Human Metabolomics

Professor Jan Frank, Ph.D.

Staff

Head of division
Professor Jan Frank, Ph.D.
Phone: +49-228 73 2817
Fax: +49-228 73 2024
Email: jan.frank@nutrition-research.de
Office hours for students: Thursday, 12:30-14:30

Curriculum vitae

EDUCATION

August 2004 - Ph.D. in Food Science, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden

September 2000 - Diploma (“Master of Science”) in Human Nutrition and Home Economics (“Diplom Oecotrophologe”), Bonn University, Germany

PROFESSIONAL EXPERIENCE

September 2012-present - Professor of Human Metabolomics, Department of Nutrition and Food Science, University of Bonn, Germany
September 2009-August 2012 - Group Leader (Bioavailability and Bioactivity of Micronutrients), Institute of Biological Chemistry and Nutrition, Hohenheim University, Stuttgart, Germany

June 2006 - Guest researcher, School of Biomedical and MolecularSciences, University of Surrey, Guildford, UK

March-May 2006 - Guest researcher, Hugh Sinclair Human Nutrition Group, School of Food Biosciences, University of Reading, UK

March 2005-August 2009 - Senior Researcher, Institute of Human Nutrition and Food Science, Christian Albrechts University (CAU), Kiel, Germany

August 2004-February 2005 - Postdoctoral researcher, Department of Food Science, SLU, Uppsala, Sweden

May-September 2003 - Collaborative research with Prof. Traber at the Linus Pauling Institute, Oregon State University, Corvallis, OR,USA

February 2001-July 2004 - Ph.D. student, Department of Food Science, SLU

October 2000-January 2001 - Guest researcher, Department of Food Science, SLU

July 1997-September 1998 - Guest student, research project at the Department of Food Science, SLU

October 1993-September 2000 - Student of Human Nutrition and Home Economics (“Ernährungs- und Haushaltswissenschaften”) a the University of Bonn, Germany

Memberships

Editorial Boards

Plant Foods for Human Nutrition (Springer)
since 2011
Co-Editor Europe for Nutrition (Elsevier)
since 2012
BioFactors (Wiley)
since 2013
Editor for Metabolism and Nutrition in Oncology (Thieme)
since 2013

Professional Societies

Deutsche Gesellschaft für Ernährung e.V. (German Nutrition Society)
since 1996

Oxygen Club of California
since 2002

New York Academy of Sciences
since 2004

NuGO - The European Nutrigenomics Organisation
since 2007

Society for Free Radical Research - Europe
since 2009

Gesellschaft für angewandte Vitaminforschung e.V.
since 2009, Member of the Board of Directors since 2012

Universitätsbund Hohenheim e.V.
since 2009

Life Science Center at the University of Hohenheim
since 2010
Food Security Center
since 2011

Voluntary Organisations

Bridge To Africa (BTA)
since 2008

On-call scientist for the AAAS Science and Human Rights Program
since 2008

Secretary
Ulrike Schroeter
Phone: +49-228 73 2065
Fax: +49-228 73 2024
Email: ulrike.schroeter@uni-bonn.de
Tuesday 9:00-17:00
Thursday 9:00-17:00
Friday 13:00-17:00

Lecturer
PD Dr. Simone Diestel
Phone: +49-228 73 3812
Fax: +49-228 73 2024
Email: s.diestel@uni-bonn.de

Research

The research of Dr. Diestel focuses on the role of cell adhesion molecules in the development of the nervous system and the synaptic plasticity in the adult brain.

