Javier Rangel-Moreno Lab
Javier Rangel-Moreno, Ph.D.
University of Rochester School of Medicine and Dentistry
Division of Allergy/Immunology and Rheumatology
Our scientific research is focused to define the long and short-term effects of gamma radiation on the induction of adaptive immunity against respiratory pathogens. In preliminary studies, supported by the Center for Medical Countermeasures against Radiation (CMCR) at the University of Rochester, we detected a sub-clinical effect on the structure of mediastinal lymph nodes, and impairment in the induction of humoral immunity against influenza viruses in adult mice exposed to gamma radiation in neonatal life. Although neonatal irradiation neither compromised viral clearance nor recovery from the influenza infection, we hypothesize that it will impair the induction of protective immunity against respiratory pathogens that are cleared by antibodies. Our goal is to identify pathways activated by radiation in secondary lymphoid organs (SLO), which will lead to the identification of novel SLO recovery markers and contribute to the design of strategies to mitigate SLO dysfunction in individuals accidentally or purposely exposed to gamma radiation.
In collaborative studies with Dr. Shabaana Abdul Khader, we demonstrated that the presence and organization of inducible bronchus associated lymphoid tissue (iBALT) correlates with a better control of Mycobacterium tuberculosis infection in mice, non-human primates and humans. With support from the National Institute of Allergy and Infectious Disease, we are now evaluating the cellular and molecular mechanisms implicated in the organization of the iBALT and the control of Mycobacterium tuberculosis infection. The long-term goal is to exploit the mechanisms of iBALT formation and organization for the benefit of people with active tuberculosis.
Despite the current advances in systemic lupus erythematosus, there is still an urgent need for novel therapies. Especially, therapies that target auto-reactive antibody secreting cells will be important to modulate the production of auto-antibodies and prevent immune complex mediated damage in peripheral tissues. In Dr. Jennifer Anolik’s lab and with support from Karyopharm Pharmaceutics, we are dissecting the impact of small inhibitors of nuclear export (SINE) on the generation of auto-reactive plasma cells and their influence on the pathophysiology of experimental murine lupus. The long-term goal is to selectively eliminate auto-reactive plasma cells without affecting long-lived plasma cells that are important for the protection against pathogens.
In a second project supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, we are defining the molecular signatures of inflammatory cells in the synovial tissue from patients affected by rheumatoid arthritis. The main goal is to perform laser capture of discrete cell populations, coupled to RNA sequencing (RNAseq), to define tissue, disease and cell-dependent signatures that will lead to the discovery of novel markers/targets for the diagnosis/prognosis, and treatment of rheumatoid arthritis patients.