“Centro Interdisciplinario de Neurociencia de Valparaíso”.
Research Area: ion channels biophysics and genetics
Molecular Sensors Laboratory, Professor David Naranjo
Ph.D. in Neuroscience, Universidad de Valparaíso, Chile (2014).
Biochemist, Universidad Austral de Chile, Chile (2009)
Degree in Biochemistry, Universidad Austral de Chile, Chile (2009)
E-mail: hans.moldenhauer at cinv.cl
Fax: (56)-(32)-250 8027
Address: Centro Interdisciplinario de Neurociencia de Valparaíso.
Facultad de Ciencias, Universidad de Valparaíso.
Gran Bretaña 1111. Playa Ancha. Valparaíso. Chile.
Gene therapy is one of the most promising areas in medicine for the treatment of genetic disorders. The main difference with classical therapies is that here DNA is used as a drug, to repair or to express the right product of a mutant gene.
Until now, all the efforts are destined to understand, develop and treat classical genetic disorders like; Cystic fibrosis and Myotonic dystrophy for example, but little is known and done in channelopathies, area involving ion channel malfunctions as; Long QT syndrome, Episodic Ataxia Type 1, Myokymia and Hypomagnesaemia.
One of the biggest problems that I see in the gene therapy field is the little knowledge about structure and function of the malfunctioning protein. For that reason I believe that the fusion between these two worlds; genetics and ion channel structure and function, is promising in results that will improve the treatment and development of new technical approaches for channelopathies.
In my PhD thesis, I have worked in ion channel biophysics, a main project in TRPA1 and different side projects in others TRP channels. With the support and guide of Drs. Ramon Latorre and Osvaldo Alvarez and the collaboration of Drs. Ardem Patapoutian and Jorg Grandl, I started the journey for find the temperature sensor and the binding sites of a new antagonist for the cold activated channel TRPA1. All my work under the guide of my two advisors gave me a huge training in the ion channel structure and function, field. I think that this proposal is a necessary prior step in my career for moving forward into Genetics, the next critical step in my training toward development of molecular tools for ion channels gene therapy.
In this scheme, I am starting to work with Dr. David Naranjo in an excellent and very ambitious project that fuses these two worlds. In this project we want to understand how the tetramerization process of ion channel in vivo systems occurs. For that reason, we will use a well characterized K+ channel, Shaker, in a well understood model, Drosophila melanogaster. The most exciting part of this project is the possible outcoming results. Whether the subunits mix in a random way or not, the results by itself will be informative to understand the tetramerization dynamics of ion channel in the living animal, a necessary understanding for the
correct development of new gene therapy approaches. This research using Drosophila melanogaster is what I feel I need to improve before I introduce myself in the genetics research area, to achieve my final objective, gene therapy in channelopathies.
Looking forward in the future, when I finishing my post doc with Dr. Naranjo, I want to move in a second post doc in the gene therapy field for complement my learning and begin my own research lines in channelopathies and gene therapy. Many ion channels have pathological variant that may have a dominant negative effect, but until now nothing is known about, how to induce the expression of one isoform over the others. This will be a good way to up- or down-regulate the function of a defective protein. I am particularly interested in the understanding de splicing process to be able to modify the expression pattern of a gene, and control its function. This kind of question and others are that I want to answer, for those reasons my focus will be continue working in biophysics but now and for the future, with a hand on a genetic approach.
- Carrasquel-Ursulaez W, Moldenhauer H, Castillo JP, Latorre R & Alvarez O. (2015) Biophysical analysis of thermosensitive TRP channels with a special focus on the cold receptor TRPM8. Temperature. 2015. DOI:10.1080/23328940.2015.1047558.
- Jabba S, Goyal R, Sosa-Pagán JO, Moldenhauer H, Wu J, Kalmeta B, Bandell M, Latorre R, Patapoutian A, Grandl J. (2014) Directionality of Temperature Activation in Mouse TRPA1 Ion Channel Can Be Inverted by Single-Point Mutations in Ankyrin Repeat Six. Neuron. 82(5):1017-1031
- Moldenhauer H, Latorre R Grandl J. (2014) The pore-domain of TRPA1 mediates the inhibitory effect of the antagonist 6-Methyl-5-(2-(trifluoromethyl)phenyl)-1H-indazole. PLoS One. 9 (9): e106776
- Pertusa M, Moldenhauer H, Brauchi S, Latorre R, Madrid R, Orio P (2012). Mutagenesis and temperature-sensitive little machines. In: Mutagenesis, Mishra, R. Ed., InTech Open Access publisher. Chapter 11, pp 221-246
- Salazar M, Moldenhauer H, Baez-Nieto D. (2011) Could an allosteric gating model explain the role of TRPA1 in cold hypersensitivity?. (Journal Club) The Journal of Neuroscience. 31(15):5554-56
- Bittner CX, Valdebenito R, Ruminot I, Loaiza A, Larenas V, Sotelo-Hitschfeld T, Moldenhauer H, San Martín A, Gutiérrez R, Zambrano M, Barros LF. (2011) J Neurosci. 31(12):4709-13
- Barros LF, Bittner CX, Loaiza A, Ruminot I, Larenas V, Moldenhauer H, Oyarzún C, Alvarez M. (2009) Kinetic validation of 6-NBDG as a probe for the astrocytic glucose transporter GLUT1 109 Suppl 1:94-100