The proposed K22 application """"""""Human Endogenous Retroviral Sequences, a Tool to Study the Role of Centromeres in Human Cancer"""""""" will investigate the sequences of endogenous retroviruses in the centromeres of the human genome, which are currently unavailable in the world's genome databanks, and will develop centromere sequence markers to understand the role centromeres play in cancer. Specifically, the candidate will sequence and characterize endogenous retroviruses in human centromeres and discover informative DNA substitutions that can be used as centromere markers. In addition, the applicability of these markers in determining the role centromeres play in breast cancer, as well as leukemia/lymphoma will also be evaluated. Hence, conventional and Deep-sequencing approaches will be used to identify mutations in the centromere markers associated with cancer. This information could begin to provide the genomic foundation for understanding the role each chromosomal centromere plays, and could potentially result in improved methodologies for studying genetic defects and cancer. The candidate earned his Ph.D. In Biomedical Sciences with a concentration in Virology and is currently a postdoctoral fellow at the University of Michigan studying human endogenous retroviruses. The candidate's ultimate career goal is to become an independent scientist investigating the role endogenous retroviral sequences in the human genome play in HIV infection, genetic diseases, and cancer biology. To ensure success with this proposal and his career development and transition to independence in translational cancer research, the candidate has placed himself in a supportive research environment at the University of Michigan, rich in senior world leader cancer investigators who use next generation sequencing analysis and genomic, as well as bioinformatics approaches in the study of cancer and human genetics. Recognizing the limitation of the candidate's cancer biology background, key elements of his career development plan includes enrolling in courses and seminars in Bioinformatics and Cancer biology and obtaining further experimental and computational training in these areas. The training proposed will contribute substantially to the candidate's scientific development and will greatly assist him in attaining his ultimate goal of achieving independence in research.
This project will uncover DNA sequence information in areas not currently available through the human genome project, and will develop pioneering research strategies to study human centromeres in health and disease. As centromeric endogenous retroviruses appear to have unique sequences in different chromosomes, the information obtained in this project will provide new geographic points that may help the community of genome researchers map the complete sequence of the centromeres. These centromere markers will prove to be extremely valuable for assessing the role centromeres play in poorly understood genetic disorders and cancers. The written critiques and criteria scores of individual reviewers are provided in essentially unedited form in the Critique section below. Please note that these critiques and criteria scores were prepared prior to the meeting and may not have been revised subsequent to any discussions at the review meeting.
|Contreras-Galindo, Rafael; Dube, Derek; Fujinaga, Koh et al. (2017) Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors. J Virol 91:|
|Contreras-Galindo, Rafael; Fischer, Sabrina; Saha, Anjan K et al. (2017) Rapid molecular assays to study human centromere genomics. Genome Res 27:2040-2049|
|Contreras-Galindo, Rafael; Kaplan, Mark H; Dube, Derek et al. (2015) Human Endogenous Retrovirus Type K (HERV-K) Particles Package and Transmit HERV-K-Related Sequences. J Virol 89:7187-201|
|Zahn, Joseph; Kaplan, Mark H; Fischer, Sabrina et al. (2015) Expansion of a novel endogenous retrovirus throughout the pericentromeres of modern humans. Genome Biol 16:74|