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 of 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.
Miller, MM, Robinson CM, Abernathy J, Goto RM, Hamilton MK, Zhou H, Delany ME. 2013 Mapping Genes to Chicken Microchromosome 16 and Discovery of Olfactory and Scavenger Receptor Genes near the Major Histocompatibility Complex. J Heredity (in press)
Bauer MM, Miller MM, Briles WE, Reed KM. 2013. Genetic variation at the MHC in a population of introduced wild turkeys. Animal Biotechnology 24(3):210-228. PMID:23777350
Zhang L, Katselis G, Moore RE, Lekpor K, Goto RM, Lee TD, Miller MM. 2012. MHC class I target recognition, immunophenotypes and proteomic profiles of natural killer cells within the spleens of day-14 chick embryos. Comp Develop Immunol. 37: 446-456. PMID:22446732
Zhang L, Katselis G, Moore RE, Lekpor K, Goto RM, Lee TD, Miller MM. 2011. Proteomic analysis of surface and endosomal membrane proteins from the avian LMH epithelial cell line. J Proteome Res. 10:3973-82. PMID:21776949
Gendzekhadze K, Goto RM, Miller MM, Senitzer D. 2010. The novel HLA-B*15:180 allele appears to be a recombinant B*08/B*15 allele. Tissue Antigens 76:334-335. PMID:20579314
Delany ME, Robinson CM, Goto RM, Miller MM. 2009. Architecture and organization of chicken micro-chromosome 16: Order of the NOR, MHC-Y and MHC-B subregions. J. Heredity 100:507-514. PMID: 19617522
Hee CS, Gao S, Miller MM, Goto RM, Ziegler A, Daumke O, Uchanska-Ziegler B. 2009. Expression, purification and preliminary X-ray crystallographic analysis of the chicken MHC class I molecule YF1*7.1. Acta Cystallographica F65: 422-425. PMID: 19342797
Goto RM, Wang Y, Taylor Jr, RL, Wakenell PS, Hosomichi K, Shiina T, Blackmore CS, Briles WE, Miller MM. 2009. BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken. Proc Natl Acad Sci U S A. 106:16740-16745. PMID:19805366 PMCID: PMC2757851
Sherman, M., Goto, R.M. Moore, R.E., Hunt, H.D., Lee, T.D., and Miller, M.M. 2008. Mass spectral data for 64 eluted peptide and structural modeling define peptide binding preferences for class I alleles in two chicken MHC-B haplotypes associated with opposite responses to Marek’s disease. Immunogenetics 20: 527-541.PMID:18612635 PMCID:PMC3339847
Hosomichi, K., Miller, M.M., Goto, R.M., Wang, Y., Suzuki, S., Kulski, J.K., Nishibori, M., Inoko, H., and Shiina, T. 2008. Contribution of mutation, recombination and gene conversion to chicken Mhc-B haplotype diversity. J. Immunol. 181: 3393-3399. PMID:18714011
Shiina, T., Briles, W.E., Goto, R.M., Hosomichi, K., Yanagiya, K., Shimizu, S., Inoko, H., and Miller, M.M. 2007. Extended Gene Map Reveals Tripartite Motif, C-Type Lectin, and Ig Superfamily Type Genes within a Subregion of the Chicken MHC-B Affecting Infectious Disease. J. Immunol. 178: 7162–7172. PMID:17513765
Hunt, H.D., Goto, R.M., Foster, D.N., Bacon, L.D., and Miller, M.M. 2006. At least one YMHCI molecule in the chicken is alloimmunogenic and dynamically expressed on spleen cells during development. Immunogenetics 58: 297-307. PMID:16607558
Sun, J.Y., Gaidulis, L., Dagis, A., Palmer, J., Rodriguez, R., Miller, M.M., Forman, S.J. and Senitzer, D. 2005. Killer Ig-like receptor (KIR) compatibility plays a role in the prevalence of acute GVHD in unrelated hematopoietic cell transplants for AML. Bone Marrow Transplant. 36: 525-530. PMID:16025153
