus on HIV and the hepatitis C virus (HCV). In our studies, we examine the role of the immune response upon exposure to HCV by examining responses to HCV in a longitudinal, prospective group of high-risk individuals. This enables us to compare the innate, humoral and cellular immune responses to infection with clearance versus persistence. Through our findings, we seek to identify mechanisms of protective immunity against HCV infection and improve HCV vaccine design.
Drew Pardoll Lab
The Pardoll Lab focuses on the regulation of antigen-specific T cell responses and studies approaches to modify these responses for immunotherapy. Pardoll has a particular interest in cancer immunology and his lab’s studies on basic immunologic mechanisms have led to the development and design of a number of cancer vaccines and discovery of key checkpoint ligands and receptors, such as PD-L2, LAG-3 and neuritin, many of which are being targeted clinically.
Our primary pursuits are discovering and elucidating new molecules that regulate immune responses, investigating the biology of regulatory T cells, and better understanding the specific biochemical signatures that allow a patient’s T cells to selectively target cancer cells.
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
Franco D’Alessio Lab
The Franco D’Alessio Lab investigates key topics within the fields of critical care, internal and pulmonary medicine. We primarily explore immunological determinants of acute lung inflammation and repair. Our lab also investigates age-dependent lung immune response in patients with acute lung injury and acute respiratory distress syndrome (ARDS), regulatory T-cells in lung injury and repair, and modulation of alveolar macrophage innate immune response in ARDS.
The Ivan Borrello Lab focuses on the development of a novel approach of adoptive T cell therapy utilizing marrow-infiltrating lymphocytes (MILs) as a more tumor-specific T cell approach. This has led to establishing the first adoptive T cell trials at Johns Hopkins and an exploration of this approach in other diseases, including nonhematologic malignancies. The lab also examines strategies for treating minimal residual disease (MRD) in myeloma with the combination of immune modulation and whole cell-based vaccines.
Joseph Margolick Lab
Research in the Joseph Margolick Lab focuses on the many effects of HIV/AIDS on human health. We are particularly interested in the mechanisms of T-cell loss and preservation among people infected with HIV and the evaluation of human immune functions.
Maureen Horton Lab
The Maureen Horton Lab conducts research on pulmonary fibrosis through the use of both preclinical models and human trials. Our studies have helped to develop novel, genetic, tissue-specific models of immune dysfunction, which have aided in defining the immune regulation of fibrosis and in the development of treatment strategies. We have used T-cell skewing immunotherapy to prevent and reverse chemical-induced lung fibrosis and have conducted clinical trials for idiopathic pulmonary fibrosis (IPF), which led to one of the first treatments that helped to improve quality of life in IPF patients.
Michael Edidin Lab
The Michael Edidin Lab studies membrane dynamics and organization in cells from lymphocytes to epithelial cells using biochemistry, biophysics (especially fluorescence methods), cell biology, biochemistry and immunology. We are interested in transplantation immunology, particularly in the cell biology of class I MHC molecules, and are working to understand the relationship between plasma membrane biophysics and antigen presentation by MHC molecules. We are currently studying the clustering of T cell receptors for the antigen TCR.
Robert Siliciano Laboratory
Research in the Robert Siliciano Laboratory focuses on HIV and antiretroviral therapy (ART). ART consists of combinations of three drugs that inhibit specific steps in the virus life cycle. Though linked to reduced morbidity and mortality rates, ART is not curative. Through our research related to latently infected cells, we've shown that eradicating HIV-1 infection with ART alone is impossible due to the latent reservoir for HIV-1 in resting CD4+ T cells.
Our laboratory characterized the different forms of HIV-1 that persist in patients on ART. Currently, we are searching for and evaluating drugs that target the latent reservoir. We are also developing assays that can be used to monitor the elimination of this reservoir. We are also interested in the basic pharmacodynamic principles that explain how antiretroviral drugs work. We have recently discovered why certain classes of antiretroviral drugs are so effective at inhibiting viral replication. We are using this discovery along w...ith experimental and computational approaches to develop improved therapies for HIV-1 infection and to understand and prevent drug resistance. Finally, we are studying the immunology of HIV-1 infection, and in particular, the ability of some patients to control the infection without ART. view more
Effective immune responses are critical for control of a variety of infectious disease including bacterial, viral and protozoan infections as well as in protection from development of tumors. Central to the development of an effective immune response is the T lymphocyte which, as part of the adaptive immune system, is central in achieving sterilization and long lasting immunity. While the normal immune responses is tightly regulated there are also notable defects leading to pathologic diseases. Inactivity of tumor antigen-specific T cells, either by suppression or passive ignorance allows tumors to grow and eventually actively suppress the immune response. Conversely, hyperactivation of antigen-specific T cells to self antigens is the underlying basis for many autoimmune diseases including: multiple sclerosis; arthritis; and diabetes. Secondary to their central role in a wide variety of physiologic and pathophysiologic responses my lab takes a broad-based approach to studying T cell re...sponses. view more
Sean Leng Lab
The Sean Leng Lab studies the biology of healthy aging. Specific projects focus on chronic inflammation in late-life decline; immunosenescence and its relationship to the basic biological and physiological changes related to aging and frailty in the human immune system; and T-cell repertoire analysis.
The Soloski Lab works to understand how infection can lead to the development of chronic immune-mediated diseases. Our lab studies the role of cellular immune response in controlling infection with gram-negative bacterial pathogens, such as Salmonella typhimurium. Our work has recently focused on the role of the intestinal mucosal immune compartment in controlling oral infection. This effort has identified a new unrecognized subset of T cells residing within the epithelial barrier that expands following infection. Current efforts concentrate on understanding the recognition properties and effector function of this T cell subset and determining if an analogous population exists in the human mucosa. We also strive to understand the human host immune response to infection with Borrelia burgdorfer, the causative agent of Lyme disease.
Our research interest is crystalized into three main areas:
1. Type-1 diabetes - Our focus is on understanding how the Fas death pathway regulates the disease and how extracted information can be used to protect high risk individuals and those with new-onset disease.
2. Type 2 diabetes and Obesity - Our lab is studying the role of heparan sulfate proteoglycans (HSPG) in regulating body fat and glucose clearance.
3. Double negative ??T cells - Our studies suggest a critical role for these cells in protecting kidneys from Ischemia reperfusion injury (IRI). Our current focus is understanding their origin and physiological functions.