Thursday, April 7, 2106 – Faculty Poster Presentations
Wine and Hors d’Oeuvres Reception, House of the Redeemer
http://www.houseoftheredeemer.org/
Re-Shaping the thinking of IBD:
Investigating rare genetic variations in the pro-and anti-inflammatory balance between innate immunity, intestinal epithelia and gut microbiota.
A major focus of our research is understanding the prevalence of IBD in the Ashkenazi Jewish population. We are working on further identifying rare disease associated variants in Ashkenazi Jewish population by Exome Chip technology as well as the biological function of those identified genes. Dr. Cho’s research has contributed to defining the pathophysiologic mechanisms of IBD by identifying associations to NOD2, IL23R, and 163 loci to IBD. With new findings our research is evolving to now looking at the function of lipid mediators and their related cytokines in innate immune cells, and the full transcriptome of enteroids, the intestinal epithelial stem cells.
Furthermore, we investigate the relationship between environmental factors and IBD by examining how hosts (humans) interact with gut microbes and how the interaction may lead to IBD susceptibility and/or maintain IBD pathogenesis. By dissecting the relationship between IBD genetics, immune response, and microbes, we would have a better chance to develop treatment for blocking pro-inflammatory proteins, inflammatory pathways, or immune cell entry into intestine. The integration of our research with the clinical research for IBD has great potential for the future of IBD treatment.
CCFA Brooklyn Take Steps
October 11, 2015
The “Take-Steps “ is a bold and noble endeavor that the Crohn’s & Colitis Foundation of America (CCFA) embark on each year, pooling together its centers around the nation to facilitate their largest fundraising event.
The event raises awareness on the struggles and celebrates the triumphs of more than 1.4 million Americans that are ailing from inflammatory bowel disease (IBD), namely, Crohn’s disease and ulcerative colitis. The funds that are raised go towards helping facilitate educational and outreach campaigns, supports patient care programs and drives crucial research studies, which are focused on elucidating more information on the disease.
This year, the Genetics of IBD research team from The Icahn School of Medicine at Mount Sinai, led by Drs. Judy Cho and Inga Peter, joined the efforts of CCFA at the Brooklyn Take Steps event and helped raise awareness on the struggles and triumphs of many IBD patients, as well as aided to promote efforts towards IBD research.
Initiated by Dr. Judy Cho’s efforts to collaborate with her peers in Oxford, UK, the first annual meeting among the faculty of Mount Sinai and those of Oxford University occurred on Feb 23rd-24th of 2015. The Mount Sinai attendees included those of a few departments who collaborate among each other in biomedical research. A wide array of research topics such as IBD clinical and translational research, human immune monitoring and new technology, immuno-oncology, and microbiome and genetics were discussed at the symposium. Dr. Cho presented on the “Common and rare variation in inflammatory bowel disease (IBD),” and the meeting concluded with a planning discussion of the next steps for the research topics discussed.
On February 4th, 2015, Judy Cho, M.D. discussed IBD in Ashkenazi Jewish populations in a presentation titled “Common and rare variation in inflammatory bowel disease (IBD): studies in Ashkenazi Jewish populations” at the Five Point Lecture Series of New York Genome Center. Dr. Cho expounded on the evolution of the Ashkenazi Jewish susceptibility to IBD and what the future holds for identifying the genetic markers of this susceptibility. She hypothesized that that the rare genetic variation predominantly observed in Jewish populations will provide key pathophysiologic insight for IBD.
The Five Points Lecture Series, held every week, brings both local and distant scientists to discuss their work in technical detail. The speakers offer intriguing findings and thoughtful perspectives in full scientific depth. The talks, which last approximately 45 minutes, generally frame about five key points, aptly earning the title “Five Points Lecture.” More information regarding the lecture series and the New York Genome Center can be found on the center’s website.
As part of the Ashkenazi Genome Consortium, our lab contributed to the sequencing and analysis of 128 Ashkenazi Jewish genomes. These efforts shed light on the demography and genetic architecture of this population, and established an invaluable resource for future genetic studies, including studies of IBD.
Publication:
Carmi, S. et al. Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins. Nat Comms 5, 4835 (2014).
In collaboration with the Flavell lab, we showed that the intestinal microbiota of IBD patients, when grown in anaerobic culture and given to mice, contributes to the development of colitis in previously germ-free mice. This suggests that certain commensal bacteria may be drivers of intestinal inflammation in IBD.
Publication:
Palm. N. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. 158, 1000–1010 (2014).
In collaboration with the Abraham lab, we showed that immune cells from carriers of the ICOSLG CD risk allele have reduced PRR-induced cytokine responses, and the same risk allele is associated with an ileal Crohn’s disease phenotype. This work elucidates the relationship between ICOSLG and NOD2 and further characterizes Crohn’s disease as a disruption of immune homeostasis.
Publication:
Hedl, M. et al. Pattern recognition receptor signaling in human dendritic cells is enhanced by ICOS ligand and modulated by the Crohn’s disease ICOSLG risk allele. 40, 734–746 (2014).
Genetic studies of IBD have implicated over a hundred loci, but many remain to be discovered, and establishing the most biologically relevant genes is a real challenge. In collaboration with the Zhao lab, we explored the utility of gene expression networks in understanding the pathology of IBD. Studying how these gene networks are rewired in IBD patients compared to healthy controls has the potential to identify genes that, when disrupted, take an entire network with them. This can provide a method for ranking the contribution of known and novel genes to the disease.
Publication:
Hou, L. et al. Guilt by rewiring: gene prioritization through network rewiring in genome wide association studies. 23, 2780–2790 (2014).