The Targan Laboratory and other research laboratories in the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute (IBIRI) focus primarily on the genetic and immunopathologic mechanisms of inflammatory bowel disease (IBD). Combining multiple research disciplines of IBD and translating findings for therapeutic development is a unique feature of the IBIRI laboratories under the Targan Lab umbrella.
Researchers in the Targan Lab are deploying stem cell technologies to study IBD. They have discovered technology to derive induced pluripotent stem cells from lymphoblastoid B cell lines and multiple other tissues and to direct these cells to form human intestinal organoids. The organoids are used to generate gene-specific models for the study of gut inflammation and, ultimately, to explore the potential of stem cell treatments for IBD.
In a genetically heterogeneous group of diseases like IBD, the Targan Lab and IBIRI researchers are working to understand the relationships of these genes with each other as well as with their individual or combined functional downstream consequences and effects on disease phenotype.
The Targan Lab and IBIRI research labs have developed in vivo and in vitro modeling systems to define the biologic consequences of IBD-associated genetic variations. With these techniques, they have discovered that the gene TNFSF15 and the protein it encodes, TL1A, are not only master regulators of intestinal inflammation but also play an important role in fibrosis, thus contributing to severe disease phenotypes and forms of IBD characterized by complications such as fibrostenosis.
The Targan Lab and other IBIRI labs have also shown that TL1A levels can influence regulatory cells, leading to either a proregulatory or a protective mucosal environment. Work in the IBIRI labs on TL1A has led to human testing of blocking this protein as a treatment for IBD.
The Targan Lab and IBIRI lab groups have led the effort to discover and define the relationships between a set of serum autoantibodies and IBD. The Targan Lab has found that, in addition to their utility in diagnosis, prognosis and treatment outcomes, combinations of these and other markers, along with genetic profiles, can predict disease natural history, response to treatments and potential need for surgery.
In addition, the Targan Laboratory is exploring molecular and epigenetic mechanisms to determine the roles of the mechanisms in the immunopathogenesis of IBD. The Targan Lab has found epigenetic alterations in a subgroup of patients with IBD.
With the addition of the IBD Drug Discovery and Development Unit, the IBIRI laboratories are speeding these discoveries to the development of new, highly targeted treatments for individuals with IBD.
The Targan Laboratory and IBIRI labs have been awarded numerous investigative grants from the National Institutes of Health and the Crohn's and Colitis Foundation of America, as well as research contracts with many industry sponsors.