Reinhold Penner, MD, PhD

Reinhold Penner, MD, PhD

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Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Researcher (Professor), Cancer Biology Program, University of Hawaiʻi Cancer Center
Adjunct Professor, Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaiʻi at Mānoa
Director of Research, Center for Biomedical Research, The Queen's Medical Center

Degree(s):
MD, University of Göttingen, Germany
PhD, Pharmacology, Justus-Liebig-University of Giessen, Germany
MS, Biology, Justus-Liebig-University of Giessen, Germany
Postdoctoral Fellow, Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany

Honors

1992 - 1997, Professorship Award, Schilling Foundation for Medical Sciences, Germany
1993-present, Trustee of the Roger-Eckert Foundation
2000, Yamanouchi Foundation Award
2011, Weinman Innovator Award for Translational Research, Weinman Foundation
2012-present, Reviewer, NIH Director’s Emphasis Panel (Pioneer Awards)
2013, Excellence in Research Award, Friends of the University of Hawaiʻi Cancer Center
2013-present, Editor, Journal of Physiology, England
2014, Principal Organizer, Advances and Breakthroughs in Calcium Signaling, April 7-9, 2016, Honolulu, Hawaiʻi . Presented by the Journal of Physiology, England
2015, Lifetime Member, National Academy of Inventors, Hawaiʻi Chapter, USA
2017, Finalist and Winner, Outstanding Contribution to Drug Discovery: Enabling Biology 2016, Lilly Open Innovation Drug Discovery

Research Focus

The laboratory studies the mechanisms of inter- and intracellular signal transduction and its main goal is to elucidate the functional properties of molecular components involved in the complex regulation of secretion, excitation-contraction coupling, cell proliferation, and apoptosis. All research projects are guided by our desire to understand the relevant clinical context in which the molecular mechanisms operate, whether human disease states are causally linked or impacted, and ultimately how these mechanisms can be modified pharmacologically or genetically to treat patients. Our research primarily concentrates on four clinical areas: immune disorders (autoimmune diseases, allergy, inflammation), metabolic disorders (diabetes), anoxic disorders (stroke), and oncologic disorders (various cancers).

The approach to study signaling events is mainly at the single-cell level and employs a variety of biophysical techniques (e.g., electrophysiology and digital imaging) to assess important parameters such as ionic fluxes, membrane potential, intracellular second-messenger and calcium levels. These techniques are complemented by pharmacological, biochemical, molecular biological, and genetical tools to investigate signaling pathways in native systems (cell lines, primary and tissue cultures), in genetically modified systems (transient and/or stable transfections of cells), and in cells derived from transgenic animals. A further research focus involves drug discovery efforts using high-troughput screening aimed at developing experimental therapeutics and translational studies in defined animal models and clinical trials in humans.

Autoimmune Disease: We have discovered that the anti-bacterial drug clofazimine also acts as an immunosuppressant in memory T lymphocytes by virtue of inhibiting the potassium ion channel Kv1.3. This work forms the basis for a translational research project in which we investigate the clinical potential of clofazimine in the treatment of autoimmune diseases such as multiple sclerosis, psoriasis, diabetes type 1, and rheumatoid arthritis.

Cancer: We have identified and characterized several novel ion channels, including CRAC, TRPM2, TRPM4 and TRPM7. Several of these ion channels are linked to cell growth and proliferation of cancer cells and we are presently exploring the therapeutic potential of several novel pharmacological tools specifically directed towards these channels. We have identified possible therapeutics for ovarian and pancreatic cancer as well neuroblastoma, which we are now translating into targeted clinical trials.

Natural Products Drug Discovery: We are developing functional bioassays against various ion channels and have screened chemical and natural product libraries for pharmacological activity. This identified waixenicin A, a molecule produced by a Hawaiian soft coral, as a potent and selective inhibitor of TRPM7 that suppresses the growth of tumor cells.

Selected Publications

Faouzi M, Neupane RP, Yang J, Williams P, Penner R. (2018). Areca nut extracts mobilize calcium and release pro-inflammatory cytokines from various immune cells. Sci Rep, Jan 18;8(1):1075. doi: 10.1038/s41598-017-18996-2. PMED ID: 29348572.

Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP. (2006). CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science, May 26;312(5777):1220-3; Epub 2006 Apr 27. PMED ID: 16645049.

Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet JP. (2004). TRPM4 regulates calcium oscillations after T cell activation. Science, Nov 19;306(5700):1374-7. PMED ID: 15550671.

Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. (2002). TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell, May 3;109(3):397-407.PMED ID: 12015988.

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; PMED ID: 11385574.

Publication list via PubMed

Active Grants

R. Penner, Co-PI, A. Fleig, PI
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 Hawaiʻi Cancer Center, Hawaiʻi Pacific University, University of Hilo School of Pharmacy and University of Hawaiʻi Chemistry Department to identify novel therapeutic strategies against cancer and other diseases.
06/13-05/19

R. Penner (PI)
Queen's Research Seed Grant
"Pre-clinical and clinical efficacy of antibiotic AB1 in ovarian and pancreatic cancer" The goal of this multi-disciplinary collaboration between Dr. Penner (drug screening), Dr. Malika Faouzi (animal testing), and Dr. Michael Carney (clinical pilot study) is to determine the functional role of STIM2 in ovarian and pancreatic cancer and assess the therapeutic benefits of its pharmacological inhibition by an FDA-approved antibiotic in clinical use.
06/13-12/18