Email

kyle.eagen@bcm.edu

Positions

Assistant Professor and CPRIT Scholar in Cancer Research

Department of Molecular and Cellular Biology
Center for Cell and Gene Therapy (CAGT)
Center for Precision Environmental Health (CPEH)
Baylor College of Medicine

Member

Dan L Duncan Comprehensive Cancer Center
Stem Cells and Regenerative Medicine Center (STaR)
Therapeutic Innovation Center (THINC)
Baylor College of Medicine

Faculty Member

Graduate Program in Cancer & Cell Biology
Graduate Program in Genetics & Genomics
Baylor College of Medicine

Addresses

Baylor College of Medicine (Office)

M512F DeBakey Building
1 Baylor Plaza, BCM130
Houston, TX 77030
United States
Phone: (713) 798-3560

Baylor College of Medicine (Lab)

M513 DeBakey Building
1 Baylor Plaza, BCM130
Houston, TX 77030
United States
Phone: (713) 798-6082

Education

PhD from Stanford University

01/2017 - Stanford, California

BS from Cornell University

05/2008 - Ithaca, New York

Honors & Awards

NIH Director's Early Independence Award

CPRIT Scholar in Cancer Research

The Sontag Foundation Distinguished Scientist Award

Professional Interests

• Nuclear organization
• Epigenetics and chromatin
• Chromosome biology
• Fusion oncoproteins
• Cancer biology and therapeutics
• Genomics and computational biology

Professional Statement

The Eagen Lab aims to elucidate how DNA is folded inside cells. We are fascinated by chromosome structure and function at length scales from individual nucleosomes to whole nuclei. Current projects are focused on two related topics:

1. Nuclear Compartmentalization

Active and inactive genes are located in different regions of the nucleus, indicating that the spatial organization of DNA influences proper gene regulation. In particular, the spatial segregation of loci into distinct regions, or compartments, of the nucleus impacts diverse areas of biology, from aging and cancer to hematopoiesis and olfaction. Aberrant chromosome compartmentalization in a variety of diseases, including cancer, pathogenically rewires gene expression programs. We combine concepts and approaches from biochemistry with methods and analytical tools from cell biology, molecular biology, pharmacology, genomics, and computational biology to determine the molecular basis of how chromosomes are folded in three dimensions and compartmentalized within nuclei. Our long-term goal is to reveal fundamental principles underlying how the folding of chromosomes within nuclear compartments impacts biological function. Near-term goals are to identify the biomolecules that compartmentalize chromosomes, determine the mechanisms driving chromosome compartmentalization, and establish causal relationships between nuclear compartmentalization and gene regulation. This fundamental knowledge is essential to define the pathophysiology of, and to ultimately therapeutically intervene in, diseases of altered nuclear compartmentalization.

2. Fusion Oncoprotein Biochemistry

Chromosome rearrangements can lead to gene fusions, where parts of two different genes combine to form a new, hybrid gene. Often, these fusions occur in coding regions and, in cancer, give rise to fusion oncoproteins. Many fusion oncoproteins control transcription, but most of the fusions that regulate gene expression lack enzymatic activity, so we are only beginning to understand how they function. We discovered that the BRD4-NUT fusion oncoprotein alters DNA folding, creating a nuclear compartment and upregulating transcription. We are branching out to study how other fusion oncoproteins function as well. Rather than studying a particular cancer, we take a biochemical approach and focus on how enigmatic fusion oncoproteins regulate chromatin structure and gene expression. These studies complement our interest in and enrich our understanding of how chromosomes are organized within nuclear compartments. By coupling fundamental biochemistry with cancer biology, we aim to reveal new molecular mechanisms of how fusion oncoproteins function that provide clues about chromosome folding in healthy cells. Fusion oncoproteins are unique to cancer cells, thereby marking them as precisely defined and highly selective therapeutic vulnerabilities. Therefore, our research also lays a foundation to devise new interventions for aggressive cancers that are driven by fusion oncoproteins.

Websites

Selected Publications

• Rosencrance CD, Ammouri HA, Yu Q, Ge T, Rendleman EJ, Marshal SA, Eagen KP "Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment." Mol Cell. 2020 Apr 2;78(1):112-126. Pubmed PMID: 32243828
• Ge T, Rosencrance CD, Eagen KP "Contact Mapping to Unravel Chromosome Folding." Trends Biochem Sci. 2019 Dec 1;44(12):1089-1090. Pubmed PMID: 31677956
• Eagen KP "Principles of Chromosome Architecture Revealed by Hi-C." Trends Biochem Sci. 2018 Jun 1;43(6):469-478. Pubmed PMID: 29685368
• Eagen KP, Hartl TA, Kornberg RD "Stable Chromosome Condensation Revealed by Chromosome Conformation Capture." Cell. 2015 Nov 5;163(4):934-946. Pubmed PMID: 26544940

Funding

Recruitment of First-Time, Tenure-Track Faculty Members - #RR210082

Grant funding from Cancer Prevention & Research Institute of Texas

Chromatin Structure as a Therapeutic Vulnerability in Cancer

R Accelerated Award - #22-25794

Grant funding from Alex’s Lemonade Stand Foundation for Childhood Cancer

GENOME ORIGAMI: Refolding Aberrant Chromosome 3D Structure for Treating NUT Carcinoma

Distinguished Scientist Award

Grant funding from The Sontag Foundation

Transcriptional Regulation and Drug Sensitivity Through Chromosome 3D Structure Rewiring by a Brain Tumor Fusion Oncoprotein

U01 Award - #U01CA294062

Grant funding from National Cancer Institute

Overcoming Limitations of BET Inhibition in NUT Carcinoma