Project 1:
In this project Dr. Diestel investigates the molecular mechanisms of adult neurogenesis in the olfactory system. Postnatally born neurons that are generated in the periventricular zone of the lateral ventricle migrate through the rostral migratory stream to the olfactory bulb. Here they start radial migration into different olfactory layers and differentiate into different types of interneurons, a process which is ongoing in the adult. Therefore, this model may allow for future cell replacement therapies in neurodegenerative diseases of the brain since, for example, the generation of tyrosine hydroxylase-positive neurons could provide a basis for a potential therapeutic approach for Parkinson’s disease. Also, the study of different interneuron subtypes may provide knowledge that helps to understand the development of schizophrenia in which the GABAergic interneuron system is disturbed in different brain areas.
Dr. Diestel’s published results demonstrate a proliferate effect of the neural cell adhesion molecule NCAM on neural stem cells in vivo. The increased proliferation of NCAM overexpressing neural stem cells results subsequently in an increase of migrating neural precursors destined for the olfactory bulb. The molecular mechanisms are not yet known. The aim of this project is to identify the basic mechanisms of NCAM-induced neurogenesis by expression of specific genes and siRNA approaches in vivo.
Furthermore, Dr. Diestel will investigate the role of NCAM in the differentiation of interneurons into different neuron types. This approach will give further insights into basic questions of differentiation of neurons in general. Some in vitro data already showed a possible role of NCAM in neuron differentiation.

Project 2:
This part of Dr. Diestel’s research deals with the cellular mechanisms of NCAM and the related cell adhesion molecule L1. She has shown earlier that both cell adhesion molecules are posttranslationally modified by ubiquitin thereby regulating either endocytosis or intracellular trafficking, respectively. This aspect is most interesting since endocytosis and intracellular trafficking are indispensable for cell migration and neurite outgrowth during neural development and synaptic plasticity in adult brain.
Therefore, Dr. Diestel will investigate how ubiquitination of NCAM and L1 is regulated. In general, ubiquitination of proteins is regulated by ubiquitin ligases which bind to the target protein and attach ubiquitin covalently to the target protein. The reciprocal process – removal of ubiquitin from its target protein – is catalyzed by de-ubiquitinating enzymes. Several hundred ubiquitin ligases and de-ubiquitinating enzymes have been identified in mammalian cells. Therefore, a proteomical approach is necessary to investigate the regulation of NCAM’s and L1’s ubiquitination. Using a protein macroarray Dr. Diestel plans to identify ubiquitin-dependent proteins that bind to NCAM or L1, respectively. After verification of the result with alternative methods it is planned to investigate the physiological role of the regulated ubiquitination of L1 and NCAM with specific focus on cell migration and neurite outgrowth during neural development.

Project 3:
In addition to ubiquitin-dependent proteins, NCAM and L1 interact with several other molecules of which only a small fraction has been identified so far. The interaction of NCAM or L1, respectively, is indispensable for most of the described functions. The above explained protein macroarray will also be useful to identify other, ubiquitin-independent interaction partners of NCAM and L1. Some interesting candidates have already been identified. Some are currently under investigation and others will in the future be verified by alternative methods. The physiological role of identified interactions will be analyzed by novel in vitro and in vivo methods. This part of Dr. Diestel’s research will give further insights into the basic mechanisms of cell adhesion in the nervous system

Publications

Original and review articles
1.      Goschzik T; Cremer H; Schmitz B; Diestel S (2012). Phosphorylation of threonine-803 of NCAM140 targets NCAM for endocytosis – submitted –

2.      Wobst H; Faraidun H; Sekulla A; Schmitz B; Dreiseidler M; Höhfeld J; Diestel S (2012). UCHL1 regulates ubiquitination and recycling of the neural cell adhesion molecule NCAM. FEBS J. 279:4398-409.

3.      Zipser B; Bello-DeOcampo D; Diestel S; Tai M H; Schmitz B (2012). Mannitou monoclonal antibody uniquely recognizes paucimannose, a marker for human cancer, stemness and inflammation. J. Carbohydr. Chem. 31: 504-518.

4.      Marx M; Diestel S; Bozon M; Keglowich L; Drouot N; BouchéE; Frebourg T; Minz M; Saugier-Veber P; Castellani V; Schäfer M K E (2012). Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus. Neurogenetics, 13: 49-59.

5.      Schäfer M K E; Schmitz B; Diestel S (2010). L1 ubiquitination facilitates its lysosomal degradation. FEBS Lett., 584:4475-4480.

6.      Renker B; Diestel S; Ruonala M; Bertram J (2010). MATra – ein trojanisches Pferd für eine zellschonende Transfektion. BIOspektrum, 04/10:441-442.

7.      Boutin C; Schmitz B; Cremer H; Diestel S (2009). NCAM expression induces neurogenesis in vivo. Eur. J. Neurosci., 30:1209-1218.

