The research projects in Dr. Helmrath's lab rely on funding from the following sources:
Intestinal Organoids as a model system for studying enteric disease. Co-Investigator (PI: Brian D. Weiss, MD). NIH/NIAID 1U19AI116491-01. 03/01/15 - 02/29/20.
Mechanisms of Intestinal Stem Cell Expansion Following Resection. Principal Investigator. NIH/NIDDK R01 DK083325. 07/01/09-06/30/15.
Surgical loss of the intestine due to injury or disease may result in the inability to absorb enough liquid and food to survive. Fortunately, the remaining intestine is often able to compensate for this intestinal loss over time. When it cannot, people must receive both fluids and nutrition intravenously. Research outlined in this proposal will help us better understand how the cells that continually renew the lining of the intestine every day (intestinal stem cells) increase in number to help compensate following intestinal loss.
Investigation of Regional Identity in Human Intestinal Stem Cells. Principal Investigator. NIH/NIDDK U01 DK103117. 09/01/14-8/31/19.
The proposed work utilizes cutting edge technology to characterize the network of molecular determinants of regionalized intestinal stem cells. This work will lead to a deeper understanding of regional influence within intestinal stem cell populations that may contribute to physiological and disease specific difference commonly seen between the proximal and distal intestine.
Human Endocrine Cell Development. Co-investigator (PI: James M. Wells, PhD). NIH/NIDDK R01 DK092456. 04/07/12-02/28/17.
This application outlines specific aims to:
1) Generating multiple NEUROG3 gain- and loss-of-function lines.
2) Rigorously investigating the impact of NEUROG3 levels on pancreatic and intestinal endocrine development in vitro.
3) Identifying the molecular basis explaining our hypothesis that development of pancreatic endocrine cells occurs in a NEUROG3-independent manner in humans.
4)Investigating the impact of NEUROG3 levels on the function of human beta-cells and intestinal epithelial cells in vitro and in vivo.
Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS renewal). Co-Investigator (PI: Thomas H. Inge, MD, PhD). NIH/NIDDK UM1 DK072493. 09/23/11-08/31/16.
This UM-1 grant represents renewal funding of the Teen LABS study, originally funded under U01 DK072493. The funding will enable the study to perform long-term follow up to examine multiple outcomes of bariatric surgery on a multicenter cohort of 250 adolescents. Anthropometric data, surgical data, health outcomes, surgical complications and quality are being assessed longitudinally. Together, these data and data from ancillary studies will provide invaluable information regarding the benefits and risks of bariatric surgery in adolescents.
Single Cell/RNA-Seq dissection of Human iPS cell development into intestine. Co-Investigator (PI: Steven Potter, PhD). NIH/NIDDK R01-DK098350. 09/20/13-7/31/17.
The aims of this grant use a combination of new technologies. By allowing the generation of human intestine from pluripotent stem cells (iPS), and allowing the RNA sequencing gene expression analysis of single cells, we aim to create an atlas of the gene expression programs that drive the differentiation of the distinct intestinal lineages.
Adolescent Bariatric Surgery: Weight and Psychosocial Risk in Young Adulthood. Co-investigator (PI: Margaret H. Zeller, PhD). NIH/NIDDK R01 DK080020. 03/01/08-5/31/19.
Obesity, mental health, the engagement in HIV/sexual-risk behaviors, alcohol/tobacco/drug use, as well as suicidal behaviors are significant public health priorities for adolescents and young adults. Bariatric or weight loss surgery (WLS) has become a viable treatment option for adolescents whose obesity has progressed to extreme levels (BMI>40 kg/m).
Patient Specific Enteroids from Small Intestine and Colon. Co-Investigator (PI: Anjaparavanda P. Naren, PhD). Cystic Fibrosis Foundation Naren14XXO. 07/01/14-6/30/16.
Clinically, Dr. Helmrath’s role as the director of the Intestinal Rehabilitation Program at Cincinnati Children’s provides access to all patients with intestinal failure/diseases. The development of a tissue bank from this population of patients provides a valuable resource to study human intestinal stem cells (ISC). Dr. Helmrath will collect patient samples and oversee this Core at Cincinnati Children’s.