Research in the laboratory of Gwen A. Lomberk, Ph.D., focuses on epigenetic mechanisms underlying the regulation of pancreatic cancer cell growth and on the characterization of novel pathways for which individual components can be targeted pharmacologically.
Of particular interest are the roles of heterochromatin protein 1 (HP1) and its histone H3-K9 methyltransferases in the regulation of cell division and cancer cell growth, as well as pharmacological inhibition of these pathways. Dr. Lomberk's laboratory is investigating signaling from Aurora-A mitotic kinase to the HP1γ-G9a epigenetic pathway, which regulates mitotic progression and cancer cell growth in a manner amenable to pharmacological inhibition using combination therapy.
- Epigenetic targeting in experimental therapeutics. Dr. Lomberk's laboratory examines the effects of targeting epigenetic complexes for the treatment of pancreatic cancer, both as single agents and in combination with other therapeutic agents. The laboratory investigates not only the molecular mechanisms underlying the synergistic effects of these combinatorial therapies, but also the type of chromatin dynamics (transient vs. inherited) underlying the consequences of using small molecules to target epigenetic complexes.
- HP1 and its histone H3-K9 methyltransferases. Dr. Lomberk's laboratory studies the regulation of histone methyltransferase complexes. In particular, lab members research regulation of the histone H3 lysine 9 pathway via similar signals that dictate the histone code, and investigate how those signals affect protein-protein interactions and function in normal and disease states.
Significance to patient care
Dr. Lomberk's laboratory is focused on discovering novel molecular interactions and complex dynamics involved in epigenetic mechanisms that are triggered in response to cellular signals within the context of normal cell biology and pathophysiology. Lab members are applying this knowledge to develop better therapeutic strategies in cancer.
Pancreatic ductal adenocarcinoma (PDAC) ranks fourth as a cause of cancer death in the U.S., with a five-year survival rate of 3 to 5 percent, primarily due to its aggressive nature. In addition, PDAC is resistant to chemoradiation, which has little impact on the course of disease. Thus, there is an urgent need to discover new molecular mechanisms underlying PDAC development, to design molecularly targeted therapies.
- Editor, Medical Epigenetics journal, 2012-present
- Editor, Case Reports in Gastroenterology journal, 2010-present
- New Named Investigator, Center for Cell Signaling in Gastroenterology, Mayo Clinic, 2014
- Recipient, Young Investigator Award, International Association of Pancreatology, 2013
- Recipient, Career Development Award, Pancreatic Cancer Specialized Program of Research Excellence (SPORE) grant, Mayo Clinic, 2013