Dr. Rabb’s lab is involved in translational research aimed at understanding the molecular pathogenesis of kidney ischemia/reperfusion injury. The lab is interested in the development of novel treatments for kidney IRI.

Research in the Thomas Grader-Beck Lab aims to understand the pathogenesis of systemic autoimmune 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.

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.

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.

The Jia lab performs basic and translational research into the mechanisms of and therapeutic strategy 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.

The Lane laboratory is focused on understanding molecular mechanisms underlying chronic rhinosinusitis, particularly the pathogenesis of nasal polyps, as well as inflammation on the olfactory epithelium. Diverse techniques in molecular biology, immunology, and physiology are utilized to study epithelial cell innate immunity, olfactory loss, and response to viral infection. Ongoing work explores how epithelial cells of the sinuses and olfactory mucosa participate in the immune response and contribute to chronic inflammation. The lab creates and employs transgenic mouse models of chronic nasal/sinus inflammation to support research in this area. Collaborations are in place with the School of Public Health to explore mechanisms of anti-viral immunity in influenza and COVID-19.

The Alison Moliterno Lab studies the molecular pathogenesis of myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocytosis and idiopathic myelofibrosis. Our research is focused on the genetic and epigenetic lesions associated with MPDs, with the goal of improving diagnosis and treatment for these disorders.

Brendan Antiochos is a physician scientist in the Division of Rheumatology. His main interest is the role of the innate immune system in the pathogenesis of rheumatic diseases. Current work focuses on the identification of specific endogenous nucleic acids that drive pathogenic innate immune responses in these conditions. More information about his group and work can be found at his lab website.

Our research is focused on understanding the basic mechanisms of programmed cell death in disease pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms. We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains.

The Jean Kim Laboratory performs translational research in the area of chronic rhinosinusitis, with a niche interest in the pathogenesis of hyperplastic nasal polyposis. Studies encompass clinical research to basic wet laboratory research in studying the underlying immune and autoimmune mediated mechanism of polyp growth and perpetuation of disease. Human cell and tissue culture models are used. Techniques in the laboratory include cell and tissue culture, real time PCR, immunoblot, ELISA, flow cytometry, immunohistochemistry, electron microscopy, gene array analysis, and other molecular approaches including genetic knockdowns. Approaches used in Dr. Kim’s clinical study designs include prospective and retrospective analysis of patient outcomes and clinical biomarkers, as wells controlled clinical trials.