Gwen Lomberk, PhD

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

Contact Information

Biography

Education

PhD, Cancer Biology, Mayo Graduate School, 2002

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.

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 Nov 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 Oct 10;8(1):15077.
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.
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.
Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms.

(Drinane MC, Yaqoob U, Yu H, Luo F, Greuter T, Arab JP, Kostallari E, Verma VK, Maiers J, De Assuncao TM, Simons M, Mukhopadhyay D, Kisseleva T, Brenner DA, Urrutia R, Lomberk G, Gao Y, Ligresti G, Tschumperlin DJ, Revzin A, Cao S, Shah VH.) JCI Insight. 2017 Dec 21;2(24).
LSD1, a double-edged sword, confers dynamic chromatin regulation but commonly promotes aberrant cell growth.

(Kozub MM, Carr RM, Lomberk GL, Fernandez-Zapico ME.) F1000Res. 2017;6:2016.
Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts.

(Nicolle R, Blum Y, Marisa L, Loncle C, Gayet O, Moutardier V, Turrini O, Giovannini M, Bian B, Bigonnet M, Rubis M, Elarouci N, Armenoult L, Ayadi M, Duconseil P, Gasmi M, Ouaissi M, Maignan A, Lomberk G, Boher JM, Ewald J, Bories E, Garnier J, Goncalves A, Poizat F, Raoul JL, Secq V, Garcia S, Grandval P, Barraud-Blanc M, Norguet E, Gilabert M, Delpero JR, Roques J, Calvo E, Guillaumond F, Vasseur S, Urrutia R, de Reyniès A, Dusetti N, Iovanna J.) Cell Rep. 2017 Nov 28;21(9):2458-2470.
Resolution of Cochlear Inflammation: Novel Target for Preventing or Ameliorating Drug-, Noise- and Age-related Hearing Loss.

(Kalinec GM, Lomberk G, Urrutia RA, Kalinec F.) Front Cell Neurosci. 2017;11:192.
Functional validation reveals the novel missense V419L variant in associated with Loeys-Dietz syndrome (LDS) impairs canonical TGF-β signaling.

(Cousin MA, Zimmermann MT, Mathison AJ, Blackburn PR, Boczek NJ, Oliver GR, Lomberk GA, Urrutia RA, Deyle DR, Klee EW.) Cold Spring Harb Mol Case Stud. 2017 07;3(4).

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

Biography

Education

Research Interests

Publications