Research Group Overview

The long-term goal of the Nutritional Immunology & Molecular Medicine (NIMM) Research Group Directed by Drs Bassaganya-Riera and Hontecillas is to elucidate the cellular and molecular mechanism(s) by which novel immune therapeutics modulate chronic inflammatory and infectious diseases. Our four principal lines of research are: 1) nutritional immunology, 2) gastrointestinal health, 3) obesity and its comorbidities (i.e., type 2 diabetes and cardiovascular disease) and 4) modeling immune responses. Modulation of inflammation and immunity are common integrative themes.

Center for Modeling Immunity to Enteric Pathogens (MIEP)

The MIEP is one of four NIAID-funded National Centers in Modeling Immunity for Biodefense. The MIEP is a collaborative $10.6M program Directed by Dr. Bassaganya-Riera with the mission of understanding the mechanisms of action underlying immune responses to gut pathogens. To achieve this goal MIEP will develop and disseminate new and improved computational and mathematical models of the mucosal immune system to generate new knowledge from immunology and infectious disease datasets. To engage the immunological research community, MIEP will provide a user-friendly web-based immunological experimentation environment that incorporates the models, is programmatically tied to the Immunology Database and Analyses Portal (ImmPort), and offer traning on modeling mucosal immunity.

See press release for additional details https://www.vbi.vt.edu/public_relations/press_releases/vbi_awarded_10_million_from_nih_to_model_immune_responses_to_gut_pathogens

Nutritional Immunology 

NIMM research characterized the modulatory effects of conjugated linoleic acid (CLA) on inflammation and immunity. This research was recognized by the American Society of Nutritional Sciences from which Dr. Bassaganya-Riera was awarded the 2005 Bio-Serv Award. Dr. Bassaganya-Riera was awarded US$ 263,439 by Mead Johnson Nutritionals-Bristol Myers Squibb for the project entitled "Assessment of a docosahexaenoic acid (DHA) and arachidonic acid (ARA)-enriched infant formula on immune responses in neonatal piglets." Dr. Bassaganya-Riera and colleagues found that when DHA and ARA are fed in combination (0.63/0.34%) to neonatal piglets they elicit significant immunosuppressive effects. These results raise questions about the safety of adding these two fatty acids to infant formulas.

In 2007, NIMM Research group was awarded a $1.2 million RO1 grant by the National Center for Complementary and Alternative Medicine designed to determine whether the phytohormone abscisic acid (ABA) elicits its immunomodulatory actions through peroxisome proliferator-activated receptor (PPAR) gamma-dependent or gamma-independent mechanism(s). The group has elucidated the mechanism of action underlying the immunoregulatory actions of ABA and discovered a novel class of ABA-like compounds that can be develop as therapeutics for inflammatory diseases.

Gastrointestinal health

Peroxisome proliferator-activated receptors (PPARs) are novel members of the nuclear receptor superfamily with three isoforms (alpha, gamma, and delta) that translate nutritional or pharmacologic stimuli into changes in gene expression, including a down-regulation of cytokine and chemokine expression. The two clinical manifestations of inflammatory bowel disease (IBD) -- Crohn's disease (CD) and ulcerative colitis (UC) -- afflict over 1 million people in North America and 4 million people worldwide. Current treatments against IBD have improved, but they are modestly successful for the long-term management of the disease and result in significant side effects. Dr. Bassaganya-Riera first reported the efficacy of CLA in ameliorating gut inflammation in a pig model and proposed that some of the beneficial effects of CLA on mucosal immune responses could be mediated by epithelial and immune cell PPAR gamma. Recent results fulfilled the prediction of the group's previous hypothesis, as the deletion of the PPAR gamma gene in immune and epithelial cells abrogated CLA's anti-inflammatory actions in the gut. Dr. Bassaganya-Riera and colleagues also found that PPAR gamma is required for Treg's anti-inflammatory function. Consistent with the concept from bench to bedside, Dr. Bassaganya-Riera is translating the basic scientific understanding of the role of PPAR gamma in the pathophysiology of gut inflammation into the clinic through extramurally funded research collaborations with University of North Carolina at Chapel Hill. 

Our group also led the efforts to sequence the whole genome of an Amerindian strain of H. pylori. These ongoing efforts will not be combined with MIEP.

https://www.vbi.vt.edu/public_relations/press_releases/helicobacter_pylori_genome_sequence

Type 2 diabetes and obesity

According to recent estimates from the Centers for Disease Control and Prevention, 30% of the United States population is obese and 65% is overweight. One of the major consequences of these high rates is manifested by the increased prevalence of type 2 diabetes mellitus (T2D), a chronic disease characterized by systemic insulin resistance and inflammation. In 2004, it was estimated that 20.8 million Americans had T2D and over 40.1% of middle-aged adults have prediabetes, with healthcare costs for diabetes treatment over US$ 132 billion and US$ 394 billion for treating cardiovascular disease and stroke (Center for Disease Control and Prevention). Current antidiabetic drugs elicit important insulin-sensitizing and anti-inflammatory effects, but side effects associated with using these medications are significant. Dr. Bassaganya-Riera's laboratory is actively screening and discovering novel, naturally occurring, orally active nutraceuticals against diabetes and cardiovascular disease that activate nuclear receptors. Of note is the discovery of a PPAR gamma-activating and anti-inflammatory phytohormone, abscisic acid (ABA), which is also a potent antidiabetic agent. Following an in vitro screening of its PPAR gamma agonistic activity, Dr. Bassaganya-Riera and coworkers generated molecular evidence in vivo showing that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting monocyte chemoattractant-1 (MCP-1) expression and macrophage infiltration through a PPAR gamma-dependent mechanism. They plan to use ABA as a proof-of-concept to establish a solid innovation pipeline of immune modulatory compounds for chronic disease prevention. Drs Bassaganya-Riera, Hontecillas and Guri are co-inventors in a Patent (US 7,741,367) with claims protecting the anti-diabetic actions of ABA.

The NIMM is pursuing commercilization of this class of compounds through BioTherapeutics

https://www.vbi.vt.edu/public_relations/press_releases/biotherapeutics_inc_launched

Leader: Josep Bassaganya-Riera