Gastroenterology Faculty Research Activities

Mark Lowe, MD, PhD, has a longstanding interest in the mechanism behind the digestion of dietary fat. An important focus of his laboratory is defining the role of specific lipases at various ages. Through animal models, Dr. Lowe has demonstrated that a different lipase mediates dietary fat digestion in newborns compared to adults. The lab also studies the relationship between dietary fat digestion and appetite regulation. His laboratory has developed a mouse with a deficiency of procolipase, a pancreatic protein with an important role in both dietary fat digestion and appetite regulation. Finally, his laboratory has recently taken a new direction to understand the pathophysiology of pancreatitis and indomethacin-induced gastric injury. These studies center on a newly described protein, integral transmembrane protein 1 (Itmap1). Using a mouse model of Itmap1 deficiency, Dr. Lowe and his collaborators have shown that Itmap1 protects the mouse from pancreatitis and indomethacin-induced gastric injury. Ongoing studies aim at understanding the biology and function of Itmap1.

John Eisses' MD, PhD research focuses on understanding the role of epigenetic modifiers in regulating injury and recovery of the pancreas as it relates to pancreatic disease. His interests reside in the epigenetic regulation of the histone deacetylases (HDACs) in pancreatic recovery after injury, focusing on their action in distinct cell types within the pancreas – specifically pancreatic stellate cells (PSCs). Injury and inflammation activate PSCs resulting in the remodeling of the pancreatic microenvironment. Dr. Eisses postulates that an alteration in the epigenetic landscape during injury and subsequent recovery is necessary for the altered gene regulation at specific transcriptional sites within distinct pancreatic cell types. Epigenetic changes during PSC activation are required to allow ECM remodeling and to generate the necessary regenerative signals that allow pancreatic exocrine recovery. Prolonged injury or aberrant regulation of PSCs has been implicated in the development or promotion of several pancreatic diseases including chronic pancreatitis and pancreatic cancer. Ongoing studies aim to understand the important regulators of this process with an aim at developing therapeutic interventions.

Sohail Husain, MD serves as an Associate Professor of Pediatrics at the University of Pittsburgh and Co-Director of the Pediatric Exocrine Pancreatic Disorders Program at the Children’s Hospital of Pittsburgh of UPMC. He is actively engaged in determining the molecular pathways underlying pancreatitis as well as epigenetic switches that turn on regeneration and recovery after pancreatic injury. These pursuits are geared towards devising novel therapies for pancreatic disorders. Special areas of translational interest include post-ERCP pancreatitis and drug-induced pancreatitis.

David Keljo, MD, PhD, has a longstanding interest in inflammatory bowel disease (IBD). He currently has a study to evaluate the bone mineral density in pediatric patients’ IBD. It is thought that children with IBD are at risk for developing osteoporosis and its complications. Dr. Keljo is directly testing this impression by measuring bone density and markers of bone absorption in a cohort of newly diagnosed IBD patients over time. Together with this study, Dr. Keljo maintains a clinical registry of patients with IBD. This registry will be helpful in conducting outcomes research in pediatric IBD. David J Keljo, MD, PhD is the local principal investigator for several multicenter studies in IBD:

The Risk Stratification Study—evaluating the factors in newly diagnosed Crohn Disease patients that predict the rapid development of penetrating or structuring complications.

The PROTECT Study:  Examining the factors predicting response to mesalamine, steroids or biological therapies in patients newly diagnosed with Ulcerative Colitis

The GEM Study: Evaluating siblings of IBD patients who themselves have not yet developed IBD, to Determine the factors which might predict their subsequent development of IBD.

Zahida Khan, MD, PhD has longstanding clinical and research interests in pediatric liver diseases. Her research focuses on cellular approaches to liver regeneration and transplantation. Dr. Khan studies mechanisms of hepatocyte regeneration in alpha-1 antitrypsin deficiency, the most common inherited cause of pediatric liver disease and transplantation. Her work investigates critical cellular signals for liver regeneration, including (1) bile acid signaling, and (2) the liver stem cell marker LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5). Dr. Khan plans to extend these studies by developing cellular and molecular therapies for liver-based metabolic diseases.

Robert Squires Jr., MD, participates in two multicenter studies to define the epidemiology and outcome of acute liver failure in children and the pathogenesis of biliary atresia. Dr Squires is the principal investigator of the acute liver failure study. He heads the local project in the NIH consortium for biliary atresia.

Arvind Srinath’s, MD  research focuses on subspecialty medical education, in particular pediatric gastroenterology curriculum development, in addition to functional gastrointestinal disorders.

A Multicenter, Long-term Safety, Efficacy, and Pharmacokinetics Study of Lubiprostone in Paediatric Subjects Aged ≥ 6 Years to < 18 Years with Functional Constipation. This phase 3 study aims to assess the efficacy of lubiprostone in pediatric functional constipation.

Veena Venkat, MD is involved with clinical research studies related to pediatric liver disease and liver transplant outcomes.  She is an active co-investigator in iWITH, a clinical trial of immunosuppression withdrawal in stable pediatric liver transplant recipients.  Her focus has been on the long term graft health, safety outcomes and reversibility of rejection during immunosuppression withdrawal. Her clinical work with the liver transplant program has led to publications in challenging pediatric liver transplant populations including primary sclerosing cholangitis, re-transplantation, and strategies to improve patient adherence to the medical regimen.  Dr. Venkat is a co-investigator in the ChiLDReN (Childhood Liver Disease and Research Network) and has worked collaboratively to further understand the natural history and outcomes of children with cholestatic liver diseases such as biliary atresia and Alagille syndrome.   This collaboration includes her role as site lead in PRIME, A Phase I/IIa Trial of Intravenous Immunoglobulin (IVIG) Therapy Following Portoenterostomy in Infants with Biliary Atresia.