8.      Boutin C; Diestel S; Desoeuvre A; Tiveron M C; Cremer H (2008). Highly efficient electroporation of the postnatal forebrain. PloS One, 3:e1883.

9.      Diestel S; Schaefer D; Cremer H; Schmitz B (2007). NCAM is ubiquitylated, endocytosed and recycled in neurons. J. Cell Sci., 120:4035-4049.

10. Schultheis M; Diestel S; Schmitz B (2007). The role of cytoplasmic serine residues of L1 in neurite outgrowth, endocytosis and cell migration. Cell. Mol. Neurobiol., 27:11-31.

11. Hinkle C L; Diestel S; Lieberman J; Maness P F (2006). Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM). J. Neurobiol., 66:1378-1395.

12. Diestel S; Hinkle C L; Schmitz B; Maness P F (2005). NCAM140 stimulates integrin-dependent cell migration by ectodomain shedding. J. Neurochem., 95:1777-1784.

13. Diestel S; Laurini C; Traub O; Schmitz B (2004). Tyrosine 734 of NCAM180 interferes with the FGF receptor-dependent signaling implicated in neurite growth. Biochem. Biophys. Res. Com., 322:186-196.

14. Diestel S; Eckert R; Hülser D; Traub O (2004). Exchange of serine residues 263 and 266 reduces the function of mouse gap junction protein Connexin31 and exhibits a dominant-negative effect on the wild type protein in HeLa cells. Exp. Cell Res., 294:446-457.

15. Diestel S; Richard G; Döring B; Traub O (2002). Expression of a connexin31 mutation causing Erythrokeratodermia variabilis is lethal for HeLa cells. Biochem. Biophys. Res. Commun., 296: 721-728

16. Traub O; Diestel S; Nam S W (2002). Kaloderma oder Keratoderma? Bioforum, Sonderausgabe “Zellbiologie”:26-28.

17. Wenzel U; Kuntz S; Diestel S; Daniel H (2002). PEPT1-mediated cefixime uptake into human intestinal epithelial cells is increased by Ca²⁺-channel blockers. Antimicrob. Agents and Chemother., 46:1375-1380.

18. Wenzel U; Diestel S; Daniel H (1998). Welche Rolle spielt der intestinale Peptidtransporter für die orale Verfügbarkeit anionischer und zwitterionischer beta-Lactamantibiotika. Zeitschrift für Gastroenterologie, Suppl. 1:24-28.

Laboratory assistants
Christine Laurini

Phone: +49-228 73 2067
Fax: +49-228 73 2024
Email: claurini@uni-bonn.de

Hedda von Quistorp

Email: h.quistorp@uni-bonn.de

Student Assistants

Mirka Homrich
Ms. Homrich supports the class "Spezielle Biochemie" (MA-H-08) as a student assistant.

Students
Master of Science students
Mirka Homrich
Ms. Homrich identifies and characterises novel interaction partners of the neuronal cell adhesion molecule NCAM and investigates their physiological relevance.

Bachelor of Science students
Dilek Eren
Ms. Eren writes about the potential of curcuminoids as chemopreventive dietary factors in the context of colorectal carcinoma.

Sina Maus
Ms. Maus reviews the health-beneficial properties of alkylresorcinols.

Ricarda Münch
Ms. Münch reviews the importance of the alpha-tocopherol transfer protein for the discrimination between the different vitamin E congeners.
Principal Investigator
Professor Jan Frank, Ph.D.
Phone: +49 711 459 24459
Fax: +49 711 459 24540
Email: jan.frank@nutrition-research.de

Curriculum vitae

EDUCATION

August 2004 - Ph.D. in Food Science, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden

September 2000 - Diploma (“Master of Science”) in Human Nutrition and Home Economics (“Diplom Oecotrophologe”), Bonn University, Germany

PROFESSIONAL EXPERIENCE

September 2012-present - Professor of Human Metabolomics, Department of Nutrition and Food Science, University of Bonn, Germany
September 2009-August 2012 - Group Leader (Bioavailability and Bioactivity of Micronutrients), Institute of Biological Chemistry and Nutrition, Hohenheim University, Stuttgart, Germany

