Research Activities
Bringing research from the lab bench to the bedside is what brought Dr. Christof von Kalle, the newest researcher in the
Division of Experimental Hematology at Cincinnati Children's Hospital Medical Center, from Germany to Cincinnati.
"From the bench to the bedside" means developing knowledge gained in a laboratory and applying it to the clinical treatment of patients. Kalle, the new director of the
Molecular and Gene Therapy Program in the Division of Experimental Hematology, understands that translation of knowledge into treatment is critical to treating disease, and that is why he is here.
About Vector Systems
Vector systems as well as viruses can leave stable changes in the genome of an infected cell. Interestingly, by inserting the additional viral genetic code into one of the cell's chromosomes they produce a small change in the genetic code of the cell. The change is unique to this one cell and serves as an indelible "fingerprint". For more details, visit the Molecular Medicine in Action site and select the "Viral Vectors" menu item on the left. The location where they insert their own viral codes within the billion "lines of" genetic code "programming" is different in every instance and hard to find. However, this small change in genetic code is engraved into the inheritable portion of the genome and therefore, is passed on to every cell formed from the normal cellular divisions the cells. The cells formed from these cellular divisions are called progeny or daughter cells. The code in successors of the same stem cell is therefore always identical whereas it is always different in progeny of different stem cells.
The Kalle lab has developed advanced technology that allows for the first time, the ability to detect these small changes in minute numbers of cells and to read the portion of the genetic sequence that has been changed.
This information can be used in a variety of innovative ways that were not possible before: - The success of a gene therapy can now be measured because the number of gene corrected stem cells can be counted from a small sample of blood.
- Gene therapy vectors can be improved by directly measuring their ability to transport and establish additional genetic code in stem cells.
- The daughter cells in blood and organs produced by one specific stem cell can be evaluated by tracking their presence in blood samples taken over time. This allows to "look at" the activity of a single stem cell in a living organism without using invasive or painful methods.
- The change in the genetic code generated by viruses or vectors can be evaluated as to its potential to damage a cell or an organism if an important gene has been hit.
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The Molecular and Gene Therapy Program focuses on improving the technology used for gene transfer and understanding the biology of the cells that need to receive these transfers. The hope is that this understanding will allow researchers to translate this technology into a therapy that can be used to treat diseases like cancer at the genetic level.
"We attempt to genetically modify adult stem cells - mostly cells of the bone marrow - that eventually form blood," explained Kalle. "One of the concepts is to replace a defective or missing gene (occurring in some inherited diseases) with a normal, functioning gene. We are particularly focused on developing treatment and monitoring procedures for gene therapy that are both effective and especially attentive in assuring patient safety."
Kalle hopes to build on the research he has conducted as part of international gene therapy collaborations in Germany and the research that has been done in the Division of Experimental Hematology at Cincinnati Children's. Both have been working towards implementing with improved outcomes, and are currently moving gene therapy towards approval for Phase I clinical trials. The current trials are focused towards treating Fanconi Anemia, storage diseases and cancer.
According to Kalle, the Molecular and Gene Therapy Program has been fortunate to be able to recruit several outstanding experts who are striving towards "designing even better vectors, improving the handling of stem cells and developing clinical trials."
Naturally, Kalle and his group will continue basic research to discover possible therapies for use in future trials. And with new therapies emerging, the need to study long-term effects of these treatments becomes increasingly important.
"We are getting to a stage where some of the earlier international protocols have been really effective in terms of treating children," said Kalle, "but as with every effective medication, there could be side effects developing. [We need] to find out how best to detect and prevent them."
While his move to Cincinnati brought him from overseas, Kalle is no stranger to the U.S. In 1988 he was a subintern at Albert Einstein and at Cornell Medical School in New York City, and from 1992-94 a research associate in transplantation biology at the Fred Hutchinson Cancer Research Center in Seattle, Wash. Now Kalle is ready for the opportunities that Cincinnati Children's provides.
"This is a whole program," said Kalle, "as compared to many other institutions where establishing a gene therapy program begins as a one-person show. At Cincinnati Children's, world-renowned specialists work in many of the different areas of care and research.
"Beginning with the hematopoietic research excellence of the Williams group and the other superb Experimental Hematology programs, we can collaboratively tap into their advanced understanding of hematopoietic stem cell function and the transplantation process. In addition, Cincinnati Children's offers the unique possibility to closely interact with many of the world's leading specialists for understanding and treating inherited childhood diseases. Among them, the excellence of the Hematology/Oncology and Human Genetics programs offers patients treatment in a truly exceptional environment.
"For our program, Cincinnati Children's is a premiere location for innovative research and clinical care. Our Division encourages the continuation of our program's national and international collaborations and facilitates our attempts to find, together with other scientists and physicians, new therapies for affected children and adults."
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