Kyle P. Eagen, Ph.D.
Assistant Professor and CPRIT Scholar in Cancer Research
Positions
- Assistant Professor and CPRIT Scholar in Cancer Research
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Department of Molecular and Cellular Biology
Center for Cell and Gene Therapy (CAGT)
Center for Precision Environmental Health (CPEH)
ÌÇÐÄÊÓƵ of Medicine
- Member
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Dan L Duncan Comprehensive Cancer Center
Stem Cells and Regenerative Medicine Center (STaR)
Therapeutic Innovation Center (THINC)
ÌÇÐÄÊÓƵ of Medicine
- Faculty Member
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Graduate Program in Cancer & Cell Biology
Graduate Program in Genetics & Genomics
ÌÇÐÄÊÓƵ of Medicine
Addresses
- ÌÇÐÄÊÓƵ of Medicine (Office)
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M512F DeBakey Building
1 Baylor Plaza, BCM130
Houston, TX, 77030
United States
Phone: (713) 798-3560
- ÌÇÐÄÊÓƵ of Medicine (Lab)
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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.
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
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Rosencrance CD, Ammouri HA, Yu Q, Ge T, Rendleman EJ, Marshal SA, Eagen KP. " " Mol Cell. 2020 Apr 2; 78 (1) : 112-126.
Pubmed PMID: . -
Ge T, Rosencrance CD, Eagen KP. " " Trends Biochem Sci. 2019 Dec 1; 44 (12) : 1089-1090.
Pubmed PMID: . -
Eagen KP. " " Trends Biochem Sci. 2018 Jun 1; 43 (6) : 469-478.
Pubmed PMID: . -
Eagen KP, Hartl TA, Kornberg RD. " " Cell. 2015 Nov 5; 163 (4) : 934-946.
Pubmed PMID: .
Funding
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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
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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
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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
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U01 Award
#U01CA294062 - Grant funding from National Cancer Institute
- Overcoming Limitations of BET Inhibition in NUT Carcinoma
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Research Grant
#Q-2232-20250403 - Grant funding from The Welch Foundation
- Elucidating the Mechanism and Dynamics of Chromatin Contacts Mediated by a Molecular Bridge
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