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New York City chapter of the Crohn’s and Colitis Foundation of America (CCFA) for their annual New York City Take Steps walkathon.

NYC Take Steps Pic (480x640)The Cho lab joined efforts with the New York City chapter of the Crohn’s and Colitis Foundation of America (CCFA) for their annual New York City Take Steps walkathon.

The event brings to light the struggles and triumphs of countless individuals living with Inflammatory Bowel Disease (IBD), while raising funds to aid critical research and support patient programs. Among those individuals honored at the walkathon for their significant contributions towards IBD research included Mount Sinai’s very own Dr. James Marion and his patient Amy Lane.

(Read more about their stories here: Click Here

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Upcoming Events

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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.

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Genetics of Inflammatory Bowel Disease (IBD)

CCFA Brooklyn Take Steps

October 11, 2015

2015_Brooklyn_walk_michael_yorkes_0544-LThe “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.

 

 

 

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New paper from the Cho lab published this month in Human Molecular Genetics!

Shikha Nayar present in Work in Progress (WIP) for Genetic and Genomic Sciences at Sinai
Date: 3/21/2018

Using single cell RNA sequencing to understand host-pathogen interaction of Crohn’s disease in a zebrafish model.

Ling-shiang (Felix) Chuang presented at ASCB/EMBO Minisymposium: Bactrerail Infection and Symbiosis on December 2-6 2017

Shikha Nayar and Ling-shiang (Felix) Chuang from Cho lab presented posters at American Society for Cell Biology (ASCB/EMBO) on December 2-6 2017

Single cell RNA sequencing of zebrafish intestines reveals enhanced inflammatory signatures in chemically‐induced intestinal

Zebrafish modeling defines complex innate immune mechanisms in sepsis and repetitive intestinal

Congratulations to Cho Lab members (past and present) for the publication of “Improved integrative framework combining association data with gene expression features to prioritize Crohn’s disease genes.”

One of the greatest challenges in Crohn’s disease (CD) research today is making sense of the 100+ loci from genome-wide association studies (GWAS) that increase patient risk for this multifactorial disease. Some of the known risk loci span multiple genes, and others appear to be gene deserts. In order to improve available therapies for this disease, we need to refine and prioritize the most probable candidate genes in each locus in order to properly target and treat CD. 

By integrating known associations with gene expression features such as tissue specificity, regulatory variants and differential expression in patients and healthy controls, we show that an integrative model outperforms GWAS alone in ranking the evidence for a gene being involved in CD.  Moreover, this refined set of genes is more likely to be differentially expressed in polarized proinflammatory macrophages (M1), suggesting that host control of inflammation is central to the pathology of this disease.

As research into the genetics of CD expands, the list of associated loci will follow suit. Incorporating models that include more information than genotype alone will be crucial to understanding which genes in each locus are likely contributing to this disease and how they change under certain conditions to result in disease. By collecting biological specimens from multiple sources, including intestinal biopsies and peripheral blood samples, and combining this data with results published by other groups, we can significantly expand the types of analyses performed and improve our understanding of Crohn’s disease.

Citation

Kaida Ning, Kyle Gettler, Wei Zhang, Sok Meng Ng, B. Monica Bowen, Jeffrey Hyams, Michael C. Stephens, Subra Kugathasan, Lee A. Denson, Eric E. Schadt, Gabriel E. Hoffman and Judy H. Cho.  Improved integrative framework combining association data with gene expression features to prioritize Crohn’s disease genes. Hum Mol Genet (2015). doi:10.1093/hmg/ddv142

 

 By B. Monica Bowen

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Dr. Cho attends the first annual Mount Sinai-Oxford Meeting

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.

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Dr. Judy Cho Presents at New York Genome Center

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.

 

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Dr. Judy Cho Wins CCFA Award for IBD Research

Judy Cho, MD won the prestigious Scientific Achievement in Basic IBD Research award at the annual meeting of the Crohn’s and Colitis Foundation of America (CCFA) in December, 2014. She is pictured above between Mount Sinai gastroenterologists Jean-Frédéric Colombel, MD (on the right) and David Sachar (on the left), who won the Scientific Achievement in IBD Clinical Research Award and Lifetime Achievement Award, respectively, marking the first occasion that all three CCFA awards were given to individuals of the same institution.

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2014 Updates

Happy New Year!  2014 was a highly collaborative year for the Cho Lab. Let’s take a look back at our lab’s accomplishments in 2014…

 

The Ashkenazi Genome Consortium (September 2014)

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).

The microbiome in inflammatory bowel disease (August 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).

 Functional characterization of CD risk alleles in dendritic cells (May 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).

Leveraging network analysis for inflammatory bowel disease gene prioritization (May 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).

 

by B. Monica Bowen, Cho Lab graduate student researcher