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Institution
Albert-Ludwigs-Universität Freiburg
Host
Institution
National Institutes of Health, Bethesda MD
Mentor: Cynthia E. Dunbar, M.D. Hematology Branch, National Heart,
Lung and Blood Institute
Hematopoietic Stem Cells (HSC) are a primary target for gene therapy based on their ability to give rise to all hematopoietic and potentially other cell lines as well as their long term repopulating ability. Neither the clonal composition of the hematopoietic system nor the renewal capacity of stem cells have been studied directly in large animals and humans. Retroviral vectors introduce a molecular marker that is specific for each individual cell due to random integration in the cell's genome. After ex vivo transduction this unique integration site is passed on to the clonal progeny emerging from mitosis.
Recent achievements in gene transfer efficiency in a monkey model at the NIH and a new PCR technique developed in our lab in Freiburg have resulted in the first in vivo molecular evidence of the polyclonal character of marked hematopoietic recovery after bone marrow transplantation in a large animal model. The sequence data generated in this clonality analysis also enables follow-up of specific clones by conventional PCR. My work at the NIH consists of establishing PCRs for several clones and screening peripheral blood samples and sorted (T, B. NK, Granulocytes, Monocytes) or cultured cells from multiple time points. The analysis of the longitudinal activity and semiquantitative contribution to the different cell lineages allows us to explore on a molecular level, self-renewal, pluripotency, and long-term activity of marked hematopoietic progenitor cells in vivo.
The understanding of hematopoiesis is not only of theoretical but also of practical importance for clinical stem cell transplantation and gene therapy.
lt is a great opportunity and experience to work and live in the States for a while and I have met a lot of fantastic people. I like the ‚how are you' even though it often does not mean much, but I think it is better than ignoring each other as frequently happens in Germany. lt is very easy to adapt and feel at home in Washington, maybe because it is nothing special to be foreign, since around 70% of the population is African American and all the embassies and institutions attract an international mixture of people.
This also applies to the lab, especially because it is a government institution that takes great care not to under-represent minorities. lt is actually rather difficult to find ,true' Americans among the post-docs.
There are some complications involved with the fact that the NIH is not a university; for example a traditional clinical clerkship is not possible. As well, as in my case, it has not been easy to continue a project that I had already started and I do not recommend others trying this. Even with the modern methods of communication it is very difficult to get good supervision. Also I spent at least 6 weeks ordering materials and organizing before I could really start working.
At the beginning a lot of funny situations arose simply because of misunderstandings due to language barriers.
You gain many new friends which for me is one of the biggest advantages of going abroad.
The most humurous event I recall when thinking of BMEP occured in Boston when Jens, Rahul and I rented a sail boat. I reassured Rahul that everything was under control even though the wind was blowing quite strongly from time to time. I will never forget the expression on his face when suddenly the boat inclined so much that Rahul got a wet bottom and almost believed his last hour had come. Moreover, our own expressions of nonchalance did not reassure him at all!
Don't miss the FORUM, it is helpful to meet people who have the same troubles (visa, car, insurance, lab...) and it is nice to have someone to visit!
Be prepared to spend a lot of money. The easist way to do this is to obtain a German Citibank account, but they don't exist everywhere (check out their list of branches).