Intestinal Adaptation Laboratory

The Intestinal Adaptation Laboratory at St. Louis Children's Hospital seeks to understand the mechanisms through which the intestine adapts to massive intestinal loss.

Multiple human conditions exist in which a large proportion of the intestine needs to be surgically removed or is lost due to injury, inflammation or interruption of blood supply. Once the intestine is removed, the remaining bowel senses this acute loss and tries to compensate by a process termed adaptation.

This adaptive response consists of increases in cellular proliferation within the mucosa as well as a slight bit of growth in intestinal length and caliber. During this time, patients clinically require intravenous nutrition to supplement what cannot be absorbed entirely by the gastrointestinal tract.

A full adaptation response is achieved when patients are able to tolerate full feedings by mouth and no longer need supplemental intravenous nutrition. In many circumstances, the adaptation response is incomplete, and many of these patients require a lifetime of parenteral nutrition and its allied complications.

The main thrust of the Intestinal Adaptation Laboratory is to more fully understand this response and thereby be able to enhance it. Ultimately, growing the bowel back will permit patients to achieve a more normal lifestyle and avoid the complications associated with intravenous nutrition.

The laboratory is run jointly by Brad W. Warner, MD, Christopher R. Erwin, PhD, and Jun Guo, PhD. This team blends sophisticated molecular biology techniques with clinically focused relevant applications. The technology utilizes transgenic, knockout and mutant mice in a unique intestinal resection surgical model. In addition, laser capture microdissection (LCM) microscopy is used to study adaptation in isolated cells of the small intestine. 

Our specific research goals include elucidation of the role of epidermal growth factor (EGF) and its intestinal receptor (EGF-R) as a central mediator of the adaptation response. Two general themes currently are being investigated:

  • The role of EGF and its intestinal receptor in the signals for enterocyte proliferation following small bowel resection. We have found that the cyclin-dependent kinase inhibitor p21 is paradoxically required for the induction of proliferation. We are currently investigating the link between EGF receptor signaling and induction of p21 expression both in vivo and in vitro.
  • We recently have identified that not only is enterocyte proliferation increased but so, too, is enterocyte apoptosis. We therefore are investigating the link between EGF receptor signaling and attenuation of the apoptotic response of the enterocyte.
Contact Us:
Brad W. Warner, MD
Pediatric Surgeon-in-Chief
St. Louis Children's Hospital
Jessie L. Ternberg, MD PhD Distinguished Professor of Pediatric Surgery
Chief, Division of Pediatric Surgery
Washington University School of Medicine

St. Louis Children's Hospital
Suite 5560 - Campus Box 8235
One Children's Place
St. Louis, Mo 63110
(314) 454-6022
E-mail brad.warner@wustl.edu 

Christopher R. Erwin, PhD
Associate Professor of Surgery
Division of Pediatric Surgery
Washington University School of Medicine

St. Louis Children's Hospital
Suite 5560 - Campus Box 8235
One Children's Place
St. Louis, Mo 63110
(314) 454-6022
E-mail erwinc@WUSTL.EDU

Jun Guo, PhD
Assistant Professor of Surgery
Division of Pediatric Surgery
Washington University School of Medicine

St. Louis Children's Hospital
Suite 5560 - Campus Box 8235
One Children's Place
St. Louis, Mo 63110
(314) 454-6022
E-mail guoj@wudosis.wustl.edu