June 2006 - Guest researcher, School of Biomedical and MolecularSciences, University of Surrey, Guildford, UK

March-May 2006 - Guest researcher, Hugh Sinclair Human Nutrition Group, School of Food Biosciences, University of Reading, UK

March 2005-August 2009 - Senior Researcher, Institute of Human Nutrition and Food Science, Christian Albrechts University (CAU), Kiel, Germany

August 2004-February 2005 - Postdoctoral researcher, Department of Food Science, SLU, Uppsala, Sweden

May-September 2003 - Collaborative research with Prof. Traber at the Linus Pauling Institute, Oregon State University, Corvallis, OR,USA

February 2001-July 2004 - Ph.D. student, Department of Food Science, SLU

October 2000-January 2001 - Guest researcher, Department of Food Science, SLU

July 1997-September 1998 - Guest student, research project at the Department of Food Science, SLU

October 1993-September 2000 - Student of Human Nutrition and Home Economics (“Ernährungs- und Haushaltswissenschaften”) a the University of Bonn, Germany

Memberships

Editorial Boards

Plant Foods for Human Nutrition (Springer)
since 2011
Co-Editor Europe for Nutrition (Elsevier)
since 2012
BioFactors (Wiley)
since 2013
Editor for Metabolism and Nutrition in Oncology (Thieme)
since 2013

Professional Societies

Deutsche Gesellschaft für Ernährung e.V. (German Nutrition Society)
since 1996

Oxygen Club of California
since 2002

New York Academy of Sciences
since 2004

NuGO - The European Nutrigenomics Organisation
since 2007

Society for Free Radical Research - Europe
since 2009

Gesellschaft für angewandte Vitaminforschung e.V.
since 2009, Member of the Board of Directors since 2012

Universitätsbund Hohenheim e.V.
since 2009

Life Science Center at the University of Hohenheim
since 2010
Food Security Center
since 2011

Voluntary Organisations

Bridge To Africa (BTA)
since 2008

On-call scientist for the AAAS Science and Human Rights Program
since 2008

Ph.D. Students
Christina Schiborr, M.Sc. Human Nutrition

Phone: +49 711 459 23115 or 23609
Email: christina.schiborr@nutrition-research.de

Christina developed an HPLC method for the quantification of curcumin in biological matrices during her MSc project at the University of Kiel, for which she was awarded the Helmut Erbersdobler Prize 2009. Christina's Ph.D. research deals with the modulation of the oral bioavailability of nutraceuticals.

Alexa Kocher, Diploma (M.Sc.) in Human Nutrition

Phone: +49 711 459 23115 or 23609
Email: alexa.kocher@nutrition-research.de

Alexa studies novel strategies to improve the oral bioavailability and the biological activities of health beneficial nutraceuticals in selected animal models and human intervention trials.

Maren Podszun, Diploma (M.Sc.) in Human Nutrition

Phone: +49 711 459 23115
Email: maren.podszun@nutrition-research.de
Maren Podszun studies the biological activities of vitamin E congeners and potential interactions of the vitamin with drugs.

Laboratory Assistants
Nadine Grebenstein, BTA

Phone: +49 711 459 23115
Email: nadine.grebenstein@nutrition-research.de

Nadine is the moving spirit of the group and takes care of our knockout mouse colony and cell culture facilities and performs biomolecular experiments as well as HPLC analyses.

Jochen Gogol, Ph.D.
Phone: +49 711 459 23609
Email: jochen.gogol@nutrition-research.de
Dr. Gogol performs experiments with transfected and normal cell lines to study the role of intracellular proteins in the trafficking and metabolism of micronutrients.

Student assistants

Verena Hörz
Verena Hörz supports the group by analysing different vitamin E-congeners and their metabolites by HPLC.

Eva-Marie Ziegler
Eva-Maria Ziegler helps with the extraction and quantification of curcumin and its metabolites by HPLC.

Students
Master of Science students
Ebru Erol
Ebru Erol investigates the antiproliferative effects of alkylresorcinols in cultured cancer cells and their metabolism in human hepatocytes.

Alumni
Former members of the group in Hohenheim.

