Principle Investigator: Rocio Servin-Vences, PhD, Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern University Feinberg School of Medicine The gut and brain talk to each other all the time. Psychological stress, in particular, causes disorders of gut-brain interaction (DGBI) in 4 out of 10 U.S. adults. Chronic conditions can involve abdominal pain, diarrhea, and constipation as well as immune dysfunction and disrupted gut motility. The underlying molecular and neuronal reasons for DGBIs are a mystery, even though physicians have known for decades that stress affects the gut, especially for their digestive disease patients. Today, treatments focus mainly on relieving symptoms. Uncovering how stress disrupts gut-brain communication could inspire new therapies that get at the root causes of these disorders. The investigators hypothesize that chronic stress reprograms central and peripheral nervous systems, wreaking havoc on the GI tract. This year’s DHF award will allow Dr. Servin-Vences’ team to study chronic stress in mice to identify that reliably induce gut dysfunction. The investigators will use genetically-engineered mice that express a fluorescent protein only in neurons activated during the stress protocol. Employing state-of-the-art genetic tools, the team hopes to better understand the detailed mechanism between stress and gut function and provide invaluable insight into the impact of stress on...
Principal Investigator: Michael Rosen, MD, FACS, Professor of Surgery, Chief of the Division of GI Surgery, Northwestern Medicine, Northwestern University Feinberg School of Medicine Too much belly fat increases intra-abdominal pressure that puts any obese patient facing abdominal surgery at high risk for an incisional hernia. More than 40% of U.S. adults are obese, which presents a quandary for hernia surgeons. Should they counsel their obese patients to lose weight before surgery to better optimize their outcomes? Or should they recommend upfront surgery to avoid worsening of painful hernia symptoms and the potential need for emergency surgery? With little supporting evidence, many surgeons defer elective hernia repair in patients with a body mass index (BMI) over 35 to 40 kg/m2. As a result, 70% of obese patients who fail to lose enough weight never have surgery and 3 to 5% undergo an emergency hernia repair because of the delay in having surgery. This year, a DHF award is supporting Dr. Rosen’s team in conducting a first-ever clinical trial to evaluate the effectiveness of preoperative weight reduction strategies versus upfront surgery in hopes of improving the counseling and care of obese hernia patients with evidence-based...
Principal Investigator: Michael Rosen, MD, FACS, Professor of Surgery, Chief of the Division of GI Surgery, Northwestern Medicine, Northwestern University Feinberg School of Medicine A complication of abdominal surgery, incisional hernias occur when holes form in the abdominal wall that can dangerously allow a loop of intestine or fat tissue to bulge out. Most incisional hernias need surgical repair to close the hole to avoid painful, if not, emergency medical issues. A section of bowel, for example, could become stuck in the hernia opening and lose its blood supply. Twenty-five years ago, a landmark study showed that mesh repair reduced incisional hernia recurrence by a remarkable 50%. The use of a mesh for closing hernias instead of what was traditionally sutures alone has been the standard of care ever since. While this widely-accepted technique reduces the odds of hernias re-forming, mesh placement can lead to infections, chronic pain, reoperations, and bowel obstructions. Due to modern-day surgical advances in suturing, the investigators propose reconsidering the use of mesh for patients with small and mid-sized incisional hernias. Awarded this year’s DHF grant, Dr. Rosen’s team plan to assess in a multi-center clinical trial if primary sutures work just as well as mesh. Their ultimate goal is to significantly improve patient outcomes for the more than one million individuals who undergo life-changing hernia repair each year in the U.S. alone....
Principal Investigator: Vasilios Kalas, MD, PhD, Physician-Scientist Training Program Fellow, Division of Gastroenterology and Hepatology, Northwestern Medicine, Northwestern University Feinberg School of Medicine Co-Principal Investigator: Gabriel Rocklin, PhD, Assistant Professor of Pharmacology, Northwestern Medicine, Northwestern University Feinberg School of Medicine Inflammatory bowel disease (IBD) develops from interactions between gut microbes and genetic risk factors that trigger an out-of-control immune response. The health of some 2.5 million Americans heavily depends on IBD drugs to reduce gut inflammation and prevent infection. Unfortunately, the medications don’t work for one-third of patients and for up to 50 percent of individuals, currently available IBD drugs lose their effectiveness over time. Innovating new therapies is critical to expanding and improving life-enhancing treatment options for patients. A human protein, TNF (tumor necrosis factor) plays a key role in driving gut inflammation. Large injectable antibody drugs, like Humira and Stelara, effectively target TNF but, in the process, they block both good (TNF receptor-2) and bad (TNF receptor 1) pathways. Thanks to previous work supported by DHF, Dr. Kalas’ team has used artificial intelligence to create thousands of unique synthetic miniproteins to specifically block TNFR1. Their small size allows for the development of transformative medication easily taken by mouth. Funded by this year’s DHF award, the team plans to test the most promising of these engineered TNFR1-selective miniproteins inhibitors in animal models and human samples of IBD. This exciting research presents a great opportunity to offer millions of IBD patients an effective and convenient oral (vs infusion or injection)...
Principal Investigator: Ryan Shaw, PhD, Post-doctoral Scholar, Transplant Surgery Scientist Training Program, Northwestern Medicine, Northwestern University Feinberg School of Medicine Co-Principal Investigator: Richard M. Green, MD, Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern University Feinberg School of Medicine Liver diseases such as primary sclerosing cholangitis (PSC) inflame and scar and block bile ducts, leading to back-up of bile in the liver and blood (jaundice) and prevent the normal secretion of bile into the intestines to aid digestion. Too much bile in the liver can lead to end-stage cirrhosis of this vital organ. Up to 85% of PSC patient also have ulcerative colitis or Crohn’s disease. With few effective treatments and no cure, adults and children with PSC and other cholestatic liver diseases face cirrhosis of the liver, liver failure and death without a liver transplant. Decades of work in the Green lab have shown in mouse models the protective influence of a gene in the liver called X-box Binding Protein 1 (XBP1). Because humans have different bile acids than mice, these species-specific differences limit the direct translation of mouse XBP1 cholestasis studies to corresponding human liver diseases. Granted the DHF award this year, the investigators plan to use two recently developed strains of “humanized” mice to investigate the role of XBP1 in a more human-like system. One producing humanized bile and the other, possessing humanized livers, these unique animal models will greatly aid in the development of novel drug or genetic therapies for PSC and other liver diseases that cause back-up of bile flow through the...
