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Research

Jansen Lab

Table of Contents

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Research in the Jansen Laboratory focuses on the structure, function and pharmacology of membrane transport proteins. Our primary focus is neurotransmitter receptors of the pentameric ligand-gated ion channel superfamily (nAChR, 5-HT3 and GABA). We also investigate the proton-coupled folate transporter (PCFT), which mediates folate and antifolate uptake into tumors and cancer cells. The proteins we study represent therapeutic targets for neurological disorders and diseases, as well as cancer chemotherapy.

Read a recent News and Views feature in Nature by Dr. Jansen

Our research applies techniques from molecular biology (genetic engineering), biochemistry, chemical biology, biophysics (electrophysiology, spectroscopy and X-ray crystallography) and pharmacology.

Funding

Current and past funding from the following sources is gratefully acknowledged:

Research & Publications

Complete List of Publications
Complete List of Publications

  • Michaela Jansen's primary research focus are structure-function studies of membrane proteins on a molecular level. Additionally, we investigate mechanisms of drugs in current clinical use.

    Methods used include a wide array of molecular biology (protein engineering), biochemical and biophysical (X-ray crystallography, electrophysiology) as well as chemical biology and pharmacology approaches .

    One main focus are the so called Cys Loop receptors. These receptors function as neurotransmitter receptors. They transform the chemical signal contained in the neurotransmitter into an electrical signal. The superfamily of Cys Loop receptors has a variety of members, that are named after the ligand that opens (gates) them. They are virtually abundant in the central and peripheral nervous system and our research is therefore considered Neuroscience.

    These receptors were also identified in prokaryotes and we were the first lab to engineer functional chimeras by adding the intracellular domain that is only found in eukaryotic receptors to the proton-gated channel from Gloeobacter violaceus (GLIC).

    Receptor: Ligand: Clinically targeted for:
    nAChR Acetylcholine Treatment of Nicotine addiction, Alzheimer's Disease
    GABAA Gamma-aminobutyric acid Treatment of Epilepsy, Anaesthesia, Muscle relaxation, Anxiolytics
    5-HT3A 5-hydroxytryptamine = serotonin Treatment of Depression, Nausea in Chemotherapy

    Other members of the superfamily include receptors for glycine, zinc, glutamate, and protons. Each receptor is made up of five subunits that are arranged pseudosymmetrically around the central ion-conducting pore. These subunits can change their conformation from closed (non ion conducting) to open (ion conducting) states.

    The overall topology of the individual subunits is comparable. The ~200 amino acid long extracellular domain (ECD) harbors the ligand binding domain and the eponymous 13 amino acids bridging disulfide loop. Four alpha-helical segments (M1-M4) form the transmembrane domain (TMD). Two short loops, one intracellular between M1 and M2 and one extracellular between M2 and M3 connect the transmembrane segments. The large M3M4 loop is the major contributor to the intracellular domain (ICD). The intracellular domain is reduced to a minimum in prokaryotic Cys Loop Receptors.

    We were the first to show that the long M3M4 loop in 5HT3A and GABA rho1 can be replaced by just a heptapeptide linker (SQPARAA) from a prokaryotic homologue (GLIC) while retaining functionality.

    We have also generated the opposite chimeras between ECD and TMD of GLIC and diverse eukaryotic ICDs with the goal of further studying the structure and function of the ICD. 

    More recently, we have added ICDs to the soluble Maltose Binding Protein (MBP). We have found that the ICD itself drives pentamerization. 

  • Hoa Quynh Do, Michaela Jansen. (2022) Cell-Free Expression of Proton-Coupled Folate Transporter in the Presence of Nanodiscs. Methods in Mol. Biol., 2507:425-444. PMID: 35773596.

    Hoa Quynh Do, Carla M Bassil, Elizabeth I Andersen, Michaela Jansen (2021). Impact of nanodisc lipid composition on cell-free expression of proton-coupled folate transporter. PLoS One 2021 Nov 18;16(11):e0253184. PMCID: PMC8601550. DOI: 10.1371/journal.pone.0253184

    Antonia G. Stuebler, Michaela Jansen (2020). Mobility of Lower MA-Helices for Ion Conduction through Lateral Portals in 5-HT 3A Receptors. Biophys J. 119 (12), 2593-2603. PMID: 33157122  PMCID: PMC7822733

    Antonia G. Stuebler, Michaela Jansen (2020). Bupropion Inhibits Serotonin Type 3AB Heteromeric Channels at Clinically Relevant Concentrations. Mol Pharm. 97 (3) 171-179. PMID: 31871303

    Elham Pirayesh, Akash Pandhare, Antonia G. Stuebler, Michaela Jansen (2020). Delineating the Site of Interaction of the 5-HT3A Receptor with the Chaperone Protein RIC-3. Biophys J. Epub ahead of print. PMID: 31870537

    Akash Pandhare, Elham Pirayesh, Antonia G. Stuebler, Michaela Jansen (2019). Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HT3A receptors. J Gen Physiol. 151 (9), 1135-1145.

