Research

The overall focus of the Peripheral Nerve Surgical Research Laboratories is to investigate the pathology, mechanisms, and treatments for traumatic peripheral nerve injuries. Led by Matthew Wood, PhD, and Susan Mackinnon, MD, the lab employs histology, electrophysiology, and in vivo imaging, combined with surgical and experimental treatments, to study the biological processes of nerve regeneration within the context of surgical repair. Translational research projects encompass a true “bed to benchside” research approach. Research produced by the lab has led directly to changes in the clinical treatment of patients with peripheral nerve injury and to new understanding of nerve regeneration.

The Plastic and Reconstructive Surgery Bioengineering Lab, led by Matthew Wood, PhD, focuses on augmenting and improving surgical response to major tissue injuries through bioengineered therapies. The laboratory is investigating ways to improve bioengineered tissue replacements, such as scaffolds used for skin grafting, fat grafting, and nerve grafting. They are currently focused on how to improve nerve graft alternatives, such as nerve guidance conduits or tissue-engineered acellular nerve allografts. The lab is also investigating how electrical stimulation protocols are effective in promoting nerve regeneration to better understand electrical stimulation’s ability to promote other forms of tissue regeneration.

The long-term goal of the Eghtesady Research Laboratory is to eradicate congenital heart disease. The lab, led by Pirooz Eghtesady, MD, PhD, investigates the causes of congenital heart disease, hypothesizing that perinatal infection during cardiac morphogenesis is responsible. Currently, the lab is studying women with pregnancies affected by congenital heart disease. By comparing biospecimens in non-pregnant and pregnant women, they are investigating the influence of environmental risk factors on the development of heart defects in the offspring. The lab is also studying offspring models exposed to infections in early gestation with the goal of better understanding virally-induced congenital heart disease.

Since its founding in 2005, the NIH-funded Thoracic Immunobiology Laboratory has studied innate immune response, tumor immunology and transplantation immunology. The laboratory performs basic scientific investigations as well as translational studies directly related to patient care. The lab’s innate immune response research, directed by Andrew Gelman, PhD, deals with the pre-clinical development of inhibitors of toll-like receptors and CD39, testing their efficacy in preventing lung graft ischemia-reperfusion injury. The lab’s research on tumor immunology, led by Dr. Alexander Krupnick, MD, has focused on understanding the mechanism of tumor tolerance induction. Transplantation immunology research, led by Daniel Kreisel, MD, PhD, has focused on the alloimmune response after lung transplantation.

The Intestinal Adaptation Laboratory at St. Louis Children’s Hospital seeks to better understand how the intestine adapts to massive intestinal loss. Ultimately, their research hopes to allow patients to live a more normal lifestyle and avoid the complications associated with intravenous nutrition. The laboratory is led by Brad Warner, MD, and Jun Guo, MD, PhD, MPH, MS, who blend sophisticated molecular biology techniques with clinically-focused applications. This technology utilizes transgenic, knockout, and mutant mice in a unique intestinal resection surgical model. In addition, the lab uses laser capture microdissection microscopy to study adaptation in isolated cells of the small intestine.

Ultimately, the Zayed Laboratory aims to develop effective new therapeutic modalities for the treatment of diabetic patients with progressive peripheral arterial disease (PAD). The laboratory, led by Mohamed Zayed, MD, PhD, studies the mechanisms that influence arterial collateral formation and peripheral arterial atheroprogression in the setting of diabetes. Two questions drive the lab’s current research: Why do diabetic patients have a significantly higher incidence of developing PAD? And are they at increased risk of malperfusion at healing surgical sites? The lab’s research explores the hypothesis that arterial phospholipid tissue expression and processing play a central role in this process, making use of biochemical assays, in vivo models, and a biobank of vascular tissue specimens.

The Nupam Mahajan Lab investigates how tyrosine phosphorylation regulates epigenetic processes that affect cellular homeostasis, immune impairment and cancer cell survival. The laboratory has developed a new class of a small molecule inhibitor for ACK1, an oncogene with epigenetic activity in prostate, breast and lung cancers. The lab has uncovered that ACK1/TNK2 is activated in a majority of aggressive triple negative breast cancers, and shown that knockdown ACK1 expression can substantially suppress the invasiveness and proliferation advantage of cells in vitro. The lab has also discovered a novel class of WEE1 inhibitors as well as a previously unknown function of WEE1, a cell cycle regulator that has a dual role as an epigenetic modifier that maintains histone transcript levels.

The Kiran Mahajan Lab researches epigenetic regulators promoting survival, adaptability and metastasis of lethal cancers, particularly hormone refractory prostate cancers. The laboratory is currently working to characterize novel small molecule inhibitors that they have identified as having potent anti-tumor activity against metastatic prostate cancers. The research team, led by Kiran Mahajan, PhD, is interested in dissecting epigenetic regulators driving castration resistance and drug resistance. Their research focuses on WD40 repeat containing proteins, bromodomain proteins and ubiquitin ligases as epigenetic regulators of disease specific targets. Through these studies, they hope to develop a robust pharmacogenomics pipeline to advance novel inhibitors as cancer therapeutics.

Led by William Hawkins, MD, the Washington University SPORE in Pancreas Cancer at Siteman Cancer Center is designed to address the deadliest form of pancreatic cancer, pancreatic ductal adenocarcinoma, through collaborative, interdisciplinary research. The Pancreas SPORE includes four research programs. One focuses on immune system responses shown to restrain tumor development and progression. Another is developing a drug to improve survival rates for pancreatic cancer patients. The third project screens combinations of drugs that may inhibit molecular pathways that support tumor survival in pancreatic cancer. The fourth project develops and tests personalized vaccines for pancreatic ductal adenocarcinoma patients based on their genetic makeup.