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.

Modeling post-translational modifications and cancer-associated mutations that impact the heterochromatin protein 1α-importin α heterodimers.

(Zimmermann MT, Williams MM, Klee EW, Lomberk GA, Urrutia R.) Proteins. 2019 Nov;87(11):904-916.
Emerging epigenomic landscapes of pancreatic cancer in the era of precision medicine.

(Lomberk G, Dusetti N, Iovanna J, Urrutia R.) Nat Commun. 2019 Aug 28;10(1):3875.
Aurora kinase B-phosphorylated HP1α functions in chromosomal instability.

(Williams MM, Mathison AJ, Christensen T, Greipp PT, Knutson DL, Klee EW, Zimmermann MT, Iovanna J, Lomberk GA, Urrutia RA.) Cell Cycle. 2019 Jun;18(12):1407-1421.
CBX5/G9a/H3K9me-mediated gene repression is essential to fibroblast activation during lung fibrosis.

(Ligresti G, Caporarello N, Meridew JA, Jones DL, Tan Q, Choi KM, Haak AJ, Aravamudhan A, Roden AC, Prakash YS, Lomberk G, Urrutia RA, Tschumperlin DJ.) JCI Insight. 2019 May 16;5.
Enhancer of Zeste Homologue 2 Inhibition Attenuates TGF-β Dependent Hepatic Stellate Cell Activation and Liver Fibrosis.

(Martin-Mateos R, De Assuncao TM, Arab JP, Jalan-Sakrikar N, Yaqoob U, Greuter T, Verma VK, Mathison AJ, Cao S, Lomberk G, Mathurin P, Urrutia R, Huebert RC, Shah VH.) Cell Mol Gastroenterol Hepatol. 2019;7(1):197-209.
Disruption of FOXP3-EZH2 Interaction Represents a Pathobiological Mechanism in Intestinal Inflammation.

(Bamidele AO, Svingen PA, Sagstetter MR, Sarmento OF, Gonzalez M, Braga Neto MB, Kugathasan S, Lomberk G, Urrutia RA, Faubion WA Jr.) Cell Mol Gastroenterol Hepatol. 2019;7(1):55-71.
Inactivation of NUPR1 promotes cell death by coupling ER-stress responses with necrosis.

(Santofimia-Castaño P, Lan W, Bintz J, Gayet O, Carrier A, Lomberk G, Neira JL, González A, Urrutia R, Soubeyran P, Iovanna J.) Sci Rep. 2018 11 19;8(1):16999.
Mechanisms Underlying the Regulation of HP1γ by the NGF-PKA Signaling Pathway.

(Seo S, Mathison A, Grzenda A, Podratz J, Calvo E, Brimijoin S, Windebank A, Iovanna J, Lomberk G, Urrutia R.) Sci Rep. 2018 10 10;8(1):15077.
Co-occurrence of a maternally inherited duplication and a paternally inherited pathogenic variant in in a child with growth retardation and severe short stature: atypical Weaver syndrome or evidence of a dosage effect?

(Polonis K, Blackburn PR, Urrutia RA, Lomberk GA, Kruisselbrink T, Cousin MA, Boczek NJ, Hoppman NL, Babovic-Vuksanovic D, Klee EW, Pichurin PN.) Cold Spring Harb Mol Case Stud. 2018 08;4(4).
Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes.

(Lomberk G, Blum Y, Nicolle R, Nair A, Gaonkar KS, Marisa L, Mathison A, Sun Z, Yan H, Elarouci N, Armenoult L, Ayadi M, Ordog T, Lee JH, Oliver G, Klee E, Moutardier V, Gayet O, Bian B, Duconseil P, Gilabert M, Bigonnet M, Garcia S, Turrini O, Delpero JR, Giovannini M, Grandval P, Gasmi M, Secq V, De Reyniès A, Dusetti N, Iovanna J, Urrutia R.) Nat Commun. 2018 05 17;9(1):1978.
Epigenetics of gastrointestinal diseases: notes from a workshop.

(Marks DL, Olson RL, Urrutia R, Billadeau DD, Roy N, Calin GA, Fabbri M, Koutsioumpa M, Iliopoulos D, Ordog T, Huebert R, Sarmento O, Bamidele AO, Faubion W, Lomberk GL, Siveke J, Ahuja N, Iovanna J, Hlady RA, Robertson K, Kisiel J, Pin CL, Fernandez-Zapico ME.) Epigenetics. 2018;13(4):449-457.
EGFR (ErbB) signaling pathways in pancreatic cancer pathogenesis

(Williams M, Lomberk G, Urrutia R.) Pancreatic Cancer. 11 April 2018:383-408.

Gwen Lomberk, PhD

Gwen Lomberk, PhD

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

Contact Information

Education

Research Experience

Leadership Positions

Research Interests

Publications