2006 Annual Report
| Division Profile |
|---|
| Number of Faculty | 29 |
| Number of Joint Appointment Faculty | 11 |
| Clinical Fellows | 2 |
| Research Fellows | 36 |
| Number of Graduate Students | 19 |
| Number of Other Students (full and part-time) | 26 |
| Number of Support Personnel | 73 |
| Annual Total Grant Support (direct) | $5,912,596 |
| Annual Total Industry Contracts (direct) | $4,182 |
| Number of Peer Reviewed Publications | 74 |
The Division of Experimental Hematology is made up of five programs encompassing Signaling, Stem Cells, Leukemia Biology and Molecular and Gene Therapy and Cancer Biology, a shared program with the Division of Hematology / Oncology. Twenty-nine faculty now have primary or secondary appointments in the Division of Experimental Hematology. The Experimental Hematology web site provides significant information on the division activities.
The Division continues to facilitate scientific interactions via a weekly floor meeting organized by Dr. James Mulloy, a monthly external speaker seminar series co-administered with the Division of Hematology / Oncology and organized by Drs. Paul Andreassen and Michael Jordon (Hematology / Oncology) and an internal speaker seminar series administered with the Division of Immunobiology and organized by Dr. Marie-Dominique Filippi. Drs. Hartmut Geiger and Jose Cancelas are planning the 4th Annual Midwest Blood Club to be held in Cincinnati in the spring of 2007. Drs. Chris Baum, Christof v. Kalle, and David Williams are organizing the 3rd Annual Stem Cell Clonality and Genotoxicity Retreat to be held in conjunction with the American Society of Hematology meeting in Orlando, Florida in December, 2006.
The cores developed by Experimental Hematology continue to provide shared resources to a large number of faculty. For instance:
- The Vector Core has produced >1100 virus vector preparations for research purposes, over 300 products in developmental work related to large scale preps for clinical trials.
- The Vector Production Facility is currently contracting to produce five clinical gene therapy trial products, including retrovirus and AAV vector productions, with other academic institutions and private companies.
- The Translational Research Trials Office is currently assisting in 48 clinical trials (19 for Experimental Hemagology, 17 for Hematology / Oncology, 12 for other divisions). Together with the Division of Hematology / Oncology, more than 11 Investigator Initiated New Drug (IND) applications have been filed with the Food and Drug Administration and two additional INDs are in process of development.
- The Translational Trials Development and Support Laboratory (TTDSL) provides vector integration analysis for multiple gene therapy trials around the world and has instituted "complementation assignment" for Fanconi anemia patients that has been utilized by scientists and physicians from across North America. Over 500 assays have been performed by the TTDSL to establish Fanconi anemia complementation group for Fanconi anemia patients from across North America.
The Divisions of Experimental Hematology and Hematology / Oncology work closely together to enhance innovation in clinical trials and care delivery for children with serious blood diseases. This collaborative approach has been successful in facilitating the opening of a number of phase I trials in oncology, Fanconi anemia, sickle cell anemia and stem cell transplantation.
Highlights
The Experimental Hematology faculty continue to publish in a variety of peer-reviewed journals with over 74 articles published since the last annual report. Since 2003, Experimental Hematology faculty have published or co-authored 20 papers in top-tier journals, such as Science, Nature and Cell groups and New England Journal of Medicine. Grant funding continues to increase even in the setting of tightening NIH budgets. Grants have increased from $2.6 million to $7.9 million in total funding. Total funding in the Divisions of Experimental Hematology and Hematology / Oncology is now $12.4 million/year.
A major focus in the past year has been the recruitment of Dr. Punam Malik as the Program Leader of Molecular and Gene Therapy. Dr. Malik is a highly respected physician-scientist who cares for children with hematologic diseases. She has been recognized for her work in developing lentivirus vectors that express non-malignant globin genes. She is in the early stages of developing a gene therapy trial for patients with thalassemia. Dr. Malik has extensive NIH funding. She will be opening her laboratory in Experimental Hematology in September, 2006. Experimental Hematology faculty continue to play important roles in the area of gene therapy. Drs. Christof v. Kalle and Chris Baum both received the Langen Award of the Paul Ehrlich Institute. Dr. Baum received the Sir Hans Kreb Publication Award for his contribution published in Science. He was named President of the German Society of Gene Therapy. Dr. Malik received the Outstanding New Investigator Award from the American Society of Gene Therapy. Dr. Williams received the Frank Oski Award from the American Society of Pediatric Hema- tology/Oncology and the Donald Metcalf Award from the International Society of Experimental Hematology. He continues to serve as Editor-in-Chief of Molecular Therapy, the top-rated journal in the area of gene and molecular therapy.
As the Fanconi anemia program continues to successfully develop, members of the faculty of Experimental Hematology and Hematology / Oncology have developed and submitted to the NIH a program grant in this area entitled "Molecular Analysis and Translational Studies in Fanconi Anemia". This program includes collaborative investigators from Rockefeller University, the University of Minnesota and the Universidade em Curitiba, in Curitiba, Brazil. Several innovative translational, phase I trials have been developed for patients with Fanconi anemia based on basic research in this program. These trials are facilitated by the Fanconi Anemia Comprehensive Care Center which is the largest, multi-disciplinary clinic for Fanconi anemia children in the world. Drs. Andreassen and Williams were invited to present lectures on Fanconi anemia at several international scientific meetings. Dr. Meetei was awarded a prestigious Junior Faculty Scholar Award by the American Society of Hematology.
The Cancer Biology Program has continued to develop rapidly. Dr. Ratner is PI of a grant funded by the Department of Defense which supports the international Neurofibromatosis Microarray Consortium. The consortium aims to assemble and facilitate a multi-experiment integrated dataset to conduct gene expression analysis using microarray of neurofibromatosis related tumors. Dr. Ratner also has brought together a group of investigators from the UC Genome Research Institute (Drs. Thomas, Kozma) and Cincinnati Children's (Drs. Ratner, Cripe, Perentesis), and two outside sites, to form the Cincinnati Center for Neurofibromatosis Research. The goal of the group is to understand and block signaling pathways defects in Neurofibromatosis type 1. Dr. Wells work on human papillomavirus has led to a recent important paper in Molecular and Cellular Biology on the DEK oncoprotein. Dr. Ratner is serving on the NSD-B NIH study section and chairing the oversight panel for the DOD Program on Neurofibromatosis.
Another important focus of research in Experimental Hematology within the Cell Signaling and Stem Cell Biology Programs is Rho GTPases. Dr. Yi Zheng, using rational drug design, has identified a small molecule inhibitor of Rac GTPases, NSC23766, which appears to have important anti-cancer activity. The intellectual property associated with this compound has now been licensed to Amgen, Inc. and Drs. Zheng and Williams are collaborating with Amgen to develop new generation inhibitors based on the structure of the NSC compound. The study of mouse knock-outs of Rac and other Rho GTPases has led to significant new understanding of the role of the signaling molecules in blood cell development and function. These genetically modified animal models are also being utilized to define the roles of Rho GTPases in brain, eye, lung and heart development in collaboration with researchers in other divisions of Cincinnati Children's. Multiple high impact publications have resulted from this work. Dr. Theodosia Kalfa was one of two individuals to receive the Young Investigator Award from the American Society of Pediatric Hematology/Oncology for her work on Rho GTPases in red blood cell development.
