Thesis Defense: Thomas Rachman | August 7, 2026 | 2pm
CPCB is proud to announce the following thesis defense:
Title: Shedding Light on Cell-Free DNA in Cancer with Computational Models
Thomas Rachman
Friday, August 7, 2026 @ 2pm
Gates-Hillman Complex, Room 7101
For zoom details, please reach out to Nicole Stenger
Committee:
Oana Carja (Chair)
Russell Schwartz (Chair)
John P. Barton, University of Pittsburgh
Jeffrey West, Moffitt Cancer Center & Research Institute
Abstract: Cell-free DNA (cfDNA) is highly elevated in the blood plasma of cancer patients. Advances in the methods to detect circulating tumor DNA (ctDNA) in cfDNA samples have greatly improved the utility of blood-based cancer detection and monitoring in the clinic. However, the technology is fundamentally limited by a poor understanding of the mechanisms governing cfDNA release, degradation, and clearance. The overall goal of this thesis is to improve our understanding of cfDNA biology in cancer through the integration of computational and mechanistic models with clinical and genomic data. In the first aim, I explore the effects of spatial tumor growth on ctDNA shedding, demonstrating that spatial constraints on cell turnover can distort the clonal composition of the tumor in the blood as it evolves. In the next aim, I interrogate associations between ctDNA release and vascular geometry by integrating in-silico modeling of benign and malignant blood vessel networks with matched CD31 staining, cfDNA sequencing, and tumor volume. In the last aim, I turn from release mechanisms to the dynamics of degradation and clearance, revealing their profound impact on cfDNA concentration and fragment length through a simple mathematical model validated on multiple experimental and clinical datasets. I use these results to argue that saturation of hepatic clearance, rather than increased ctDNA release, explains both the elevated quantity of cfDNA and reduced fragment length in cancer. In total, this thesis derives novel insights into cfDNA biology through the careful application of mechanistic models to patient data and raises important questions for the clinical translation of cfDNA analysis.