ACS Award Helps Pioneer Treatment for Congenital Colorectal Disease

The recipient of the 2015–2020 George H. A. Clowes Jr., MD, FACS, Memorial Research Career Development Award—Ankush Gosain, MD, PhD, MBA, FACS—often begins his presentations on the treatment of infants born with Hirschsprung disease by referencing the iconic children’s book Everyone Poops by Taro Gomi.

“In the book, there’s a boy who doesn’t want to potty train, and the parents are telling him that everyone poops,” explained Dr. Gosain, surgeon-in-chief at the University of Virginia (UVA) Health Children’s Hospital in Charlottesville and the C. Bruce Morton Professor of Surgery and chief of the UVA Division of Pediatric Surgery. “But that’s actually not true. Babies who are born with Hirschsprung disease—a disorder of the enteric nervous system also known as the brain of our gut—can’t poop.”

Dr. Gosain is a pediatric surgeon-scientist whose research, which aims to bridge basic and translational science, focuses on the enteric nervous system and gastrointestinal mucosal immune development, particularly in relation to congenital colorectal diseases like Hirschsprung disease.

With Hirschsprung disease, the infant is born without ganglion cells in part of their colon, causing a functional blockage that prevents normal stool passage, leading to severe constipation and bowel obstruction. The treatment for this condition is surgery to remove the aganglionic bowel segment.

“When I was nearing the end of my pediatric surgery fellowship, I was taking care of babies with Hirschsprung disease,” said Dr. Gosain. “One of the problems with this congenital condition is it can have a dramatic presentation. They come in with a life-threatening complication called Hirschsprung-associated enterocolitis (HAEC), where their bellies are big and distended, and they’re vomiting, have diarrhea, and are on death’s door. If you don’t make the correct diagnosis, it has the potential to go the wrong way.”

HAEC impacts 30%-60% of infants with the disease and is the leading cause of death among these patients.

Dr. Gosain received the Clowes Award for his pioneering work studying the enteric nervous system and gastrointestinal mucosal immune development and function as they relate to congenital colorectal disease, specifically Hirschsprung disease.

“Getting the Clowes Award was a truly memorable time in my career,” said Dr. Gosain, an ACS Fellow since 2012. “I think anytime you receive an award from the ACS, it is a major stamp of approval and an affirmation that the work you’re doing has an important impact on our patients and our profession.”

The Clowes Award—which is supported through contributions to the ACS Foundation with funding from The Clowes Fund, Inc.—is intended to support the research of a promising young surgical investigator and offers a stipend of $45,000 for each of 5 years.

Dr. Gosain learned he would be receiving the Clowes Award in spring 2015, after being recruited to The University of Tennessee Health Science Center in Memphis, as an associate professor of surgery and pediatrics.

“The Clowes Award came at a time when my startup funds were starting to dwindle, and it really provided extra support that was necessary to keep a lot of my work going,” he said, noting that such supplemental funding can help cover salary gaps that can result from receiving a National Institutes of Health (NIH) grant, which mandates a statutory salary limit.

According to Dr. Gosain, the difference between the actual salary and the capped amount is typically absorbed by the institution, often via departmental cost-sharing. “NIH funding is unsustainable for most academic departments of surgery, so having additional sources of funding from nonfederal sources like the ACS helps surgeon-scientists pursue their work.”

For Dr. Gosain, this work focused on exploring offshoots of research data outside the scope of the NIH grant that led to newer or tangential lines of investigation, culminating in his first Research Project Grant in April 2020, commonly known as an R01 grant, of more than $2 million for his project “Dysbiosis in Hirschsprung-Associated Enterocolitis Pathogenesis.”¹

Specifically, the aim of this research project was to determine a causative relationship between dysbiosis and HAEC and identify which bacteria lead to the development of HAEC.

“We would operate on these children, and they would get better, but then they’d come back after surgery with the same problem happening over and over again—as if we hadn’t done the right operation for them,” explained Dr. Gosain. “This got me thinking that, for this disease process, there must be some kind of interaction happening in the gut. We have this brain of the gut, the enteric nerve system, and maybe that system is ‘talking’ with the gut mucosal immune system and influencing how it functions. I decided I was going to tackle this problem because it was really frustrating to me as a surgeon, not to mention to the patients and their families.”

Using a mouse model, Dr. Gosain conducted a fecal microbiota transplant to confirm that overall decreased diversity of bacteria in the gut can drive the development of Hirschsprung-associated enterocolitis.

“The grant that we had been awarded previously allowed us to focus on the mucosal immune system and lymphocytes B cells in particular. What we were finding was that our mice and the immune system findings weren’t enough to explain why these patients were getting sick,” he said. “At the time, the field of research into the microbiome was just starting to skyrocket—and we quickly realized that these microbiome studies were costly. Funding from the Clowes Award helped support some of that work and helped us define that, yes, this is a major part of how this disease develops and progresses. That finding then became the focus of that first R01 regarding how the microbiome impacts the pathogenesis of HAEC.”

Dr. Gosain’s lab, founded in 2010, is the only NIH-funded lab in the country to specifically study HAEC.¹

“We had always thought about Hirschsprung disease as a black-or-white disease—that you have the enteric nervous system in part of the gut, and you don’t have it in this other part of the gut. If you take out that part of the gut that doesn’t have the enteric nervous system—all the problems should be solved. The clinical findings show that’s not the case,” he said. “These children continue to struggle, at least half of them do. We thought maybe the enteric nervous system that is present isn’t normal. Our lab was the first to define that in mice—and then our group and others—defined that as well in patients via their resection samples from their surgeries.”

