Ongoing Research Funded by DHF

The Digestive Health Foundation became a founding supporter in 2017 of a powerful new resource for digestive health medical research: The Digestive Health Foundation BioRepository. As one of only a few GI biorepositories of its kind in the world, the DHF BioRepository stores, organizes, and makes accessible (digitally, in real time) blood and tissue samples from patients and family members diagnosed with one or more of the digestive disorders treated at the Northwestern Medicine Digestive Health Center.
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Most patients with Eosinophilic Esophagitis (EoE) experience an abnormal immune-mediated response to food antigens. Identifying unique biomarkers involved in the pathogenesis of allergic inflammation could significantly improve treatments. The conversion of cell membrane arachidonic acid to ω-6 prostaglandin and ω-6 leukotriene eicosanoids during the inflammatory cascade provides many potential drug targets to impede the inflammatory process in patients with EoE. ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) have opposing influences on inflammation. Currently, there is no study on PUFA metabolism and the role these PUFAs metabolites play in the pathogenesis of EoE. Dr. Yang’s study aims to determine the ω-3 and ω-6 PUFAs metabolites/eicosanoids profile in eosinophilic esophagitis using a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics approach and to identify the unique eicosanoids or biomarker/s for diagnosis, prognosis and monitoring the therapeutic effect on EoE.
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The epithelial lining of the esophagus serves as the first line of defense to protect the underlying tissue from various external insults. Upon injury and inflammation, a rapid and efficient restoration of the esophageal epithelial barrier is needed. Failure to restore this barrier ultimately leads to pathological consequences. To date, most studies of inflammation have focused in immune cells because they are the paradigmatic inflammatory cell type. Yet immune cells are not the only cell type involved in inflammation and immunity. Epithelial cells sense and initiate inflammation, and also play a key role in the production of inflammatory molecules. It still remains unclear, though, how epithelial cells contribute to inflammation in patients with Eosinophilic Esophagitis (EoE). The investigators will determine how epithelial cells control inflammation and fibrosis in eosinophilic esophagitis. The Tétreault laboratory will also test how blocking mediators of inflammation can prevent the development and progression of EoE.
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In Eosinophilic Esophagitis (EoE), a variety of foods trigger inflammation in the esophagus.  Diet elimination remains a mainstay treatment approach, with the number and type of food triggers varying between patients. Some respond well to eliminating a single food while others require the removal of multiple foods. Although no biomarkers or testing currently exist to help pinpoint specific triggers, previous studies have found a key role for white blood cells known as T-cells. This study will assess the novel association between individual food triggers and T-cell clonality. Dr. Wechsler and his team intend to examine esophageal biopsies for evidence of the specificity of immune response of white blood cells to specific foods. The researchers will use deep sequencing of the T-lymphocyte receptor to identify how frequently unique types of T-cells appear. The team hopes this data will help explain how the immune system “learns” to respond to specific foods and, ultimately, provide a potential screen.
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One million-plus Americans have IBD, accounting for more than two million ambulatory and emergency room visits annually. This health care utilization can lead to annual medical expenditures ranging from $5,000 to $8,000 per patient. Reducing unnecessary medical costs in this patient group is paramount. Take for example, PSA tests. While PSA screening can reduce prostate cancer deaths, false-positive elevations commonly occur, especially for patients with IBD. The Kundu research group recently found that men 65 and older with IBD, who underwent prostate cancer screening at Northwestern Memorial Hospital, had higher PSA values than non-IBD controls. In addition, men with IBD had a significantly higher risk of prostate cancer. However, whether the elevation in PSA is due to IBD-related inflammation versus a true reflection of an increased risk of prostate cancer remains unclear. Study findings may optimize how men with IBD are screened for prostate cancer by better assessing their risk while at the same time reducing needless medical expenses.
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Among the busiest digestive disease centers in the country, Northwestern Medicine (NM) manages some 35,000 GI endoscopy procedures and more than 42,000 outpatient clinic visits a year. NM clinicians strive to deliver high quality, patient-centered cost-effective care with every patient encounter. Improving the quality of care relies on measuring clinical performance (i.e., “quality metrics”), implementing interventions to improve care delivery, and then re-measuring quality following the interventions. Our group utilized this approach to markedly improve the quality of colonoscopy at Northwestern thereby reducing the risk of colon cancer death after colonoscopy in the patients we serve, and subsequently published this innovative work in a leading journal (American Journal of Gastroenterology, 2015). Although the NM digestive health group has considerable quality improvement expertise, each initiative requires an analyst who has the computer and statistical skills to collect patient and procedure data from the electronic health record and interpret that data in a continuous fashion.