Mao, A., Paharkova-Vatchkova, V., Hardy, J., Miller, M.M., Kovats, S. 2005. Estrogen selectively promotes the differentiation of dendritic cells with characteristics of Langerhans cells. J Immunol. 175: 5146-5151. PMID:16210618
Miller, M.M., Wang, C., Parisini, E., Coletta, R.D., Goto, R.M., Lee, S.Y., Barral, D.C., Townes, M., Roura-Mir, C., Ford, H.L., Brenner, M.B., and Dascher, C.C. 2005. Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family. Proc Natl Acad Sci U S A. 102: 8674-8679. (See commentary by SA Porcelli, Proc Natl Acad Sci U S A 102:8399-8400.) PMID:15939884 PMCID:PMC1150814
Miller, MM. 2004. Genome news highlights loss of chicken strains. Nature 432: 799 (Nature Correspondence signed on behalf of 46 international co-authors. PMID:15602523
International Chicken Genome Sequencing Consortium (173 authors including Miller, MM). 2004. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432: 695-716. PMID:15592404
Sun, J.Y., Gaidulis, L., Miller, M.M., Goto, R.M., Rodriguez, R., Forman, S.J., and Senitzer, D. 2004. Development of a Multiplex PCR-SSP Method for KIR Genotyping. Tissue Antigens 64: 462-468. PMID: 15361123
Miller, M.M., Bacon, L.D., Hala, K., Hunt, H.D., Ewald, S.J., Kaufman, J., Zoorob, R. and Briles, W.E. 2004. 2004 Nomenclature for the chicken major histocompatibility (B and Y) complex. Immunogenetics 56: 261-279. PMID:17373934
Delany, M.E., Krupkin, A.B. and Miller, M.M. 2000. Telomer sequence organization in birds: Evidence for ultra-long arrays and developmentally-programmed shortening in vivo. Cytogenetics and Cell Genetics 90: 139-145.
Miller, M.M., Goto, R., Taylor, Jr., R.L., Zoorob, R., Auffray, C., Briles, R.W., Briles, W.E. and Bloom, S.E. 1996. Assignment of Rfp-Y to the chicken major histocompatibility complex/NOR microchromosome and evidence for high frequency recombination associated with the nucleolar organizer region. Proc. Natl. Acad. Sci. USA 93: 3958-3962. PMID:8632997 PMCID:PMC39467
Miller, M.M., Goto, R., Bernot, A., Zoorob, R., Auffray, C., Bumstead, N. and Briles, W.E. 1994. Two Mhc class I and two Mhc class II genes map to the chicken Rfp-Y system outside the B complex. Proc. Natl. Acad. Sci. USA 91: 4397-4401. PMID:7910407 PMCID:PMC43792
Briles, W.E., Goto, R., Auffray, C. and Miller, M.M. 1993. A polymorphic system related to but genetically independent of the chicken major histocompatibility complex. Immunogenetics 39: 408-414. PMID:8436415
Miller, M.M., Goto, R., Young, S., Chirivella, J., Hawke, D. and Miyada, C.G. 1991. Immunoglobulin variable-region-like domains of diverse sequence within the major histocompatibility complex of the chicken. Proc. Natl. Acad. Sci. USA 88: 4377-4381. PMID:1903541 PMCID:PMC51662
Miller, M.M., Goto, R. and Briles, W.E. 1988. Biochemical confirmation of recombination within the B-G subregion of the chicken major histocompatibility complex. Immunogenetics 27: 127-132. PMID:3335394
Goto, R., Miyada, C.G., Young, S., Wallace, R.B., Abplanalp, H., Bloom, S.E., Briles, W.E. and Miller, M.M. 1988. Isolation of a cDNA clone from the B-G subregion of the chicken histocompatibility (B) complex. Immunogenetics 27: 102-109. PMID: 2826332
Tao, T.W., Jenkins, J.M., Vosbeck, K., Matter, A., Miller, M.M., Jockursch, B.M., Shen, A.H. and Burger, M.M. 1983. Lectin-resistant variants of mouse melanoma cells. II. In vitro characteristics. Int. J. Cancer 31: 239-247. PMID:6681806