In 2021, Dr. Gosain and colleagues published a paper in Pediatric Surgery International, “Resection Margin Histology May Predict Intermediate-Term Outcomes in Children with Rectosigmoid Hirschsprung Disease.”² The study, which cites funding from the Clowes Award, NIH, and other sources, examined patient pathology specimens as well as the results of quality-of-life surveys administered to children and their families 3 to 5 years after surgery.

“We found that the more abnormal the histology was, the poorer the quality of life was for the child, which changed how we counsel patients and families about what to expect after surgery,” Dr. Gosain said. “It also opened up this new area that’s a potential target for therapy, which has become a lot of the work the Gosain Lab is doing now—namely, how do we augment the function of the enteric nerve system and immunity in those kids who have had their surgeries already?”

ACS Traveling Fellowship to Germany

As the 2019 recipient of the ACS Traveling Fellowship to Germany, Dr. Gosain was provided with the opportunity to attend the German Society of Surgery annual conference in Munich, which is a forum for interdisciplinary exchange of research and best practices. He also attended a meeting of the ACS Germany Chapter and visited medical centers in Berlin, Mainz, and other cities.

The ACS International Relations Committee selects an ACS Fellow for this opportunity, which awards $10,000 (US dollars) to cover travel, lodging, and other expenses.

“The ACS Traveling Fellowship to Germany helped grow my professional network outside of the US,” explained Dr. Gosain. “During that time, and after the fellowship ended, I had the opportunity to speak with a lot of pediatric surgeons about the challenges we were facing. Many of them were not basic or transformational scientists like myself—but we were all talking about the fundamental clinical diagnostic dilemmas we encounter with this disease.”

These discussions eventually led to the formation of collaborative work groups with the goal of publishing guidelines outlining how pediatric surgeons should approach Hirschsprung disease surgically. These findings were published in the Journal of Pediatric Surgery in 2019, with additional findings published in subsequent issues of the journal.³ 

The 2019 guidelines described standardized principles for surgical and pathology reporting to improve outcomes for Hirschsprung disease patients and “facilitate identification of correlations among morphology, function, genetics and outcomes, which are required to improve the overall management of these patients.”

In 2024, Dr. Gosain and colleagues published another article in the journal outlining recommendations for managing children with total colonic Hirschsprung disease before and after reconstruction, including “diagnostic criteria, surgical approaches, bowel management, diet, antibiotic prophylaxis, colonic irrigations, and post-surgical considerations.”⁴

Navigating Dual Career of Surgeon-Scientist

Integrating clinical practice and training with dedicated time for research can be a daunting task for surgeon-scientists, particularly for younger investigators.

In the 2019 article “A Roadmap for Aspiring Surgeon-Scientists in Today’s Healthcare Environment,” cowritten by Dr. Gosain and published in the Annals of Surgery, the authors provided a suggested timeline for the next generation of surgeon-scientists to establish a career and identify mentors.⁵ For example, years 2 to 3 are opportune times to begin writing grants and pursuing extramural research funding, as the first year is typically devoted to obtaining a faculty position and determining an area of preferred research focus.

“There is a roadmap to follow. You can look at people who are 5 to 10 years down the road from where you are currently and see that the path they followed has been successful for them,” said Dr. Gosain. “All of this assumes that you are genuinely passionate about the science itself, that you want to make a contribution, and that it’s the thing that gets you out of bed every single day. You need that mindset.”

Selecting an institution where the surgeon–scientist is a strategic priority, supported by mentors with a demonstrated history of delivering results also is essential.

“I think that surgeon-scientists live in this strange world where faculty who are 100% research focused don’t understand what we do when we’re not in the lab. And faculty who are 100% clinical don’t understand what we do when we’re not in clinic or in the OR,” Dr. Gosain said. “As surgeon-scientists, it’s our job to link these two worlds and make sure each understands the importance of the other, as we help translate the work back and forth. As surgeons, we have access to patients and tissue and blood samples and stool samples that no other specialty really has. I think being able to capitalize on that access and bring those things into your lab and use them to advance the work is critically important. That is my pitch for being a surgeon-scientist.”

To learn about the basic requirements and obligations associated with the Clowes Award, visit facs.org/clowes.

For more information about the ACS Foundation, the programs it supports, and how to contribute, check out facs.org/foundation.

Tony Peregrin is the Managing Editor of Special Projects in the ACS Division of Integrated Communications in Chicago, IL.

References

1. Le Bonheur Children’s Hospital. Researchers receive NIH R01 Awards: Ankush Gosain, MD, PHD. Fall 2020. Available at: https://www.lebonheur.org/publications/delivering-on-a-promise/research-launchpad/researchers-receive-nih-r01-awards-ankush-gosain-md-phd. Accessed January 7, 2026. 
2. Brooks LA, Fowler KL, Veras LV, Fu M, Gosain A. Resection margin histology may predict intermediate-term outcomes in children with rectosigmoid Hirschsprung disease. Pediatr Surg Int. 2020;36(8):875-882.
3. Veras LV, Arnold M, Avansino JR, Bove K, et al; American Pediatric Surgical Association Hirschsprung Disease Interest Group. Guidelines for synoptic reporting of surgery and pathology in Hirschsprung disease. J Pediatr Surg. 2019;54(10):2017-2023.
4. Rentea RM, Bokova E, Frischer JS, Gosain A, et al; American Pediatric Surgical Association Hirschsprung Disease Interest Group. Evaluation and management of total colonic hirschsprung disease: A comprehensive review from the American Pediatric Surgical Association Hirschsprung Disease Interest Group. J Pediatr Surg. 2024;59(11):161677.
5. Goldstein AM, Blair AB, Keswani SG, Gosain A, et al; Basic Science Committee of the Society of University Surgeons. A roadmap for aspiring surgeon-scientists in today’s healthcare environment. Ann Surg. 2019;269(1):66-72.