Tzong-Hae Lee, MD, PhD
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Dr. Lee and his group have played a major role in the development and application of molecular assays addressing complications associated with transfusion. Using a technique that amplifies DNA sequences one billion times, Dr. Lee is focused on the development and application of highly sensitive PCR- assays for monitoring and molecular investigation of infectious agents and transfused donor white blood cells.
Under Dr. Lee’s direction, his group has continued to fine-tune, in-house optimization techniques so that an assay for a virus with known sequence, may be rapidly developed and deployed.
Chimerism is defined as the stable persistence of a population of cells from one individual within another. When the chimeric population is small, the term microchimerism (MC) is used. MC is important because it is proof that two types of cells can exist together in an organism. Understanding MC may be a key to new therapies for organ and stem cell transplantation. It may also give greater understanding of the immune system as a whole.
To this end, Dr. Lee and Dr. William Reed developed a battery of assays specifically designed for the characterization and quantification of MC. Of great interest to the BSRI investigators are MC in trauma patients and in pregnant women (maternal circulation), the two populations where MC has been detected.
MC and Trauma
Dr. Lee’s group is testing samples -- collected through collaborations with University of California at Davis and the University of Washington -- from a group of trauma patients who received infusions of multiple units of blood. The BSRI group detected microchimeric cells up to three years post-transfusion and the MC can be traced to a single donor. Not all trauma patients become microchimeric, but if certain conditions are met, recent findings indicate that MC may be established and its occurrence predicted by testing samples collected from donors and recipients before transfusion. The prevailing hypothesis is that stem cells are being transfused, and surprisingly, even if the donor unit is leukoreduced.
In order to further understand MC, a mouse model was established at the University of California, San Francisco. The mice used have specific genes deleted or knocked-out of their genetic make-up and hence they do not produce a specific type of cells. By systematically utilizing a panel of genetically modified mice (knock-out mice) as transfusion recipients, Dr. Lee is able to determine which cells are immunologically important for the establishment of MC. Prolonged persistence of donor cells in mice was identified in one type of knock-out recipient mice. Dr. Lee is currently designing experiments that would modulate the expression of these genes. This research should have an impact on transplantation science and could ease the effects of “rejection” when unrelated donors provide solid organs or cells.Maternal MC
MC is also detected in the maternal circulation. In an earlier BSRI study, fetal DNA or cells released into a pregnant woman’s circulation was characterized by amplification of paternal DNA derived from the mother’s blood during pregnancy. This technique was shown to be a reliable method for typing or characterizing fetal DNA without being invasive or using amniocentesis. Another project related to fetal microchimerism is a study investigating the causal relationship between MC and autoimmune diseases like rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. This research could help clinicians understand the mechanisms of fetal-induced autoimmune disease in mothers and help guide scientists toward prevention of this problem.