    Michaela Jansen (2019). An in-depth structural view of a GABAA brain receptor. Nature. Epub 2019 Jan 02.

    Akash Pandhare, Antonia G Stuebler, Elham Pirayesh, Michaela Jansen (2019). A modified clear-native polyacrylamide gel electrophoresis technique to investigate the oligomeric state of MBP-5-HT3A-intracellular domain chimeras. Protein Expression and Purification. 153, 45-52.

    Swapneeta S. Date, Mariana C. Fiori, Guillermo A. Altenberg, Michaela Jansen  (2017). Expression in Sf9 insect cells, purification and functional reconstitution of the human proton-coupled folate transporter (PCFT, SLC46A1) PLOS One. 12(5):e0177572

    Akash Pandhare, Aneesh Satya Pappu, Henrik Wilms, Michael Paul Blanton, Michaela Jansen (2017).  The antidepressant bupropion is a negative allosteric modulator of serotonin type 3A receptors. Neuropharmacology. 113(Pt A):89-99.

    Akash Pandhare, Petar N. Grozdanov & Michaela Jansen (2016). Pentameric quaternary structure of the intracellular domain of serotonin type 3A receptors. Sci Rep. 6. 6:23921.

    Sita Nirupama Nishtala, Nelli Mnatsakanyan, Akash Pandhare, Chun Leung, Michaela Jansen (2016). Direct interaction of the resistance to inhibitors of cholinesterase type 3 protein with the serotonin receptor type 3A intracellular domain. J Neurochem. 137(4):528-38.

    Swapneeta S. Date, Cheng‐Yen Charles Chen, Yidong Chen, Michaela Jansen (2016). Experimentally optimized threading structures of the proton‐coupled folate transporter. FEBS Open Bio. 6(3):216-30.

    Nelli Mnatsakanyan, S Nirupama Nishtala, Akash Pandhare, Mariana C Fiori, Raman Goyal, Jonathan E Pauwels, Andrew F Navetta,  Afzal Ahrorov, Jansen M (2015). Functional Chimeras of GLIC Obtained by Adding the Intracellular Domain of Anion- and Cation-Conducting Cys-loop Receptors. Biochemistry. 54(16):2670-2682. 

    Phaneendra Kumar Duddempudi, Raman Goyal, Swapneeta Sanjay Date, Michaela Jansen (2013). Delineating the Extracellular Water-Accessible Surface of the Proton-Coupled Folate Transporter. PLOS One. 8(10):e78301

    Phaneendra K. Duddempudi, Prachi Nakashe, Michael P. Blanton, Michaela Jansen (2013). The monomeric state of the proton‐coupled folate transporter represents the functional unit in the plasma membrane. The FEBS Journal. 280(12):2900-15.

    Nelli Mnatsakanyan, Michaela Jansen (2013). Experimental determination of the vertical alignment between the second and third transmembrane segments of muscle nicotinic acetylcholine receptors. Journal Neurochem. 25(6):843-54.

    Jonathan M. Labriola, Akash Pandhare, Michaela Jansen, Michael P. Blanton, Pierre-Jean Corringer, John E. Baenziger (2013). Structural sensitivity of a prokaryotic pentameric ligand-gated ion channel to its membrane environment. J Biol Chem 288(16):11294-303.

    Akash Pandhare, Ayman K. Hamouda, Brandon Staggs, Shaili Aggarwal, Phaneendra K. Duddempudi, John R. Lever, David J. Lapinsky, Michaela Jansen, Jonathan B. Cohen, Michael P. Blanton (2012). Bupropion Binds to Two Sites in the Torpedo Nicotinic Acetylcholine Receptor Transmembrane Domain: A Photoaffinity Labeling Study with the Bupropion Analogue [125I]-SADU-3-72. Biochemistry. 51(12):2425-35.

    Raman Goyal, Ahmed Abdullah Salahudeen, Michaela Jansen (2011). Engineering a Prokaryotic Cys-loop Receptor with a Third Functional Domain. J Biol Chem. 286(40):34635-42.

