Marcia M. Miller, Ph.D. Research

Research in my lab is devoted to understanding genetic variability as it relates to heritable resistance to cancers and infections. We are especially interested in polymorphic genes that affect the occurrence of cancers associated with infection. Surprisingly, at least 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 herpes virus known. This is the GaHV-2 herpes virus that causes Marek’s disease, a T-cell lymphoma in chickens. We have identified a single chicken gene BG1, a gene within the chicken MHC, 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 role of BG1 in T cell maturation and whether the 225 bp insert is targeted by viral or cellular microRNA that suppresses expression of BG1 protein thereby increasing the likelihood GaHV-2-induced tumors.
 
In a second project also focused on polymorphic genes we are defining the function of avian MHC class I-related (MR1) molecules. We postulate that chicken molecules, like their human counterpart MR1, have a role in immune responses to bacteria. These avian genes may be a means for limiting the presence of foodborne bacterial pathogens in poultry products.
 
I also serve as director of the City of Hope Electron Microscopy and Atomic Core Facility where I assist members of the City of Hope scientific community in applying contemporary methods of electron microscopy in their work. We recently added serial block face scanning electron microscopy (SBF-SEM) as a new service. SBF-SEM is a powerful means for quantitative EM and for visualizing the three dimensional structure within cells and the structural interactions between cells in tissues.  Other newly available methods include correlative light and electron microscopy (CLEM), scanning transmission electron microscopy (STEM) and elemental analysis by energy-dispersive X-ray spectroscopy (EDS).   See the EM/AFM Core Facility website for more information.