MOB Approach to Understanding Genomic & Functional Features Shared by Osteosarcoma & BMP Cancer
Monday, December 16, 2024
10:00 AM-12:00 PM
BIOMED PhD Thesis Defense
Title:
Multiomics-based (MOB) Approach to Understanding Genomic and Functional Features Shared by Osteosarcoma and Bone Metastatic Prostate (BMP) Cancer
Speaker:
Waleed Iqbal, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Alessandro Fatatis, MD, PhD
Professor of Pharmacology, Physiology and Pathology
College of Medicine
Drexel University
Details:
This research identifies key molecular and epigenetic drivers of tumor cells’ survival and growth in the skeleton by investigating bone-metastatic prostate cancer and primary osteosarcoma, through the integration of gene expression and methylation data using statistical and machine learning approaches. Aim 1 focused on developing methodologies for analyzing methylation and gene expression data, including the design and analysis of the novel mm285 mouse methylation array. These approaches were applied in Aim 2 to bone-tropic prostate cancer, verifying the inverse relationship between the androgen receptor and the cytokine Interleukin-1beta and identifying differential methylation as a regulatory mechanism.
Additional analyses highlighted the role of the chemokine receptor CX3CR1 and also compared bone-metastatic prostate adenocarcinoma to neuroendocrine prostate cancer that metastasized to soft tissues. In Aim 3, a random forest model identified 140 genes differentiating bone metastatic from non-bone metastatic prostate cancers, with 88 showing consistent trends in primary osteosarcoma and 8 linked to significantly worse patients’ survival. Methylation data revealed 85 CpGs correlated with these genes, including 54 CpGs with positive and 31 with negative correlations, implicating enhancer-mediated activation and methylation-induced repression. These findings highlight critical regulatory elements and provide a foundation for experimental validation of the newly acquired information with the ultimate goal of identifying novel therapeutic targets for the treatment of both primary and secondary bone tumors.
Contact Information
Natalia Broz
njb33@drexel.edu