Pilot/Feasibility Program

The overall objectives of this program are to provide support for the purposes of testing innovative hypotheses which may have significant impact on digestive diseases research. Our hope is that the investigator can then develop enough preliminary data sufficient for funding of a research grant application by conventional mechanisms (e.g. R01). This program hopes to encourage young investigators and more established investigators in other field to approach problems which are relevant to our understanding of normal intestinal, liver and pancreatic function and to digestive diseases. We are particularly interested in projects that address issues in mucosal immunity, epithelial injury/repair, microbial interactions with intestinal, hepatic and pancreatic tissues. We would like to encourage efforts addressing intestinal motility and the application of novel genetic models (e.g. C. elegans, Drosophilia, etc) to address questions in GI tract development.

For questions concerning the relevance of potential applications, contact Jason Mills, MD, PhD, Director, Pilot/Feasibility Program, at jmills@wustl.edu.

The primary objective of this program is to identify projects that will:

  • Lead to further extramural, preferably NIH-funded, research support
  • Utilize one of the four Core facilities

Who is eligible?

Full time faculty and senior post-doctoral fellows at Washington University including:

  • Junior investigators without independent grant support (excluding career development awards) seeking to establish independence in digestive disease research.
  • Investigators with independent grant support (past or present) unrelated to digestive diseases-related research, now wishing to enter the field of digestive disease research.
  • Investigators with independent grant support who have previously worked in this field but wish to pursue a new research direction in the area of digestive diseases.

It is strongly suggested that you contact Dr. Mills at jmills@wustl.edu to discuss eligibility and relevance prior to submitting an application.

Application process

2020-2021 DDRCC PF Call for Applications

List of Current Awardees (2019-2020)

First Year Awardees

James White, PhD, Instructor in Medicine
Division of Infectious Diseases, Washington University School of Medicine
Title of project: Role of host immunity and microbiota in flavivirus-induced gastrointestinal dysmotility

(8/1/19 – 4/30/20)
Dr. White is an Instructor in Medicine in the Department of Medicine, Division of Infectious Diseases. His funded project will investigate the role of anti-viral CD8+ T cell responses and the intestinal microbiota in the development and persistence of GI motility disorders.

Spencer Willet, PhD, Post-Doctoral Research Associate
Division of Gastroenterology, Washington University School of Medicine
Title of project: The Role of the Hippo Pathway in Gastric Homeostasis and Metaplasia

(8/1/19 – 4/30/20)
Dr. Willet is a Post-Doctoral Research Associate in the Department of Medicine, Division of Gastroenterology. His research project and training plan will focus on bioinformatics/biostatistics (for scRNA-seq, RNA-seq, and ChIP-seq), organoid culture, Helicobacter pylori infection, and High-content imaging. The studies proposed in his application will explore how gastric cell identity is controlled and perturbed in injury and disease.

Brigida Rusconi, PhD, Instructor in Pediatrics
Pediatrics—Gastroenterology, Washington University School of Medicine
Title of project: The Role of Sphingolipid Signaling in Early Life Mucosal Immune Establishment

(8/1/19 – 4/30/20)
Dr. Rusconi is an Instructor in Pediatrics in the Department of Pediatrics, Division of Gastroenterology. Her funded project will seek to fill the knowledge gap regarding early life mucosal immune development and dysbiosis by addressing the relevance of sphingolipids, mainly sphingosine-1-phosphate, in directing this intricate relationship.

Kim Liss, MD, Instructor in Pediatrics
Pediatrics—Gastroenterology, Washington University School of Medicine
Title of project: The role of necroptosis in hepatic ischemia reperfusion injury in the setting of steatosis

(8/1/19 – 4/30/20)
Dr. Liss is an Instructor in Pediatrics in the Department of Pediatrics, Division of Gastroenterology. Her funded project will investigate the role of necroptosis in hepatic ischemia reperfusion injury to enhance our understanding of liver injury and repair, advance knowledge in clinical hepatology, and, ideally, increase donor organ availability.

Second year Awardees

Jeff Brown, MD, PhD, Instructor in Medicine
Division of Gastroenterology, Washington University School of Medicine
Title of project: CEACAMs in Metaplasia and Oncogenesis
(5/01/18 – 4/30/20)
Dr. Brown is an Instructor in Medicine in the Department of Medicine, Division of Gastroenterology. His funded project will reveal and characterize cathartocytosis, a novel cellular process, required for metaplasia and oncogenesis in several tissues and demonstrate that assaying for this process is both a sensitive and specific tool for identifying premalignant and malignant cellular transformation throughout the GI tract.

