Pathology

In November 2004, the Division of Clinical Mass Spectrometry under the direction of Dr. Ken Setchell joined the Department of Pathology & Laboratory Medicine. The joining of Mass Spec with Pathology brought together the expertise of Dr. Setchell and the technical resources of his division with Pathology to enhance the overall research and clinical programs of Pathology & Laboratory Medicine. This new testing platform will expand the diagnostic capabilities of lab services as well as enhance the technical capabilities of the division by bringing this state-of-the-art technology and applying it to many facets of clinical lab testing.

Utilizing mass spec methodology for a number of important drug assays including immunosuppressants Sirolimus and Tacrolimus and the anticonvulsant drug Topiramate, will be important for monitoring drug levels and understanding the pharmacokinetics of these drugs, particularly in pediatric patients. Combining resources will greatly increase the capabilities of the GLP lab to provide reference testing support for clinical trials and related pharmaceutical studies.

In addition to clinical application of mass spec, Ken Setchell has an active independent research program applying mass spec to the diagnosis and treatment of many diseases such as genetics defects that affect the synthesis and metabolism of cholesterol and bile acids in the liver. The mass spec facility is also involved in studies investigating the role of phytoestrogens in disease prevention and treatment. Mass Spec has developed methodologies for analysis of phytoestrogens and is playing a prominent role in collaboration with many international research groups studying the health benefit of these natural bio-active plant constituents. This work in Dr. Setchell's lab has led to the filing of several patents on the application of these compounds. Other studies ongoing in this laboratory include the anti-cancer effects of the disulfate conjugate of ursodeoxycholate (SUDCA). These studies form part of the licensing agreement with Axcan Pharma in Montreal. As a result, Axcan Pharma is currently pursuing phase 2 and phase 3 clinical trials of SUDCA to determine its potential role in colon cancer prevention.

Dr. Gail Deutsch continues her research program with a focus to define how multipotential cells of the embryonic foregut endoderm give rise to different organs, including thyroid, lung, liver, pancreas and proximal GI tract. Defining how lineage decisions are made in the mammalian embryo will enhance the ability to direct cell differentiation from stem cells for novel treatment of respiratory, endocrine and digestive disorders. Dr. Deutsch has developed close working collaborations with Drs. James Wells and Aaron Zorn (Division of Developmental Biology) and Dr. Jeff Whitsett (Pulmonary Biology).

Pathology has a well established core lab with a long history of supporting numerous research groups using the combined morphologic based approach with molecular based technology. Two NIH funded core labs now exist within the division.

• One is a program under the direction of Mitch Cohen, MD, Division of Gastroenterology and Nutrition, which established the Cincinnati Center for Growth and Development. Under this support the lab provides extensive morphology and pathologic support for a number of investigators with research focuses on various aspects of pediatric digestive disease and intestinal development.
• A second core lab has been established in collaboration with the Division of Immunobiology and the Division of Allergy and Immunology (under the direction of Dr. Marsha Wills-Karp) and will involve a multidisciplinary approach to study the role of interleukin 13 and experimental asthma. This core lab has enhanced its capabilities by upgrading its electron microscopy (EM) resources. The division has purchased a new Hitachi 7600 transmission EM equipped with a digital camera and an Hitachi 3000N scanning EM to expand its research capabilities.

Dr. Margaret Collins is actively collaborating with Drs. Marc Rothenberg and Phil Putman to support their eosinophilic disorders program. This group has sponsored an international conference held at Cincinnati Children's to develop close ties with the families of patients suffering with this disorder.

Dr. Deutsch is very actively involved with a national multicenter study to better characterize pediatric interstitial lung disease to improve the diagnosis of these disorders and the management of their pulmonary disease. This group is in the process of reclassifying these lung diseases as well as establishing a centralized database and tissue bank to support research in these areas.

Dr. Kevin Bove is an active member of a national multicenter study looking at biliary atresia. He is organizing the pathology studies and collection of patient tissue samples in collaboration of Drs. Jorge Bezzera and Ken Setchell in expanding the liver disease program here at Cincinnati Children's and numerous participating pediatric medical centers.