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Defense: Novel Gene Expression Analyses to Accelerate Precision Pediatric Oncology Research

Speaker Name: 
Jacob Pfeil
Speaker Title: 
PhD Candidate
Start Time: 
Wednesday, March 4, 2020 - 2:00pm
End Time: 
Wednesday, March 4, 2020 - 3:00pm
Location: 
2300 Delaware, Double Helix Conference Room B279

Abstract: Cancer is the leading cause of death by disease for children in the United States. While there have been significant improvements in pediatric cancer therapies, there remain few treatment options available for tumors that relapse. In my thesis, I describe a novel approach for identifying new treatment strategies using unsupervised clustering algorithms to divide complex disease populations into more homogeneous subgroups. My tumor subtyping analysis revealed recurrent expression subtypes related to the tumor microenvironment across several pediatric cancers. This analysis showed significant improvements in patient outcomes when tumors had higher levels of immune infiltrate. Amplification of the antitumor immune response may further improve patient outcomes. Genome-wide dysregulation of chromatin structure correlated with increased immune infiltration. This observation led me to investigate a new class of cancer vaccine targets based on no! n-canonical protein-coding genes from usually silenced regions of the genome. I found overexpression of these epitopes in cancer tissues compared to a compendium of healthy tissue samples. I also found that the expression of these epitope sequences correlated with complete response to therapies that boost the immune system’s ability to fight cancer. Of the many drugs that show efficacy in preclinical models, very few achieve FDA approval. To improve the efficiency of the drug development process, I investigated how a class of preclinical models differs from the original patient tumor and how these differences could impact drug validation studies. Identification of these differences will inform preclinical validation studies and potentially accelerate the development of new drugs.

Event Type: 
Adancement/Defense
Advisor: 
David Haussler
Graduate Program: 
Biomolecular Engineering & Bioinformatics PhD