The central theme of our research program is to understand the host response to microbial infections of humans, particularly bacterial and fungal diseases, using animal and in vitro models. We are well-recognized for research in tuberculosis, specifically for the rabbit model. In this area, one of the goals is to determine, characterize, understand and apply the molecular immunologic and metabolic determinants underlying the progression of Mycobacterium tuberculosis (Mtb) infection to active tuberculosis (TB) versus control of infection and establishment of latency (LTBI) as well as reactivation of TB upon immune suppression. Another aspect of our research involves exploring the efficacy of adjunctive immune modulation therapy as a host-directed intervention to improve current TB treatment modalities. For these studies, we have been primarily using rabbit, mouse, rat and guinea pig; each of these models recapitulates various pathophysiological aspects seen in patients with active and/or latent TB to various extents.For the first time in literature, we have identified/reported several host gene networks/pathways that contribute to the differential outcome of Mtb infection. We have established proof-of-concept for the beneneficial effect of host directed therapy with a small molecule phosphodiesterase-4 inhibitor (PDE4i) in combination with anti-TB drugs; at present, this molecule is in human clinical trial.
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Areas Of Interest
Mycobacterial Pathogenesis and Immunity
Selvakumar Subbian, Ph.D., Associate Professor of Medicine at the Public Health
Research Institute Center of the New Jersey Medical School, Rutgers Biomedical and
Health Sciences (RBHS) at Rutgers University. Dr. Subbian?s expertise encompasses
studies of human disease and animal models to better understand host-pathogen
interactions and the role of regulation of host immune molecules in the pathogenesis
of mycobacterial infections. For the past several years, Dr. Subbian has been
studying the role of innate and adaptive immunity, particularly macrophage activation
in the host response to mycobacterial infections. More recently, Dr. Subbian and
colleagues determined that the production of macrophage pro-inflammatory cytokines
are differentially induced following infection with different clinical isolates of
Mycobacterium tuberculosis, leading to different extents of disease progression and
clinical outcome. Dr. Subbian and his team have shown that treatment with immune-
modulating thalidomide analogs modifies TNF-alpha production and can improve outcome
of standard TB therapy, in animal models (mice and rabbits) of pulmonary TB. In these
animal models, co-treatment with these analogues, in combination with antibiotics,
is significantly more efficient in reducing bacillary load and improving disease
pathology of mice and rabbits with pulmonary TB than antibiotic treatment alone. In
addition to Dr. Subbian's studies at the Public Health Research Institute, he has
collaborative studies being conducted at the Johns Hopkins University (JHU),
Baltimore and Cornell University (CU), New York. The global host gene expression
changes during pathogenic process that occurs in the Mtb-infected rabbit lungs is
being analyzed using bioinformatics approach in collaboration with Drs. Joel Bader
and Petros Karakousis at the JHU. One of the most important achievement of Dr.
Subbian is the establishment of microarray based bioinformatics approach to
understand the host factors (genes, networks and pathways) impacted by Mycobacterium
tuberculosis infection of rabbit lungs. This is the first report in the published
literature on the application of rabbit genomics to understand the pathogenesis of
active and latent tuberculosis. Dr. Subbian is extensively trained in bioinformatics
data mining and he is certified by Ingenuity Pathway Analysis (IPA) as a data
analyst. Dr. Subbian, in collaboration with Dr. Bader and his team, have contributed
significantly to improve and update the rabbit gene annotations for gene expression
studies. Dr. Subbian has recently begun a study to explore the immunemodulatory
potential of anti-TB and other therapeutic drugs used in human diseases.