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Imagine a piece of food becomes stuck in your throat while eating dinner. Unfortunately, for many patients with Eosinophilic Esophagitis (EoE), this is a symptom that occurs all too often. Dysphagia, or difficulty swallowing, is a gastroenterology “red flag” that often alerts physicians to initiate a work up to determine the cause. Typically, the first step calls for an upper endoscopy to visually assess inflammation and narrowing (strictures) that can be treated. Prior data suggests that visual evaluation is not perfect. Missed strictures can lead to additional testing and delay diagnosis. Other tools have become available to assist in measuring the esophageal diameter such as the Functional Lumen Imaging Probe (FLIP), a novel technology. Dr. Patel’s research project aims to determine how accurately physicians measure esophageal diameter as compared to FLIP in patients with EoE. Better understanding the accuracy of endoscopic assessment by both visual estimation and FLIP assessment will offer insight into which tools should be used in diagnostic and therapeutic treatment of esophageal disease.
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Muscular weakness at the junction of the diaphragm and esophagus (hiatal hernia) is a common problem that may result in heartburn, difficulty swallowing, or anemia. Current surgical repair techniques have an unacceptably high hernia recurrence rate. A novel surgical material was developed at Northwestern University and has demonstrated promising results in animal and human studies. This project will investigate the efficacy of an innovative mesh suture in hiatal hernia repair, as compared to the current gold standard material. The principle outcome of interest will be measured by a non-invasive x-ray examination 6 months following surgery. The hope is that patients undergoing repair with the novel material will have lower rates of hernia recurrence without an increase in complications.
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Severe damage to the liver can profoundly affect a variety of body systems. Patients with cirrhosis suffer from excess fluid in the legs, abdomen, and chest. Medications can reduce fluid buildup but dosing is not an exact science. Inaccurate dosing can harm the kidneys, cause confusion, and even land patients in the hospital. To avoid these complications, clinicians rely on a multitude of blood and imaging tests that often require expensive equipment, drawing blood, or specially trained staff. Dr. Mazumder’s team seeks to simplify the process by testing the benefit of a decades-old technique called the Valsalva maneuver in combination with a finger photoplethysmography device (similar to a noninvasive bedside pulse oximeter). Patients hold their breath for 10 seconds, and the device measures changes in blood flow to the finger. Safely and successfully tested in individuals with heart problems to predict levels of fluid overload, the investigators. 
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A chronic bile duct and liver disease, Primary Sclerosing Cholangitis (PSC) affects more than 50,000 Americans and can progress to cirrhosis, liver failure, and bile duct cancer. Currently, the only effective therapy is liver transplantation. Better understanding the pathogenesis of PSC is urgently needed to develop new therapies. In recent cell culture and animal studies, Dr. Green and his colleagues focused on a protective cell signaling pathway: the unfolded protein response (UPR). They found that the UPR is activated when bile flow is impaired, and mice lacking UPR genes in their liver are highly susceptible to injury from bile duct obstruction. Now moving forward with the first human investigations examining UPR, Dr. Green aims to determine how it is activated in the bile ducts of patients with PSC. The team plans to study bile duct tissues obtained during endoscopic procedures performed for bile duct obstruction. The identification of “protective” genes and proteins could lead to new drug targets and, ultimately, the development of novel medical therapies.
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Normally immune cells like neutrophils protect our body against invading pathogens but sometimes they go overboard. Accumulating in tissue, they can cause cell injury in the GI tract, leading to the development of inflammatory bowel disease and potentially, colorectal cancer. While neutrophils can drive inflammation, it remains unclear just how they contribute to tumor development. Dr. Sumagin and colleagues plan to define the mechanism that allows neutrophils to both promote abnormal cell mutations and inhibit DNA repair genes. The investigators will also work to determine if neutralizing these harmful effects can prevent increased mutations and cancer.
