Venkatesh Sampath, MBBS, MRCPCH

Sosland Endowed Chair in Neonatal Research; Director, Neonatal Diseases Research Program; Director, Donald Thibeault Lung and Immunology Laboratories; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Associate Professor of Pediatrics, University of Kansas School of Medicine

Full Biography

Physician-Scientist Venkatesh Sampath, MBBS, MRCPCH, Sosland Endowed Chair in Neonatology Research and Director of Neonatal Diseases Research Program, received a $2,506,606 award from the National Institutes of Health (NIH) – National Institute of Diabetes and Digestive and Kidney Diseases. The NIH award is for his project, “SIGIRR in the Neonatal Intestine.” The award runs from February 2025 through November 2028 (Project Number: R01DK139636-01A1).

Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) is a gene that regulates inflammation in the intestine. Premature infants do not have a fully developed intestinal mucosal barrier, which is the protective lining in the intestines. The lack of this barrier puts them at risk of necrotizing enterocolitis (NEC), a devastating gastrointestinal disease with up to 25% mortality with severe disease. Infants with severe NEC have death of intestinal tissue that can spread to cause shock and cardiovascular failure. Dr. Sampath’s earlier research found that genetic mutations in SIGIRR can lead to an excessive inflammatory response in response to gut bacteria, making preterm infants more vulnerable NEC.

“Among the several diseases that can affect preterm infants, NEC is very scary as many of us have seen kids develop NEC and die within a day or two despite full medical and surgical treatment,” said Dr. Sampath.

Researchers do not fully understand how NEC is caused and some researchers believe that genetic defects in intestinal mucosal barrier function that allow bacteria to invade the intestine and the blood stream contribute to NEC. In this project, Dr. Sampath and his team will study how genetic mutations in SIGIRR disrupt intestinal barrier function using several novel intestinal models they developed.

“The significance of this research lies in revealing novel mechanisms by which genetic variants program the defective intestinal mucosal barrier in NEC,” said Dr. Sampath. “Identifying these mechanisms has the potential to lead to new treatments for premature infants with NEC.”

The project’s hypothesis is that SIGIRR promotes adherens junction assembly (proteins that promote cell-to-cell adhesion) and intestinal barrier function in the neonatal intestine by inhibiting TWIST1. TWIST1 is a gene that when activated in diseased states decreases expression of E-cadherin and other proteins that keep cells glued to each other, inhibiting bacterial invasion. Dr Sampath’s team will study these key mechanisms in non-diseased states and diseased NEC states.

Co-investigators for the project include Susana Chavez-Bueno, MD, Infectious Diseases; Hung-Wen Yeh, PhD, Health Services and Outcomes Research; Shahid Umar, PhD, University of Kansas Medical Center; and Sasirekha Ramani, PhD, Baylor College of Medicine. 

The success of this grant would not have been possible without the talent and efforts of Neonatal Diseases Research Program members Wei Yu, PhD; Aparna Venkatraman, PhD; Sherry Mabry, MS: Heather Menden, MS; Marianne Nsumu, MS; Alain Cuna, MD; Miah Ruffin, BA; and Allison Scott, RN, BSN.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.