Gwen Lomberk, PhD

Chief, Division of Research; Director, Basic Science Research; Department of Surgery; Associate Professor of Surgery and Pharmacology & Toxicology

Contact Information

Education

PhD, Cancer Biology, Mayo Graduate School, 2002

Research Experience

Cell Cycle Proteins
Cell Nucleus Shape
Chromatin
Chromatin Assembly and Disassembly
Chromatin Immunoprecipitation
Chromosomal Proteins, Non-Histone
Epigenesis, Genetic
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Histone Code
Histone-Lysine N-Methyltransferase
Kruppel-Like Transcription Factors

Leadership Positions

Chief, Division of Research
Director Basic Science Research, Department of Surgery

Research Interests

Epigenomic-based pharmacology has the potential to serve as a robust tool to improve the future treatment of pancreatic cancer (PDAC), which is the focus of my research program. My laboratory seeks to contribute to the field of experimental therapeutics through combined inhibition of a genetic-to-epigenetic pathway to treat PDAC, as an important and provocative consideration for harnessing the capacity of cell cycle inhibitors in efforts to not only enhance future use of epigenetic inhibitors, but also translate similar approaches to other genetic-to-epigenetic pathways to control cancer growth. Our data demonstrate that the combined inhibition of the G2/M regulator, Aurora A, and the H3K9Me pathway is synergistic to inhibit PDAC growth. By inducing cell cycle arrest through inhibition of AURKA, the mitotic machinery is exposed longer to the H3K9Me pathway, which is well known to regulate centromere structure, triggering a cytotoxic mechanism that involves perturbation of normal mitotic progression to ultimately end in mitotic catastrophe, an attractive outcome in oncology. Inhibition of the H3K9 pathway, specifically in mitosis, offers a unique therapeutic approach not characteristically considered when utilizing epigenetic agents, which are generally applied in the context of modulating gene expression during interphase. My long-term research goals are broadly aligned with studying the regulation of histone methyl transferase complexes via similar signals that dictate the histone code and how those signals affect protein-protein interactions and function, as well as the type of dynamics (transient vs inherited) underlying the consequences of epigenetic targeting. Thus, we remain passionate about discovering molecular interactions and complex dynamics involved in epigenetic mechanisms triggered in response to cellular signals within the context of normal cell biology and pathophysiology and applying this knowledge to develop better therapeutic strategies in cancer.

New Insights Into Pancreatic Cancer: Notes from a Virtual Meeting.

(Hessmann E, Schneider G, 1(st) Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting.) Gastroenterology. 2021 Sep;161(3):785-791 PMID: 34089734 SCOPUS ID: 2-s2.0-85112794735 06/06/2021
Computational modeling reveals key molecular properties and dynamic behavior of disruptor of telomeric silencing 1-like (DOT1L) and partnering complexes involved in leukemogenesis.

(Stodola TJ, Chi YI, De Assuncao TM, Leverence EN, Tripathi S, Dsouza NR, Mathison AJ, Volkman BF, Smith BC, Lomberk G, Zimmermann MT, Urrutia R.) Proteins. 2021 Aug 20 PMID: 34414607 SCOPUS ID: 2-s2.0-85114677469 08/21/2021
Correction to: Molecular mechanics and dynamic simulations of well-known Kabuki syndrome-associated KDM6A variants reveal putative mechanisms of dysfunction.

(Chi YI, Stodola TJ, De Assuncao TM, Leverence EN, Tripathi S, Dsouza NR, Mathison AJ, Basel DG, Volkman BF, Smith BC, Lomberk G, Zimmermann MT, Urrutia R.) Orphanet J Rare Dis. 2021 Jun 01;16(1):247 PMID: 34074320 PMCID: PMC8170813 SCOPUS ID: 2-s2.0-85107273180 06/03/2021
Homotypic cell cannibalism, a cell-death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer.