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Medical marijuana’s popularity has grown as a treatment for tamping down the debilitating effects of Inflammatory Bowel Disease (IBD). However, no one knows if it improves intestinal inflammation— critical to treating IBD. In fact, it could be simply masking symptoms and delaying treatment. To determine if that is the case, Dr. Bertha and colleagues will compare patients in symptomatic remission (feeling well) who use marijuana to those without symptoms who do not use marijuana. Using blood and fecal tests, the researchers will assess levels of intestinal inflammation in the two groups. Findings of this study could have important clinical and societal implications as medical marijuana becomes more widespread.
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Barrett’s Esophagus (BE) occurs when damaging acid reflux causes the lining of the esophagus to change from normal to pre-cancerous tissue. Although BE can be effectively treated with acid-blocking medications, some individuals still progress to advanced disease and even cancer. Using tissue samples already collected during routine surveillance endoscopies, Dr. Komanduri and colleagues hope to identify tissue markers to indicate which BE patients are at high risk of developing cancer. Improving cancer detection in this way could allow for earlier intervention and better outcomes as well as limit the use of costly and invasive procedures.
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Eosinophilic Esophagitis (EoE) is a common cause for swallowing problems (dysphagia) in adults. Resulting in inflammation of the esophagus, EoE can severely impede the passage of food, increasing the risk of food impactions that require immediate medical attention. While diet changes and medications work well, matching the best treatment to the right patient remains challenging. Uncovering the genetic differences between EoE patients could lead to better predictors of treatment response and more personalized care. Dr. Gonsalves’s research team plans to mine Northwestern University's comprehensive clinical database (NUCATS) in combination with sophisticated genetic testing and analysis to conduct what will be the largest molecular-phenotype association study of its kind for EoE.
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The Digestive Health Foundation became a founding supporter in 2017 of a powerful new resource for digestive health medical research: The Digestive Health Foundation BioRepository. As one of only a few GI biorepositories of its kind in the world, the DHF BioRepository stores, organizes, and makes accessible (digitally, in real time) blood and tissue samples from patients and family members diagnosed with one or more of the digestive disorders treated at the Northwestern Medicine Digestive Health Center.
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A surplus of prescription pain killers continues to fuel the drug crisis in America. The accidental overdose of opioids has surpassed motor vehicle crashes, in terms of lives claimed, in this country. Nearly two-thirds of opioid pills prescribed to Digestive Health Center (DHC) patients now go unused, leaving these narcotics vulnerable to abuse or misuse within our own community. Dr. Stulberg’s intervention project will include the installation of a one-way drug collection receptacle within the DHC Clinic; provider training on opioid prescribing risks, benefits and alternatives; and patient education materials promoting opioid medication safety.
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Does constipation cause breathing problems? In some individuals with cystic fibrosis (CF), a genetic disorder typically affecting lung function and sometimes the GI tract, the answer is yes-maybe. After undergoing a bowel preparation, much like one used before colonoscopies, some CF patients have reported improvements in their breathing. To determine if there is a connection, Dr. Stein and colleagues will characterize the effect of a single bowel purge on pulmonary function tests in patients with CF who also have pancreatic insufficiency. They plan to enroll 20 patients in this pilot study.
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Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and a few other conditions, and occurs when extra fat builds up in liver cells. A serious offshoot of NAFLD, nonalcoholic steatohepatitis (NASH), can cause the liver to scar (cirrhosis) and is now the second leading cause of liver transplant. However, patients who undergo liver transplants for NASH are at particularly high risk of redeveloping NASH, which can lead to graft failure and even death. Currently, painful and invasive needle biopsies are the only way to diagnose and stage NASH after liver transplant. Dr. Rinella and her co-investigators hope to develop a blood-based alternative by identifying biomarkers that can accurately indicate the onset or recurrence of NASH. A simple blood test would allow for more frequent monitoring and earlier intervention with less discomfort and cost to patients.
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Intravenously-injected lidocaine, a numbing agent, provides pain relief without the side effects of narcotic pain medications after bowel surgery. Northwestern Memorial Hospital began using lidocaine in September 2016 at standard doses recommended by experts at other medical centers. However, a small number of patients, though, experienced side effects. Their metabolism of the drug may have resulted in higher than expected levels of lidocaine in the blood stream. Dr. Ahmad’s research team will study blood levels of lidocaine in 40 patients at various times while they are receiving the medication. The aim is to identify predisposing characteristics that put certain patients at risk for lidocaine-induced side effects to better individualize the dosing, safety and effectiveness of the drug.
