B.S., Biochemistry & Molecular Biology
B.S., Biochemistry & Biotechnology
MSU Lab: Avian Disease and Oncology Lab (ADOL)
PI: Hans H. Cheng
Satellite Lab: The Dmitrij Frishman Lab at the Technical University of Munich
PI: Dmitrij Frishman
Genome-Oriented Bioinformatics Analysis of Marek’s Disease (MD) Lymphomas
The primary focus of my doctoral dissertation is elucidating the genetic mechanisms by which Marek’s Disease Virus (MDV) induces MD T-cell lymphomas in chickens. Our project is an international collaboration between the Cheng Lab (ADOL, MSU) and the Frishman Lab (TUM) with support from the Grigoriev Lab (Rutgers) and the Delany Lab (UC Davis). Special thanks to Hongen Xu for his extensive effort in this project.
Marek’s Disease Virus is an oncogenic alphaherpesvirus that causes a CD4+ T-cell lymphomas in chickens. We know the primary viral oncogene, Meq, that drives the lymphomas, but we hypothesize that there are additional oncogenic driver mutations/genes in the host cell genome that assist Meq. We have performed whole genome sequencing, whole transcriptome sequencing, targeted 15K SNP microarrays, and cytogenetics to a cohort of MD lymphomas. This omics approach has unearthed many potential drivers, but our strongest candidate is the master regulator, IKZF1, that is altered in nearly every tumor.
To describe our findings, we will focus our efforts threefold:
-Explain the complex role of IKZF1 on MD lymphomas.
-Illustrate the cancer genome landscape of MD lymphomas.
-Illustrate the genome landscape of the latently integrated MDV in MD lymphomas.
Our work sheds new light on how MD lymphomas are created and will generate exciting new direction for the MD community.
Bioinformatics analyses and supporting scripts can be found on GitHub, are well documented, and freely available:
My GitHub: https://github.com/steepale
Hongen Xu’s GitHub: https://github.com/hongenxu/MDV_proj
Steep A. & Cheng H., The Search for Somatic Drivers in Marek’s Disease Tumors. Work presented at the NE-1334 Annual Meeting (Genetic bases for resistance and immunity to avian diseases) at the University of California. Davis, CA (October 2015).
Steep A., Xu H., Frishman D., & Cheng H., The Search for Somatic Drivers in Marek’s Disease Tumors: An Update. Work presented to the department of Genome-Oriented Bioinformatics at the Technical University of Munich. Munich, Germany (January 2016).
Steep A., Xu H., Frishman, D., & Cheng H., Searching for Somatics: The Pursuit of Genomic Drivers of Marek’s Disease Lymphoma. Work presented to the department of Bioinformatics at the Helmholtz Zentrum München. Munich, Germany (February 2016).
Steep A., Xu H., Frishman, D., & Cheng H., Searching for Somatics: The Pursuit of Genomic Drivers of Marek’s Disease Lymphoma. Work presented to the Institut für Med. Mikrobiologie, Immunologie und Hygiene at the Technical University of Munich. Munich, Germany (February 2016).
Steep A., Xu H., Frishman, D., & Cheng H., Identifying driver mutations of Marek's disease lymphomas using integrated omics screens. Work presented at the 11th International Symposium on Marek’s Disease and Avian Herpesviruses. Tours, France (July 2016).
Steep A., Xu H., Frishman, D., & Cheng H., Marek’s Disease Lymphomas: Drivers for Genetic Resistance. Work presented to the Genetics Program at Michigan State University. East Lansing, MI (January 2017).