Reinhold Penner, MD, PhD
- Researcher (Professor) and Associate Member
Cancer Biology Program
University of Hawaii Cancer Center
- Adjunct Professor
Department of Cell and Molecular Biology
John A. Burns School of Medicine, University of Hawaii at Manoa
- Director of Research
Center for Biomedical Research
The Queen's Medical Center
- MD, University of GĂ¶ttingen, 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, GĂ¶ttingen, Germany
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.
- Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y. (2008). TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nature Med, Jul;14(7):738-47; Epub 2008 Jun 8; PubMed Central PMCID: PMC2789807. PMED ID: 18542050.
- 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.
- Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP, Scharenberg AM. (2001). ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature, May 31;411(6837):595-9. PMED ID: 11385575.
- Hoth M, Penner R. (1992). Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature, Jan 23;355(6358):353-6. PMED ID: 1309940.
Publication list via PubMed
- N. Palafox (PD), R. Penner (Full Project PI)
NIH/NCI U54 CA143727
"Identification of pro-inflammatory molecules involved in Areca nut carcinogenesis" Identification of the active chemical components of Areca (betel nut) that mediate calcium signals in immunocytes and determine the molecular mechanisms by which calcium is mobilized in these cells.
A. Fleig (PI), R. Penner (Co-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 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.
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.