(Cano CE, José Sandí M, Hamidi T, Calvo EL, Turrini O, Bartholin L, Loncle C, Secq V, Garcia S, Lomberk G, Kroemer G, Urrutia R, Iovanna JL.) EMBO Mol Med. 2021 May 07;13(5):e14243 PMID: 33960146 PMCID: PMC8103076 SCOPUS ID: 2-s2.0-85105133639 05/08/2021
Corrigendum to: Homotypic cell cannibalism, a cell-death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer (EMBO Molecular Medicine, (2012), 4, 9, (964-979), 10.1002/emmm.201201255)

(Cano CE, José Sandí M, Hamidi T, Calvo EL, Turrini O, Bartholin L, Loncle C, Secq V, Garcia S, Lomberk G, Kroemer G, Urrutia R, Iovanna JL.) EMBO Molecular Medicine. 7 May 2021;13(5) SCOPUS ID: 2-s2.0-85105133639 05/07/2021
A GATA6-centred gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer.

(Kloesch B, Ionasz V, Paliwal S, Hruschka N, Martinez de Villarreal J, Öllinger R, Mueller S, Dienes HP, Schindl M, Gruber ES, Stift J, Herndler-Brandstetter D, Lomberk GA, Seidler B, Saur D, Rad R, Urrutia RA, Real FX, Martinelli P.) Gut. 2021 Apr 12 PMID: 33846140 04/14/2021
Metabolomic profiling of pancreatic adenocarcinoma reveals key features driving clinical outcome and drug resistance.

(Kaoutari AE, Fraunhoffer NA, Hoare O, Teyssedou C, Soubeyran P, Gayet O, Roques J, Lomberk G, Urrutia R, Dusetti N, Iovanna J.) EBioMedicine. 2021 Apr;66:103332 PMID: 33862584 PMCID: PMC8054161 SCOPUS ID: 2-s2.0-85104049834 04/17/2021
Molecular mechanics and dynamic simulations of well-known Kabuki syndrome-associated KDM6A variants reveal putative mechanisms of dysfunction.

(Chi YI, Stodola TJ, De Assuncao TM, Leverence EN, Tripathi S, Dsouza NR, Mathison AJ, Basel DG, Volkman BF, Smith BC, Lomberk G, Zimmermann MT, Urrutia R.) Orphanet J Rare Dis. 2021 02 05;16(1):66 PMID: 33546721 PMCID: PMC7866879 SCOPUS ID: 2-s2.0-85100579633 02/07/2021
Inactivation of the Euchromatic Histone-Lysine N-Methyltransferase 2 Pathway in Pancreatic Epithelial Cells Antagonizes Cancer Initiation and Pancreatitis-Associated Promotion by Altering Growth and Immune Gene Expression Networks.

(Urrutia G, de Assuncao TM, Mathison AJ, Salmonson A, Kerketta R, Zeighami A, Stodola TJ, Adsay V, Pehlivanoglu B, Dwinell MB, Zimmermann MT, Iovanna JL, Urrutia R, Lomberk G.) Front Cell Dev Biol. 2021;9:681153 PMID: 34249932 PMCID: PMC8261250 SCOPUS ID: 2-s2.0-85116952280 07/13/2021
Interpreting Sequence Variation in PDAC-Predisposing Genes Using a Multi-Tier Annotation Approach Performed at the Gene, Patient, and Cohort Level.

(Zimmermann MT, Mathison AJ, Stodola T, Evans DB, Abrudan JL, Demos W, Tschannen M, Aldakkak M, Geurts J, Lomberk G, Tsai S, Urrutia R.) Front Oncol. 2021;11:606820 PMID: 33747920 PMCID: PMC7973372 SCOPUS ID: 2-s2.0-85102941394 03/23/2021
Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

(Wang Y, Wu J, Chen H, Yang Y, Xiao C, Yi X, Shi C, Zhong K, He H, Li Y, Wu Z, Zhou G, Rao Q, Wang X, Zhou X, Lomberk G, Liu B, Zhao J, Ge J, Zhou W, Chu X, Chen C, Zhou X, Wang L, Guan K, Qu L.) Sci Adv. 2021 Jan;7(5) PMID: 33571129 PMCID: PMC7840125 SCOPUS ID: 2-s2.0-85099945962 02/12/2021
Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells

(Wang Y, Wu J, Chen H, Yang Y, Xiao C, Yi X, Shi C, Zhong K, He H, Li Y, Wu Z, Zhou G, Rao Q, Wang X, Zhou X, Lomberk G, Liu B, Zhao J, Ge J, Zhou W, Chu X, Chen C, Zhou X, Wang L, Guan K, Qu L.) Science Advances. 27 January 2021;7(5) SCOPUS ID: 2-s2.0-85099945962 01/27/2021

Surgery