    A. Bauman, M. Piel, S. Höhnemann, A. Krauss, Michaela Jansen, C. Solbach, G. Dannhardt,b and F. Rösch (2010). Synthesis, labelling and evaluation of hydantoin‐substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N‐methyl‐D‐aspartate receptor. J Label Compd Radiopharm. 54(10):645-656.

    Moez Bali, Michaela Jansen and Myles H. Akabas (2009). GABA-Induced Intersubunit Conformational Movement in the GABAA Receptor α1M1-β2M3 Transmembrane Subunit Interface: Experimental Basis for Homology Modeling of an Intravenous Anesthetic Binding Site. J Neurosci.29 (10) 3083-3092.

    Roger Ernest Wiltfong and Michaela Jansen (2009). Probing Protein Packing Surrounding the Residues in and Flanking the Nicotinic Acetylcholine Receptor M2M3 Loop. J Neuroscience. 29(6):1626 –1635.

    Michaela Jansen, Holger Rabe, Axelle Strehle, Sandra Dieler, Fabian Debus, Gerd Dannhardt, Myles H. Akabas, and Hartmut Luddens (2007). Synthesis of GABAA Receptor Agonists and Evaluation of their α-Subunit Selectivity and Orientation in the GABA Binding Site. J Med Chem. 51(15):4430-48

    Rongbao Zhao, Andong Qiu, Eugenia Tsai, Michaela Jansen, Myles H. Akabas, and I. David Goldman (2008). The Proton-Coupled Folate Transporter: Impact on Pemetrexed Transport and on Antifolates Activities Compared with the Reduced Folate Carrier. Mol Pharmacol. 74(3):854-62.

    Michaela Jansen , Moez Bali , and Myles H. Akabas (2008). Modular Design of Cys-loop Ligand-gated Ion Channels: Functional 5-HT 3 and GABA 1 Receptors Lacking the Large Cytoplasmic M3M4 Loop. J. Gen. Physiol. 131: 137–146.

    Andong Qiu, Sang Hee Min, Michaela Jansen, Usha Malhotra, Eugenia Tsai, Diane C. Cabelof, Larry H. Matherly, Rongbao Zhao, Myles H. Akabas, and I. David Goldman (2007). Rodent intestinal folate transporters (SLC46A1): secondary structure, functional properties, and response to dietary folate restriction. Am J Physiol Cell Physiol. 293: C1669–C1678.

    Andong Qiu, Michaela Jansen, Antoinette Sakaris, Sang Hee Min, Shrikanta Chattopadhyay, Eugenia Tsai, Claudio Sandoval, Rongbao Zhao, Myles H. Akabas, and I. David Goldman (2006). Identification of an Intestinal Folate Transporter and the Molecular Basis for Hereditary Folate Malabsorption. Cell. 127(5):917-28.

    Michaela Jansen and Myles H. Akabas (2006). State-Dependent Cross-Linking of the M2 and M3 Segments: Functional Basis for the Alignment of GABAA and Acetylcholine Receptor M3 Segments. J Neurosci. 26(17):4492– 4499.

    David C. Reeves, Michaela Jansen, Moez Bali, Thomas Lemster, and Myles H. Akabas (2005). A Role for the 1 – 2 Loop in the Gating of 5-HT3 Receptors. J Neurosci. 25(41):9358 –9366. 

Meet Our Team

  • Current lab member information will be added as it becomes available.

  • The following information is presented in the format:

    Name / Time in Lab / Position Afterwards

    See where some of our former lab members continued their careers:

