Research in the Nicola Heller Lab focuses on the immunobiology of macrophages. Our team explore...s how these cells impact diseases with an inflammatory element, such as cancer, cardiovascular disease and obesity. Using a variety of techniques, including molecular and cellular biology, biochemistry, mouse models and more, we study the role of IL-4/IL-13 signaling in asthma and allergic disease, as well as the role of alternatively activated macrophages (AAM) in the pathogenesis of allergic inflammation. Currently, we are researching the links between asthma and obesity, with a focus on the roles of gender and race. view more

The Philip Wong Lab seeks to understand the molecular mechanisms and identification of new ther...apeutic targets of neurodegenerative diseases, particularly Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Taking advantage of discoveries of genes linked to these diseases (mutant APP and PS in familial AD and mutant SOD1, dynactin p150glued ALS4and ALS2 in familial ALS), our laboratory is taking a molecular/cellular approach, including transgenic, gene targeting and RNAi strategies in mice, to develop models that facilitate our understanding of pathogenesis of disease and the identification and validation of novel targets for mechanism-based therapeutics. Significantly, these mouse models are instrumental for study of disease mechanisms, as well as for design and testing of therapeutic strategies for AD and ALS. view more

The Jia lab performs basic and translational research into the mechanisms of and therapeutic st...rategy for viral and bacterial infection-induced inflammatory lung diseases, one of the leading causes of death in pulmonary diseases, especially for the ongoing pandemic of the SARS-CoV-2 mediated COVID-19. Our work has identified novel roles of Angiotensin-converting enzyme 2 (ACE2) in the inflammatory response to viral and bacterial lung infection and its complex contributions into the pathogenesis and disease progression and outcome of COVID-19. In seeking to translate these findings to clinical studies, we have been working on a collaboration with other investigators, developing novel diagnostic, preventive, and therapeutic tools in combating the devastating COVID-19, even in the era of effective vaccine prevention. These studies are funded by NIAID. view more

The Retinal Cell and Molecular Laboratory has three major areas of interest, each of which deal...s with some aspect of growth factor signaling and function in the retina and retinal pigmented epithelium (RPE): 1. Investigations aimed at gaining a better understanding of the pathogenesis of retinal and choroidal neovascularization and developing new ways to treat them.
2. Investigations aimed at understanding the molecular signals involved in retinal and RPE wound repair and scarring. The prototypical disease in this category is proliferative vitreoretinopathy and our laboratory is seeking to identify new treatments for it. 3. Investigations aimed at understanding why retinal degenerations occur and how they might be treated, with particular emphasis on neurotrophic factors. view more

Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of len...tivirus 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

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. view more

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. view more

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.
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The Ted Dawson Laboratory uses genetic, cell biological and biochemical approaches to explore t...he 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. view more

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. view more

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

Research in the Thomas Grader-Beck Lab aims to understand the pathogenesis of systemic autoimmu...ne diseases—particularly systemic lupus erythematosus (SLE) and Sjögren’s syndrome—by taking a translational approach. Autoantibodies (antibodies that target self-molecules) are believed to contribute significantly to the disease process. We are studying mechanisms that may make self-structures immunogenic. We theorize that certain post-translational antigen modifications, which can occur in infections or malignant transformation, result in the expression of neoepitopes that spread autoimmunity in the proper setting. The team has combined studies that employ a number of mouse strains, certain gene-deficient mice and human biological specimens. view more

Research in the Thomas Quinn Lab encompasses epidemiology, pathogenesis and clinical features o...f HIV/AIDS internationally, which includes the interaction between STDs and tropical diseases on the natural history and spread of HIV/AIDS in developing countries. Our recent research has examined the viral kinetics and transmission probabilities of HIV among discordant couples with the subsequent design and application of interventions, including therapy to prevent transmission of HIV. Molecular studies have mapped the molecular epidemic of HIV on a global basis, linking virologic changes to the spread of HIV and measuring the demographic impact of the epidemic. view more

The goals of the Translational neurobiology Laboratory are to understand the pathogenesis and c...ell death pathways in neurodegenerative disorders to reveal potential therapeutic targets for pharmaceutical intervention; to investigate endogenous survival pathways and try to induce these pathways to restore full function or replace lost neurons; and to identify biomarkers to mark disease function or replace lost neurons; and to identify biomarkers to mark disease progression and evaluate therapeutics. Our research projects focus on models of Huntington's disease and Parkinson's disease. We use a combination of cell biology and transgenic animal models of these diseases. view more

The William Bishai Laboratory studies the molecular pathogenesis of tuberculosis. The overall g...oal of our laboratory is to better understand tuberculosis pathogenesis and then to employ this understanding toward improved drugs, vaccines and diagnostics. Since Mycobacterium tuberculosis senses and adapts to a wide array of conditions during the disease process, it is clear that the regulation of expression of virulence factors plays an important role in pathogenesis. As a result, a theme of our research is to assess mycobacterial genes important in gene regulation. We are also interested in cell division in mycobacteria and the pathogenesis of caseation and cavitation. view more

Normal and neoplastic cells respond to genome integrity threats in a variety of different ways.... Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment.

Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to carcinogens.
Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies.

Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections.
A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer. view more