Michael Thompson, MD, PhD, Instructor in Pediatrics
Pediatrics – Endocrinology, Washington University School of Medicine
Title of project: Impact of Maternal Obesity on Bile Acid Homeostasis and Risk for Liver Fibrosis in Offspring
(5/01/18 – 4/30/20)
Dr. Thompson is an Instructor in Pediatrics in the Department of Pediatrics, Endocrinology. His funded project will characterize bile acid metabolism in mouse offspring exposed to maternal high fat/high sugar diet before and after exposure to fatty liver disease inducing diets. Once a mechanistic link is proven between altered bile acid metabolism after maternal HF/HS diet exposure and risk for NAFLD progression, this information will be used to design bile acid based preventative therapies to prevent disease progression in those patients who are at risk.

List of Previous Awardees 

Megan Baldridge, MD, PhD, Assistant Professor
Division of Infectious Diseases, Washington University School of Medicine
Title of project: Regional regulation of enteric virus infection by the commensal microbiome
(5/01/17 – 4/30/19)
Dr. Baldridge is an Assistant Professor in the Department of Medicine, Division of Infectious Diseases. Her funded project will further uncover the interactions between the microbiome, virus, and the host in different regions of the intestine. She will determine the effects of the microbiome on regional cellular viral tropism throughout the intestine using viral quantification and immunofluorescence assays and define the specific bacteria associated with murine norovirus infection in different regions of the gut using laser capture microdissection followed by next-generation sequencing to identify bacterial taxa. Her studies will make use of newly-developed techniques to explore these questions from novel angles and pursuit of these aims will also facilitate development of new methods and technical expertise.

Jaebok Choi, PhD, Assistant Professor
Division of Oncology, Washington University School of Medicine
Title of project: Effect of JAK1/JAK2 Inhibition on Intestinal Stem Cells and Tissue Repair
(5/01/17 – 4/30/19)
Dr. Choi is an Assistant Professor in the Division of Oncology.  His funded project will determine the effect of baricitinib on ILCs using flow cytometry and Paneth cells and ISCs in the GI tract using immunofluorescence microscopy.  Most patients receiving allo-HSCT suffer from GI GvHD, the major complication of allo-HSCT, due to human leukocyte antigen (HLA) mismatch. Dr. Choi’s work will provide mechanistic insights into not only GI GvHD, but also other chronic inflammatory diseases such as IBD, Crohn’s disease and ulcerative colitis. His study’s goal is to provide an inexpensive, safe and effective way of overcoming these diseases.

Vincenza Cifarelli, PhD, Assistant Professor
Division of Nutritional Science, Washington University School of Medicine
Title of project: CD36 regulation of gut lymphatics
(5/01/18 – 4/30/19)
Dr. Cifarelli is an Assistant Professor of Medicine in the Department of Medicine, Division of Nutritional Science. Her funded project will seek to better understand intestinal lymphatic system during lipid absorption. She will identify a novel regulation of lacteal maintenance and function mediated by the lipid translocase CD36. She will propose that CD36 promotes proteolytic maturation of vascular endothelial growth factor C, VEGF-C, during lipid absorption. She expects to dissect the molecular mechanisms that regulate proteolytic maturation and secretion of VEGF-C during lipid absorption. Her project’s hypothesis is that that lipid absorption induces, via CD36, secretion and maturation of VEGF-C, to help prime the lacteals for chylomicron uptake and lipid transport. She will hypothesize that CD36 mediates regulation of lacteal regeneration and function during the fasting/refeeding conditions.

Kyle McCommis, PhD, Assistant Professor
Division of Geriatrics and Nutritional Science, Washington University School of Medicine
Title of project: Inhibiting pyruvate metabolism to treat hepatic fibrosis
(5/01/18 – 4/30/19)
Dr. McCommis is an Assistant Professor in Medicine in the Department of Medicine, Division of Geriatrics and nutritional Science. His funded project will investigate the importance of a metabolic process in the regulation of fibrosis development in fatty liver disease. As the amount of fibrosis is the best indicator of morbidity and mortality from fatty liver disease, understanding how to limit or reverse liver fibrosis would be key to improving health from this highly common disease.

Megan Cooper, MD, PhD, Assistant Professor
Department of Pediatrics Rheumatology, Washington University School of Medicine
Title of project: Intestinal epithelial cell turnover in a murine model of STAT3 gain-of-function
(5/01/17 – 4/30/18)
Dr. Cooper is an Assistant Professor in the Department of Pediatrics, Division of Rheumatology. Her funded project will study a group of patients with genetic abnormalities in STAT3 that causes increased STAT3 function and leads to early-onset autoimmune disease. Most of these patients suffer from gastrointestinal disease including inflammation of the intestines and liver. To further investigate how mutations in STAT3 lead to a human disease, her laboratory generated two mouse models with mutations in the murine Stat3 gene corresponding to those found in patients. Preliminary evaluation of the gastrointestinal tract of these mice suggests that they have abnormalities of their small intestines with increased proliferation of epithelial cells. Her work hypothesizes that increased STAT3 function leads to a phenotype similar to that seen with viral infection and type I interferon signaling with increased epithelial cell turnover and that this is a precursor to inflammation of the intestines. The aims of this project are to: 1) Investigate epithelial cell proliferation in a larger group of mice with Stat3 mutations, and 2) Determine if viral infection alters epithelial cell proliferation in mice with Stat3 mutations and induces enteritis. Dr. Cooper will use in vivo mouse models to complete these studies. This anticipate that this project will provide insight into the mechanisms whereby increased STAT3 function causes inflammation of the intestines and liver in patients.

