In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Biology

In the

School of Biological Sciences

Savannah Washburn

Will defend her dissertation

Unraveling Crohn’s disease heterogeneity through multi-omics from disease inception to progression

July 21st, 2025

10:00 am

EBB Room #1005

Zoom link: https://gatech.zoom.us/j/94653799114?pwd=HI25uymo10qTWe5YlV72IuvQRV7AMV.1

 Thesis Advisor:

Greg Gibson, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

I. King Jordan, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Abigail Lind, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Peng Qiu, Ph.D.

School of Biomedical Engineering

Georgia Institute of Technology

Saurabh Sinha, Ph.D.

School of Biomedical Engineering

Georgia Institute of Technology

ABSTRACT: Crohn’s disease (CD), one of two inflammatory bowel diseases, is characterized by chronic, transmural inflammation throughout the intestines. The cellular and molecular causes of CD remain uncertain and varying disease severity is observed across donors, suggesting alternative mechanisms may promote disease progression. This thesis addresses two central questions: (i) can gene expression across regions of the gastrointestinal tract in a treatment-naive cohort subset patients into profile subtypes, and (ii) can we identify transcriptional and proteomic biomarkers of the adverse clinical outcomes: perianal fistula and recurrent disease post-resection. To address these questions, I leverage transcriptomics and proteomics comprised of intestinal biopsies or serum sampled across different CD cohorts. 

First, persistent inflammation and mechanisms that may promote perianal-fistulizing CD was examined in a single cell transcriptomic cohort comprised of rectal biopsies of individuals with perianal-fistulizing CD. This study revealed that goblet cells, an epithelial cell, may be involved in promoting persistent inflammation. Next, inter-individual variation was explored in an inception cohort using single cell transcriptomic data from the intestines while assessing how clustering stability affects the robustness and reproducibility of single-cell analyses. This analysis stratified donors into distinct groups associated with alternative modes of disease across the intestines. Alternative splicing mechanisms was explored in a post-operative CD cohort comprised of ileum biopsies, suggesting that rectal-like splicing signatures in ileum and dysregulation of HP1g may be involved in recurring disease. Lastly, correlation between ileum gene and serum protein expression in the post-operative CD cohort was investigated, stratifying patients into groups associated with clinical attributes.

In summary, this thesis illuminates alternative mechanisms that might be involved in pathology from disease inception to advance stages of disease, providing insights that can guide personalized medicine approaches for CD.