Doctor of Philosophy, University of California Davis (2016)
Bachelor of Science, University of Connecticut (2010)
Inhibition of Multiple Nodes in the PI3K/Akt/mTOR Pathway Synergistically Suppresses Post-Transplant B Cell Lymphomas
WILEY. 2018: 20
View details for Web of Science ID 000419034500015
Marek's disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation.
2016; 34 (46): 5554-5561
Marek's disease (MD) is a lymphotropic and oncogenic disease of chickens that can lead to death in susceptible and unvaccinated host birds. The causative pathogen, MD virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres. MD occurrence is controlled across the globe by biosecurity, selective breeding for enhanced MD genetic resistance, and widespread vaccination of flocks using attenuated serotype 1 MDV or other serotypes. Despite over 40 years of usage, the specific mechanism(s) of MD vaccine-related immunity and anti-tumor effects are not known. Here we investigated the cytogenetic interactions of commonly used MD vaccine strains of all three serotypes (HVT, SB-1, and Rispens) with the host to determine if all were equally capable of host genome integration. We also studied the dynamic profiles of chromosomal association and integration of the three vaccine strains, a first for MD vaccine research. Our cytogenetic data provide evidence that all three MD vaccine strains tested integrate in the chicken host genome as early as 1 day after vaccination similar to oncogenic strains. However, a specific, transformation-associated virus-host phenotype observed for oncogenic viruses is not established. Our results collectively provide an updated model of MD vaccine-host genome interaction and an improved understanding of the possible mechanisms of vaccinal immunity. Physical integration of the oncogenic MDV genome into host chromosomes along with cessation of viral replication appears to have joint signification in MDV's ability to induce oncogenic transformation. Whereas for MD vaccine serotypes, a sustained viral replication stage and lack of the chromosome-integrated only stage were shared traits during early infection.
View details for DOI 10.1016/j.vaccine.2016.09.051
View details for PubMedID 27720297
Virus and host genomic, molecular, and cellular interactions during Marek's disease pathogenesis and oncogenesis
2016; 95 (2): 412-429
Marek's Disease Virus (MDV) is a chicken alphaherpesvirus that causes paralysis, chronic wasting, blindness, and fatal lymphoma development in infected, susceptible host birds. This disease and its protective vaccines are highly relevant research targets, given their enormous impact within the poultry industry. Further, Marek's disease (MD) serves as a valuable model for the investigation of oncogenic viruses and herpesvirus patterns of viral latency and persistence--as pertinent to human health as to poultry health. The objectives of this article are to review MDV interactions with its host from a variety of genomic, molecular, and cellular perspectives. In particular, we focus on cytogenetic studies, which precisely assess the physical status of the MDV genome in the context of the chicken host genome. Combined, the cytogenetic and genomic research indicates that MDV-host genome interactions, specifically integration of the virus into the host telomeres, is a key feature of the virus life cycle, contributing to the viral achievement of latency, transformation, and reactivation of lytic replication. We present a model that outlines the variety of virus-host interactions, at the multiple levels, and with regard to the disease states.
View details for DOI 10.3382/ps/pev369
View details for Web of Science ID 000371060000020
View details for PubMedID 26755654
Comparative cytogenomics of poultry: mapping of single gene and repeat loci in the Japanese quail (Coturnix japonica)
2014; 22 (1): 71-83
Well-characterized molecular and cytogenetic maps are yet to be established in Japanese quail (Coturnix japonica). The aim of the current study was to cytogenetically map and determine linkage of specific genes and gene complexes in Japanese quail through the use of chicken (Gallus gallus) and turkey (Meleagris gallopavo) genomic DNA probes and conduct a comparative study among the three genomes. Chicken and turkey clones were used as probes on mitotic metaphase and meiotic pachytene stage chromosomes of the three species for the purpose of high-resolution fluorescence in situ hybridization (FISH). The genes and complexes studied included telomerase RNA (TR), telomerase reverse transcriptase (TERT), 5S rDNA, 18S-5.8S-28S rDNA (i.e., nucleolus organizer region (NOR)), and the major histocompatibility complex (MHC). The telomeric profile of Japanese quail was investigated through the use of FISH with a TTAGGG-PNA probe. A range of telomeric array sizes were confirmed as found for the other poultry species. Three NOR loci were identified in Japanese quail, and single loci each for TR, TERT, 5S rDNA and the MHC-B. The MHC-B and one NOR locus were linked on a microchromosome in Japanese quail. We confirmed physical linkage of 5S rDNA and the TR gene on an intermediate-sized chromosome in quail, similar to both chicken and turkey. TERT localized to CJA 2 in quail and the orthologous chromosome region in chicken (GGA 2) and in turkey (MGA 3). The cytogenetic profile of Japanese quail was further developed by this study and synteny was identified among the three poultry species.
View details for DOI 10.1007/s10577-014-9411-2
View details for Web of Science ID 000335143600007
View details for PubMedID 24604153