SUMMARY
The research team led by Gwen A. Lomberk, Ph.D., investigates epigenetic pathways in pancreatic ductal adenocarcinoma. Dr. Lomberk focuses her research on how chromatin-based regulatory mechanisms interface with the cell cycle, DNA damage response, genome stability and stress adaptation to drive tumorigenesis.
Dr. Lomberk's laboratory team defines the epigenomic circuits that underlie pancreatic ductal adenocarcinoma aggressiveness, therapeutic vulnerability and therapy resistance, with an emphasis on chromatin-modifying enzymes and related regulatory complexes. By integrating mechanistic discovery with preclinical therapeutic studies, the team translates these insights into rational combination strategies for precision cancer treatment.
Focus areas
- Epigenetic regulation of genome function. Research in the laboratory of Dr. Lomberk examines how chromatin-modifying enzymes, including lysine and arginine-methyltransferase pathways, and remodeling complexes regulate gene expression, chromatin organization, DNA repair and genome stability. These epigenetic mechanisms shape cancer cell identity, plasticity and tumor progression. These mechanisms also influence how cancer cells respond to oncogenic, environmental and therapeutic stress.
- Epigenetic control of genome stability, nuclear architecture and stress adaptation. Through her work in the program, Dr. Lomberk focuses on how epigenetic regulators coordinate with cell-cycle progression, genome maintenance pathways and nuclear architecture to preserve cellular function under stress. These systems act as stress sensors and decision points for cell-fate outcomes. Their disruption contributes to tumor progression while creating vulnerabilities that can be therapeutically exploited.
- Chromatin-driven therapeutic vulnerabilities and combination strategies. Cancer cells depend on epigenetic pathways to survive under conditions of oncogenic and treatment-induced stress. Ongoing studies characterize these dependencies and identify biomarkers that predict sensitivity to targeted therapies and rational combinations. This process enables strategies that exceed the adaptive capacity of tumor cells.
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Structural genomics and therapeutic discovery. Structural and computational approaches are integrated across the program to define how genetic variation, protein structure and molecular interactions influence epigenetic regulator function.
A dedicated structural genomics and drug discovery team led by Raul A. Urrutia, M.D., Ph.D. supports variant-aware hypothesis generation, molecular modeling and structure-guided therapeutic discovery. This approach accelerates the development of targeted inhibitors and combination strategies.
Significance to patient care
Pancreatic cancer is hard to treat because cancer cells can change, survive stress and become resistant to therapy. Dr. Lomberk studies the instructions cancer cells use to turn genes on or off. These instructions are called epigenetic programs.
By understanding how these programs help cancer cells continue growing without responding to treatment, Dr. Lomberk hopes to find new weak points in these cells. Her work may help guide the development of new drugs and drug combinations for patients who need better options. Dr. Lomberk's goal is to help treatments work better and last longer.
Professional highlights
- Senior editor, Endocrine Connections, 2024-present.
- Associate editor, Clinical Epigenetics, 2019-present.
- National Cancer Institute:
- Chairperson, Mechanisms of Cancer Therapeutics C Study Section, National Cancer Institute, 2026-2028.
- Standing member, Mechanisms of Cancer Therapeutics C Study Section, 2023-2028.
- Principal investigator, "Targeting Epigenomic Regulators at the Replication Fork in Pancreatic Ductal Adenocarcinoma," 2021-2027.
- Member, Program Committee, American Society of Human Genetics, 2025-2027.
- Member, AGA Institute Research Policy Committee, American Gastroenterological Association, 2025-2027.
- Medical College of Wisconsin:
- Director, Precision Medicine Graduate Education Program, Institute for Health and Humanity, 2024-2026.
- Joel and Arlene Lee Endowed Chair in Pancreatic Cancer Research, 2021-2026.
- Chief, Division of Research, Department of Surgery, 2017-2026.>
- Graduate School Outstanding Educator, 2023-2024.
- Graduate School Outstanding Educator, 2020-2021.