Former Postdocs

Dr. Antonio Lama Muñoz
Dr. Antonio Lama Muñoz holds a Ph.D. in food science and was a visiting postdoctoral fellow from the Department of Food Biotechnology of the Spanish National Research Council. During his 3-month stay at Hohenheim, he investigated the impact of selected olive oil phytochemicals on the metabolism and inflammatory processes in liver cells.

Former Ph.D. Students

Surat Hongsibsong, M.Sc. Health Sciences
Surat was a visiting Ph.D. student from the Research Institute for Health Sciences at Chiang Mai University (Thailand) and funded by a scholarship from the Food Security Center. During his 6-months stay at Hohenheim, Surat investigated the impact of dietary factors on pyrethroid-induced oxidative stress.

Former Diploma Students

2012
Anne Senf
Anne Senf investigates the bioavailability of different curcumin formulations in humans.

2011

Maren Podszun

Maren Podszun studied potential nutrient-drug interactions of antioxidant vitamins with commonly prescribed drugs.

Kristina Seibold

Kristina Seibold studied the immuno-modulatory effects of selected phytochemicals in different organs in a model of accelerated aging.

2010
Dorothea Schwamm
Dorothea Schwamm investigated the effects of long-term consumption of dietary polyphenols on biomarkers of antioxidant status and inflammation in the heart in a model of accelerated aging. A part of her data was published in the scientific journal Current Pharmaceutical Biotechnology (see also publication no. 25).

Former Master of Science Students

2012

Sebastian Grashorn
Sebastian Grashorn studied the trafficking, sorting, and metabolism of vitamin E congeners in liver cells.

Sabrina Wiesner
Sabrina Wiesner studied interactions between curcumin and selected phytochemicals in the liver in mice and in hepatic cells in culture.

Janina Engstler
Janina Engstler studied interactions between curcumin and selected phytochemicals in the intestine using an in vivo model and in vitro cell culture experiments.

Mashaal Raza
Mashaal Raza studied the interactions of hypocholesterolemic drugs with dietary antioxidants in the context of non-alcoholic fatty liver disease.

Yu Zhuang
Yu Zhuang investigated the potential prevention of drug-induced muscle damage by simultaneous ingestion of antioxidants.

Former Bachelor of Science Students

Laura Eberhardt
Laura Eberhardt optimized a method for the determination of the antioxidant activity of cereal products and developed and validated a method for the quantification of tocopherols and tocotrienols by high-performance liquid chromatography with coulometric electrochemical array detection.

Anna Reeder
Anna Reeder studied the importance of the α-tocopherol-transfer protein and tocopherol-ω-hydroxylase activity for the biological activities of different vitamin E congeners in liver cell cultures.
Stefanie Schwab
Stefanie Schwab investigated potential synergistic interactions of selected phytochemicals with curcumin in a mouse model.
Juliane Schwaderer
Juliane Schwaderer studied the impact of simultaneously ingested plant extracts on the anti-inflammatory activity of curcumin in a mouse model.
Daniela Sommer
Daniela Sommer investigated the impact of dietary plant extracts on vitamin E metabolism in HepG2 cells.
Ina Feldhoffer
Ina Feldhoffer wrote about the age-dependent changes in the physiology of the heart muscle and potential beneficial effects of dietary phytochemicals.
Alena Hander
Alena Hander reviewed the current scientific evidence regarding the use of curcuminoids in the prevention and treatment of the mammary carcinoma.
Myriam Liegl
Myriam Liegl described the importance of hepatic proteins for the metabolism and biological activity of tocopherols and tocotrienols.

Former Interns and Student Assistants

Sebastian Grashorn
Sebastian Grashorn studied the uptake and metabolism of different vitamin E congeners and the cytotoxic effects of different curcumin formulations in Huh-7 liver cell cultures.

Katrin Kramer
Katrin Kramer studied the uptake kinetics of different vitamin E congeners in liver cell cultures.

Dominik Stammler

Dominik supported our team and helped determining enzyme activities and protein expression.

Former Laboratory Assistants

Emanuela Burchi, BTA

Emanuela oversaw our human and animal trials and performed biomolecular experiments as well as chemical analyses.

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