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Faculty

Andrea Fleig, PhD, MBA

Andrea Fleig, PhD
  • Researcher (Professor) and Associate Member
    Cancer Biology Program
    University of Hawaii Cancer Center
  • Director
    Clinical Research
    The Queen's Medical Center
  • Academic Appointments

  • Adjunct Professor
    John A. Burns School of Medicine
    University of Hawaii at Manoa

Degree

  • PhD (Biomedical Sciences)
    University of Hawaii
  • Professorial Degree (Habilitation, Zoology)
    University of Goettingen, Germany
  • Executive MBA
    University of Hawaii Shidler College of Business

Research Focus

The focus of my research interest revolves around cellular signaling events as they relate to health and disease. Over the past 20 years I have been using biophysical and pharmacological approaches elucidating ion channel function and its relationship to cell signaling. Mediated by very fruitful national and international collaborations, I was able to incorporate molecular aspects to this work, which has led to the original identification and biophysical as well as functional characterization of several novel ion channels, including the channel-kinase TRPM7.

The results of my work identified TRPM7 as a central mechanism for magnesium homeostasis, and possibly trace metal regulation, in mammals. TRPM7, it turns out, is also centrally involved in mammalian embryonic development, and aggravation of outcome measures in ischemic stroke. Recent developments have placed TRPM7 at the center of cell proliferation and cell cycle progression, prompting my research interests to move into tumor biology. In addition to elucidating the mechanisms involved in magnesium-dependent control of cell proliferation, we have screened natural product libraries for pharmacological activity on this target and identified Waixenicin A, a molecular produced by a Hawaiian soft coral, as a potent an highly specific inhibitor of TRPM7 and proliferative activity of tumor cells. The TRPM7 gene, its function and its pharmacological modulation by this compound have resulted in three patent application and numerous publications in the journals of Cell and Nature.

My research will continue to focus on TRPM7 within tumor biology expanding into animal models. Since magnesium homeostasis is regulated by TRPM7, any positive or negative interference with TRPM7 may lead to hypo- or hypermagnesemia, possibly with secondary calcemia. We therefore, currently assess the magnesium levels and pharmacological interference thereof, in an experimental colon cancer model to assess the role of TRPM7 in tumor growth. Furthermore, the screening efforts have resulted in a large three-year research grant to develop a high-throughput screening center at The Queen's Medical Center. This is in collaboration with the UH Cancer Center, Hawaii Pacific University, Hamamatsu Photonics, and others and will have a focus to develop new therapeutic and diagnostic tools for cancer, as well as other diseases.

Selected Publications

  • Zhang Z, Faouzi M, Huang J, Geerts D, Yu H, Fleig A, Penner R. (2014). N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation. Oncotarget, Sep 15;5(17):7625-34. PMED ID: 25277194.
  • Ryazanova L, Hu Z, Suzuki S, Chubanov V, Fleig A, Ryazanov A. (2014). Elucidating the role of the TRPM7 alpha-kinase: TRPM7 kinase inactivation leads to magnesium deprivation resistance phenotype in mice. Scientific Reports, Dec 23;4:7599. doi: 10.1038/srep07599. PMED ID: 25534891.
  • Yu H, Zhang Z, Lis A, Penner R, Fleig A. (2013). TRPM7 is regulated by halides through its kinase domain. Cell Mol Life Sci, Mar 8. [Epub ahead of print]. PMED ID: 23471296.
  • Zierler S, Yao G, Zhang Z, Kuo WC, Poerzgen P, Penner R, Horgen FD, Fleig A. (2011). Waixenicin A inhibits cell proliferation through magnesium-dependent block of TRPM7. J Biol Che, Sep 16. PMED ID: 21926172.
  • Ryazanova LV, Rondon LJ, Zierler S, Hu Z, Galli J, Yamaguchi TP, Mazur A, Fleig A, Ryazanov AG. (2010). TRPM7 is essential for Mg(2+) homeostasis in mammals. Nature Commun, Nov 2;1:109; PubMed Central PMCID: PMC3060619. PMED ID: 21045827.
  • Castillo B, P├┐rzgen P, Penner R, Horgen FD, Fleig A. (2010). Development and optimization of a high-throughput bioassay for TRPM7 ion channel inhibitors. J Biomol Screen, Jun;15(5):498-507; Epub 2010 Apr 22. PMED ID: 20413646.
  • Nadler MJ, Hermosura MC, Inabe K, Perraud AL, Zhu Q, Stokes AJ, Kurosaki T, Kinet JP, Penner R, Scharenberg AM, Fleig A. (2001). LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature, May 31;411(6837):590-5; Erratum in: Nature, 2001 Aug 9;412(6847):660. PMED ID: 11385574.

Publication list via PubMed

Active Grants

  • Andrea Fleig, Principal Investigator
    Hamamatsu-Queen's PET Imaging, LLC
    "Hamamatsu-Queen's High-Throughput Screening Center"
    The goal of this project to develop a HTS Center in collaboration with the University of Hawaii Cancer Center, Hawaii Pacific University, University of Hilo School of Pharmacy and University of Hawaii Chemistry Department to identify novel therapeutic strategies against cancer and other diseases.
    January, 2013 - December, 2015