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The Atul Bedi Lab in the Head and Neck cancer research program provides fundamental insights into the molecular determinants and mechanisms by which tumor cells evade death signals entrained by the immune system and anticancer agents. Their recent studies show that tumor-induced immune tolerance limits the in vivo anti-tumor efficacy of tumor-targeted antibodies and that the tumor cell-autonomous expression of transforming growth factor-b (TGF-b) is a key molecular determinant of the de novo or acquired resistance of cancers to EGFR-targeted antibody. Their laboratory has developed novel bi-functional antibody-based strategies to simultaneously counteract immune tolerance in the tumor microenvironment and to enhance the anti-tumor efficacy of targeted antibody therapies for the treatment of cancer.
The Brennen laboratory takes a rigorous, multi-disciplinary, team-based approach towards developing innovative therapeutic and prognostic strategies for prostate cancer with an emphasis on exploiting vulnerabilities within the tumor microenvironment towards this goal. To accomplish this goal, we are strategically pursuing novel therapeutic platforms, including stromal-targeted prodrugs, protoxins, and radiolabeled antibodies, in addition to cell-based therapy and drug delivery; all of which are designed to reduce toxicity to peripheral non-target tissue (i.e. side effects) while maximizing anti-tumor efficacy (i.e. therapeutic benefit). Currently, many of these strategies are focused on overcoming stromal barriers to anti-tumor immune responses such that men suffering from prostate cancer can share in the immense, revolutionary power of immunotherapy that is transforming care for many with advanced disease in other tumor types previously thought to be unmanageable using conventional ap...proaches. Unfortunately, prostate cancer has largely proven refractory to these powerful approaches thus far and requires novel mono- or combinatorial treatment strategies to unleash the full potential of the immune system and generate personalized anti-tumor responses with the capability of producing long-term durable responses or even cures in these men. view less
Johns Hopkins is a member of the Specialized Program of Research Excellence (SPORE) in Cervical Cancer. With a $11.5 million grant from the National Cancer Institute, we are conducting lab, translational and clinical studies to prevent and treat cervical cancers. Previous studies have identified connections between immune system genes and HPV16. Current projects include the development of next-generation HPV vaccines to control HPV-associated precursor lesions and invasive cancer. Our dedicated researchers are working to extend the techniques used in HPV vaccine development to the creation of vaccines targeting other cancers with defined tumor antigens.
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
The Erika Darrah Lab is primarily interested in the mechanisms underlying the development and progression of autoimmunity in rheumatoid arthritis (RA), with a particular focus on the peptidyl arginine deiminase (PAD) enzymes. We’re focused on understanding the development of PAD4-activating autoantibodies over time and how they contribute to the development of erosive disease. Studies are underway to determine if the newly discovered antibody is mimicking a naturally occurring PAD4 binding partner and to identify potentially pro-inflammatory effects of citrullinated proteins on effector cells of the immune system.
Work in the Joel Blankson Lab explores the mechanism of control of HIV-1 replication in a cohort of patients known as elite controllers or elite suppressors. These patients are HIV-1 seropositive but maintain levels of viremia that are below the limit of detection of standard clinical assays. We feel that elite suppressors represent a potential model for a therapeutic HIV vaccine. Our central hypothesis is that many of these patients are infected with fully replication-competent HIV-1 isolates that are held in check by the immune system. To test this hypothesis, we are studying many different host and viral factors in these patients.
Dr. Sohn's lab is interested in understanding how biological stress-sensors are assembled, detect danger signals and initiate stress response.
Innate immunity is the first line of defense against invading pathogens in higher eukaryotes. We are using in vitro quantitative biochemical assays and mutagenesis and x-ray crystallography to investigate the underlying operating principles of inflammasomes, a component of the innate immune system, to better understand biological stress sensors.
Our laboratory conducts basic and translational research aimed at better understanding the pathogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventi...ng maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task. view more
Research in the Paul Rothman Lab has focused on cytokines. We’ve investigated the role these molecules play in the normal development of blood cells as well as the abnormal blood-cell development that leads to leukemia. We’ve also studied the function of cytokines in immune system responses to asthma and allergies.
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
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 Hillel Laboratory at Johns Hopkins investigates inflammatory, genetic, and molecular factors involved with laryngotracheal stenosis, or scar formation in the airway. Specifically, we are examining the interrelationship between genetics, the immune system, bacteria, and scar formation in the airway. The lab has developed unique models to study laryngotracheal stenosis and test drugs that may halt the progression of scar or reverse scar formation. We are also developing a drug-eluting stent to treat patients with laryngotracheal stenosis.
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