The Teitelbaum Research Laboratory focuses on problems associated with intestinal failure, whereby the gastrointestinal tract fails to permit the normal absorption of nutrients and is reliant on parenteral (intravenous) nutrition. Our laboratory has three main areas of focus:
Total Parenteral Nutrition and Intestinal Immune Function:
Our laboratory focuses on examining the local factors expressed by immunocytes (intraepithelial lymphocytes, IEL) which promote intestinal epithelial cell apoptosis and growth. We use two models: villus atrophy (parenteral nutrition) and villus growth (short bowel syndrome). Total parenteral nutrition (TPN), or the absence of enteral nutrition, is commonly used on a clinical basis. A major consequence of patients receiving TPN is a loss of systemic and particularly mucosal immune function. This can lead to an increased incidence of infectious complications. A long-standing project in our laboratory is to understand what mechanisms contribute to these complications. One potential source of organisms entering the host is via a loss of epithelial barrier function. We have shown that the use of TPN results in major changes in the mucosal immune populations; and that many of these changes result in epithelial cell proliferation, apoptosis and loss of barrier function
Our Lab is on the front cover of the American Journal of Physiology, August, 2013. For an abstract click HERE:
Short bowel syndrome, or the lack of sufficient intestine to sustain life, is a devastating clinical problem in children and adults. A number of attempts have been made to manipulate the remaining bowel to promote adaptation, and increase absorptive function. Unfortunately, none of these have been uniformly successful, and many have a high associated morbidity. The goal of this project is to use distractive forces, applied in a linear direction, to promote bowel lengthening.
April, 2008: The Teitelbaum Laboratory was just awarded a 3 year grant from the Hartwell Foundation to continue this work: www.thehartwellfoundation.org
January, 2011: The Teitelbaum and Brei/Luntz Laboratories were awarded the Ted Kennedy Family Team Excellence Award. This award is for production of an extraordinary and significant piece of work by a team of at least two faculty from current or recent collaboration in teaching or research at the College of Engineering.
Our laboratory has found that the expression of angiotensin
converting enzyme in the intestinal mucosa is highly correlated to
epithelial cell apoptosis. Use of enalaprilat, an angiotensin converting
enzyme inhibitor (ACE-I), can markedly down-regulate epithelial cell
apoptosis, and decrease the local expression of tumor necrosis factor
alpha (TNF-α). More recent work showed that downstream to ACE action,
blockade of the AT1a receptor can also very effectively treat colitis.
Note the marked improvement in histology in mice treated with losartan, candesartan, or a compound constructed at UM, deschloro-losartan (DCL) designed to decrease systemic exposure to AT1a-receptor antagonist. Note also the marked decline in epithelial cell apoptosis (TUNEL staining) with these drugs.