Samantha Morris, PhD, Assistant Professor
Department of Developmental Biology and Genetics, Washington University School of Medicine
Title of project: Single-cell RNA-seq mapping of an in vitro intestinal regeneration model
(5/01/17 – 4/30/18)
Dr. Morris is an Assistant Professor in the Department of Developmental Biology and Genetics. Her funded project will study the overarching hypothesis that in vitro intestinal organoid models can recapitulate the in vivo microenvironmental cues to fully differentiate iEPs to mature, functional intestine. The innovation of this project is that we will establish a tractable platform to enable the precise charting of intestinal differentiation from an induced progenitor state, with single-cell resolution. This will pave the way for generating an array of gastrointestinal cells for therapy, and in vitro disease modeling.

Guoyan Zhao, PhD, Assistant Professor
Department of Pathology & Immunology, Washington University School of Medicine
Title of project: Characterization of a Novel Gene Associated with Inflammatory Bowel Disease
(5/01/17 – 4/30/18)
Dr. Zhao is an Assistant Professor in the Department of Pathology & Immunology. Her funded project will study the function of IRNG (IBD-related novel gene) and if it is involved in IBD pathogenesis.  From preliminary findings, Dr. Zhao hypothesizes that IRNG encodes a secreted protein and functions as a cytokine. The specific aims are: Specific Aim I: Determine IRNG gene expression in different human tissues and in tissues from IBD patients by computational analysis of published RNA-Seq data. Specific Aim II: Test the hypothesis that IRNG encodes a secreted protein. Specific Aim III: Identify cell-intrinsic function of IRNG by comparing gene expression profiles between wild-type cells and Caco-2 cells lack IRNG function with and without virus infection using RNA-seq.  The overall goal is that if IRNG is involved in IBD pathogenesis, it would offer a potential novel target for IBD treatment.

Kathryn Knoop, PhD, Instructor in Medicine
Division of Gastroenterology, Washington University School of Medicine
Title of Project: Gut Mechanism of Neonatal Sepsis
(5/01/15 – 4/30/17)
Dr. Knoop is a Postdoctoral Research Scholar in the Division of Gastroenterology. Her funded project will study will evaluate if the resident gut bacteria transverses the neonatal intestinal epithelium via GAPs and whether this occurs as part of the normal developmental process or whether this results due to loss of factors in the maternal breast milk that normally inhibit GAP formation. Aim 1 will develop a model for LOS and evaluate if maternal factors in the breast milk inhibit bacterial translocation and sepsis by inhibiting GAP formation, and evaluate if replacing the missing maternal factors can prevent sepsis as a potential therapy for LOS. Aim 2 will evaluate the differences in the immune response after infection with pathogens between neonates and infants to better understand why infants are protected from disease despite presence of bacteria in the organs. Completion of these studies will result in understanding how bacterial strains causing LOS cross the intestinal epithelium and what ages are most susceptible to bacterial translocation. By evaluating if supplementation with maternal factors can prevent sepsis, a potential therapy will have been discovered.

Blair Madison, PhD, Assistant Professor
Division of Gastroenterology, Washington University School of Medicine
Title of Project: Dissecting the Combinatorial Roles of Let-7 Target mRNAs in Colorectal Cancer
(5/01/15 – 4/30/17)
Dr. Madison is an Assistant Professor in the Division of Gastroenterology. His funded project will study the role of Let-7 targets in colorectal tumorigenesis. Using mouse models to manipulate Let-7 levels specifically in the intestine epithelium, he has revealed a critical role for tumor suppression by this miRNA family. However, one of the most arduous task of many miRNA studies is determining the relevant targets that are responsible for a given phenotype. Dr. Madison has identified 8 highly up-regulated Let-7 target mRNAs, including suspected proto-oncogenes HMGA2, IGF2BP1, IGF2BP2, and MYCN, along with several transcription factors: PLAGL2, ARID3A, E2F5, and HIF3A. Although these factors likely operate independently, it was found that several of these targets converge on the pro-oncogenic IGF2/miR-483 locus. The goal of this Pilot and Feasibility project is to examine how these targets cooperatively augment intestinal tumorigenesis, with the hypothesis that activation of the IGF2/miR-483 locus is triggered following loss of Let-7 miRNAs. In addition to in vitro cell culture models (enteroids) for investigating cooperation between these targets, Dr. Madison will test the feasibility of a novel conditional transgenic mouse model using a mutant Piggybac transposase.