    • Chris Hornback, 2019 to 2020
    • Trevor Anderson, 2016 to 2017, TTUHSC Medical Student, Laboratory Internship during leave of absence.
    • Oscar Wu, 2016 to 2017, Lab Volunteer, TTU, Lubbock.
    • Nanh Phan, 2015 to 2016, Technician, UT Southwestern, Dallas, TX
    • Dakota Kilcrease, 2015 to 2016, CISER/SSO Honors Student Lab Intern, TTU, Lubbock.
    • Akash Pandhare, 2014 to 2019, Johnson & Johnson.
    • Afzal Ahrorov, 2012 to 2013, HHMI Program, TTU, TX. Subsequently Graduate School at the University of Houston (started 2013), Cell and Molecular Biology, specializing in Cancer Biology, Houston, TX.
    • Nelli Mnatsakanyan, 2011 to 2014, Associate Research Scientist at Yale University, New Haven, CT
    • Raman Goyal, 2009 to 2012, Lab Manager, Duke University Medical Center, Durham, NC. Physiology Graduate Student, UC Davis after 2014
    • Gautham Brahmamudi, 2009 to 2010, Manager, Technology Transfer, Center for Innovation, Arlington, TX
    • Jessica Shepherd, 2019, TTUHSC Medical Student Summer Research Program.
    • Dubem Onyejegbu, 2019, TTUHSC Medical Student Summer Research Program.
    • Felix Omoruyi, 2018, TTUHSC Medical Student Summer Research Program.
    • Mina Ahmadi, 2017, PhD. Chemistry, U Minnesota, MN
    • Ali Ahmed, 2017, TTUHSC Medical Student Summer Research Program.
    • Jack Littlejohn, 2017, TTUHSC Medical Student Summer Research Program.
    • Carla Bassil, 2017, TTU Clark Scholar, TX.
    • Swapneeta Date, 2016, Postdoc Oakridge National Laboratory, Oak Ridge, TN
    • Elham Pirayesh, 2016, GSBS PhD, Lubbock, TX
    • Joseph D. Witt, 2016, TTUHSC Medical Student Summer Research Program.
    • Michael A. Strong, 2016, TTUHSC Medical Student Summer Research Program.
    • Grace Shim, 2016, TTUHSC Medical Student, Laboratory Internship.
    • Daniel Cherkowsky, 2016, Lab Volunteer, TTU, Lubbock.
    • S Nirupama Nishtala, 2015, Postdoc at Einstein, New York, NY
    • S Nirupama Nishtala, 2015, Postdoc at Einstein, New York, NY
    • Laura Delin, 2015, TTUHSC Medical Student Summer Research Program. Currently in the 2nd year of medical school.
    • Chun (Frankie) Leung, 2015, TTUHSC Medical Student Summer Research Program
    • Chun (Frankie) Leung, 2015, TTUHSC Medical Student, Laboratory Internship during leave of absence.
    • Katherine Jenkins, 2015, TTUHSC Summer Accelerated Research Program (SABR), TTU, Lubbock.
    • Dominique Gagnon, 2014, Medical Student at TTUHSC SOM, Lubbock, TX
    • Jeremy Thompson, 2014, TTUHSC M.D.- Ph.D. Laboratory Rotation (07/2014-09/2014).
    • Cheng-Yen Charles Chen, 2014, TTUHSC Medical Student Summer Research Program. Residency started 2017, Univ of Oklahoma COM – Tulsa, Emergency Medicine.
    • Anna Sabrina Beroncal De Leon, 2014, Summer Accelerated Research Program (SABR).
    • Aneesh Pappu, 2014, TTU Clark Scholar, TX.
    • P Kumar Duddempudi, 2013, Postdoc Einstein, New York, NY
    • Yidong Chen, 2013, TTUHSC Medical Student Summer Research Program. Residency started 2016, York Hospital – PA, Emergency Medicine.
    • Jonathan E Pauwels, 2012, Research Assistant UT Southwestern, Dallas, TX
    • Tereza Tomankova, 2012, TTUHSC Summer Accelerated Research Program (SABR), Muskingum University, OH. Subsequently Medical School in Prague (started 2013), Czech Republic.
    • Robin Rajan, 2011, Research Associate, SOP, Abilene, TX
    • Andrew Frank Navetta, 2011, TTUHSC Medical Student Summer Research Program. Residency started 2014, Surgery Preliminary / Urology Residency Program, Texas A&M – Scott & White, Temple, TX.
    • Zoltan Krudy, 2011, TTUHSC Summer Accelerated Research Program (SABR), TTU, TX. Admitted to Paul Foster School of Medicine (to start 2014), El Paso, TX.
    • Prachi Nakashe, 2010, Research Associate Bioo Scientific, Austin, TX
    • Ahmed Abdullah Salahudeen, 2010, TTUHSC Medical Student Summer Research Program. Residency started 2013, Internal Medicine Residency Program, University of Texas Medical School, Houston, TX.
    • Valentina Snetkova, 2010, TTUHSC Summer Accelerated Research Program (SABR), Jacobs-University, Germany. Subsequently Biomedical Sciences (Stem Cells Track) Graduate Program at NYU School of Medicine, NY.
    • Juan Ortega, 2010, TTU Plains Bridges to the Baccalaureate Program, South Plains College, Levelland, TX.
    • Dane Langsjoen, 2009, TTUHSC Medical Student Summer Research Program. Resident started 2012, Internal Medicine Residency Program, Texas A&M – Scott & White, Temple, TX.
    • Camille Perot, 2009, TTUHSC Summer Accelerated Research Program (SABR), Université de Poitiers, Poitiers, France.
    • Ruth D’Cunha, 2009, TTU Clark Scholar, TX.

Leadership

Michaela Jansen

Associate Dean of Curriculum, Director of Assessment, Professor, Clinical Professor HSC