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Skills matter when it comes to screening colonoscopies for colon cancer. Some doctors are better than others at finding and removing precancerous polyps that may lead to cancer if left to grow. Striving to enhance colonoscopy performance to ensure the best quality care, Dr. Duloy’s research team plans to provide feedback to GI specialists at Northwestern Medicine on their technique. The study will involve video grading by experts and pre- and post-“report cards” to measure improvement.
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The drug infliximab (Remicade) offers relief to millions of people with Crohn’s disease and ulcerative colitis. Yet, which dose is the best dose? The same dose does not work for all patients to prevent flare- ups and improve quality of life. Better personalizing the use of infliximab, Dr. Bellaguarda’s research team has designed a study to monitor and adjust dosing of the medication during two key times during the therapeutic infusion timeline. The Digestive Health Foundation grant will support a study coordinator to manage patient enrollment, monitoring and outcomes during the one-year project.
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Screening colonoscopies have been credited with turning the tide against colorectal cancer—the second leading cause of death in the United States—with early prevention and treatment. Yet barriers, from patient fears to cultural influences, keep many Americans from undergoing the potentially lifesaving procedure. Even when screening colonoscopies are scheduled, no shows and cancellations are common.
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From development to implementation, new medical advancements often don’t enter into mainstream usage without education and training. Introduced in the 1990s in Japan, minimally-invasive endoscopic submucosal dissection (ESD) has become the standard of care for not only treating but also, most importantly, curing early gastrointestinal cancers.
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Immunosuppressive drugs have made living with inflammatory bowel disease (IBD) easier. But these powerful medications have their drawbacks, especially when it comes to potentially affecting future fertility. Complicating matters, IBD often strikes people during their key reproductive years. Patients’ fertility fears may dissuade them from taking effective medication that could help them to better manage their disease.
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No one wants to hear the “C” word. Even the slightest hint of a cancer risk is, understandably, frightening—even when all signs point to a positive outcome. Chronic regurgitation of stomach acid can damage the esophagus and eventually lead to a condition known as Barrett’s esophagus (BE). Patients with BE are at risk for esophageal adenocarcinoma (cancer of the esophagus), which strikes about 3 to 4 Americans out of 100,000 each year.
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Many babies born with heart problems grow up and mature well into adulthood thanks to modern surgical advancements. In fact, one million adults currently live with some form of congenital heart disease in the United States alone. A rare congenital heart condition, single ventricle disease usually requires surgical intervention early on, with most children undergoing a common surgery known as the Fontan procedure.
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Behavioral interventions for digestive health conditions are highly effective, yet while the majority of patients are interested in these treatments, there are many barriers to accessing this care. Integrating health coaching to assist patients in make lifestyle changes and managing their health conditions may increase access to care by reducing the number of sessions needed with GI health psychologists.
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Every physician strives for and every patient expects an accurate diagnosis—no matter what the health issue. Advancements in imaging and other technologies continue to enhance diagnostic capabilities for a range of diseases, including gastrointestinal disorders. But even the most sophisticated diagnostic tools can yield erroneous results in untrained and/or inexperienced hands.
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Variations in our genetic makeup determine who we are, from hair and eye color to how we respond to drugs. Today, the growing field of personalized medicine looks to our DNA to tailor treatment so that we receive precise and appropriate care. An emerging offshoot, pharmacogenomics looks specifically at the connections between genetics and drug metabolism.
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Graduating from high school. Going away to college. Getting that first job. For many, these milestones mark the transition from childhood to adulthood, with parents and their children diligently preparing for them as they arise. Yet a young adult patient’s move from beloved pediatrician or family doctor to an unfamiliar adult care specialist is often abrupt. Learning to be in charge of your own health can be challenging, especially for those with chronic illnesses.
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Gastroesophageal reflux disease (GERD) is a common condition that often involves heartburn and/or regurgitation. If left untreated, scarring of the esophagus or “food pipe” may result. GERD leads to millions of outpatient visits annually. For some individuals, increased laxity at the end of the muscular esophagus may contribute to GERD. Assessing the extent of this laxity helps to determine the most appropriate strategies for treating the disease and preventing further damage to the esophagus.
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