Research in my lab is devoted to understanding genetic variability as it relates to heritable resistance to cancers. We are especially interested genes that affect the occurrence of cancers associated with infection. Surprisingly, 20% of all human cancers are caused or progress as the result of infection. Viral infections, in particular, play a significant role in the occurrence of several types of tumors. It is likely that the diverse genetic makeup of modern human populations is, at least to some degree, a consequence of genetic selection by infection over evolutionary time. Hence, some individuals may be better equipped genetically than others when it comes to fighting infections by cancer causing microbes. Currently we are gathering evidence for this hypothesis by looking at cancer causing viral infections in our experimental animal model.
We are studying the genetics of resistance to the most oncogenic herpesvirus known. This is the GaHV-2 herpesvirus that causes Marek’s disease, a T-cell lymphoma in chickens. We have identified a single chicken gene BG1 as a major determinant of whether tumors form following GaHV-2 infection (Goto, Wang et al. PNAS 2009). Interestingly the two alleles in our study differ by a very small region of only 225 nucleotide base pairs (bp). The 225 bp are inserted into 3’-untranslated region of the allele that is associated with increased tumors. We are now investigating whether the 225 bp is targeted by viral or cellular microRNA that suppresses expression of BG1 therby increasing the likelihood GaHV-2-induced tumors.
In collaboration with investigators at UC Davis, we recently completed a high resolution cytogenomic study of the (very tiny) microchromosome on which BG1 is located. This microchromosome is packed with many polymorphic genes. The results of this study are indeed very interesting. We found a new region on the chromosome that is entirely unmapped even though a significant portion of the chicken genome has been sequenced. We look forward to further study of this region.
The City of Hope Electron Microscope Core Facility, for which I serve as director, is becoming increasingly busy as more members of the City of Hope scientific community use contemporary methods of electron microscopy in their work.