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Michael T. Klein, Ph.D.

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<strong>Michael</strong> T. <strong>Klein</strong>, <strong>Ph</strong>.D.<br />

Vanderbilt University Medical Center<br />

Vanderbilt Center for Neuroscience Drug Discovery<br />

1215 Light Hall<br />

Nashville, TN 37232-0697<br />

<strong>Ph</strong>one: (518) 763-2807<br />

Fax: (615) 343-3088<br />

Email: <strong>Michael</strong>.T.<strong>Klein</strong>@vanderbilt.edu<br />

Professional experience<br />

Postdoctoral Research Fellow (September 2012 – present)<br />

Laboratory of Prof. P. Jeffery Conn, Department of <strong>Ph</strong>armacology, Vanderbilt University Medical Center,<br />

Nashville, TN, USA.<br />

Investigating allosteric modulation of muscarinic acetylcholine receptors.<br />

Research Assistant (May 2006 - July 2006)<br />

Under supervision of Prof. Mario Canki, Center for Immunology and Microbial Disease, Albany Medical<br />

College, Union University, Albany, NY, USA.<br />

Investigated novel anti-viral compounds for the treatment and prevention of HIV infection.<br />

Education<br />

Doctor of <strong>Ph</strong>ilosophy awarded in Neuropharmacology & Neuroscience (2011) from Albany Medical<br />

College, Union University, GPA 3.70<br />

Dissertation research supervised by Prof. Milt Teitler, “The <strong>Ph</strong>armacology and Distribution of Serotonin<br />

5-HT1E Receptors in the Mammalian Brain & Drug Development for the Human 5-HT1E Receptor”<br />

Bachelors of Science awarded in Biochemistry and Molecular Biology (2006), University at Albany, State<br />

University of New York, GPA 3.70<br />

Senior undergraduate research project supervised by Prof. Mario Canki, “HIV-1 Modulation of SP-1, Oct-<br />

1, and NFκB Transcription Factor Expression in Human Fetal Astrocytes”<br />

Research experience<br />

<strong>Ph</strong>.D. dissertation research:<br />

■ Identified the distribution of serotonin 5-HT1E receptors in the mammalian brain, identified cell<br />

types that express 5-HT1E receptors, established rational for future electrophysiological and<br />

behavioral analyses of 5-HT1E receptor function in the mammalian brain, and provided evidence to<br />

support the 5-HT1E receptor as a potential therapeutic target for the treatment of disorders<br />

characterized by cognitive and memory deficits (<strong>Klein</strong> and Teitler, in press).<br />

■ 5-HT1E receptor drug discovery: determined affinities of 52 compounds and the functional<br />

potencies of a subset of these compounds at h5-HT1E and h5-HT1F receptors to establish a<br />

comparative SAR and identify new avenues for subtype-selective drug discovery at 5-HT1E and 5-<br />

HT1F receptors (<strong>Klein</strong> et al., 2011).


■ <strong>Ph</strong>armacologically characterized 5-HT1E receptors expressed in guinea pig brain tissue and<br />

demonstrated the utility of the guinea pig as the first pre-clinical animal model for the study of 5-<br />

HT1E receptors and drug screening (<strong>Klein</strong> and Teitler, 2009).<br />

Other graduate level research:<br />

■ Identified novel drug-induced inactivation and reactivation properties of 5-HT2A receptor<br />

homodimers and developed new equations to model these novel ligand-receptor interactions<br />

(Teitler and <strong>Klein</strong>, 2011).<br />

■ Identified and characterized drug-induced inactivation and reactivation of 5-HT7 homodimers<br />

heterologously expressed in recombinant cell lines (Teitler et al., 2010) and endogenously<br />

expressed in primary rat astrocytes (Smith et al., 2010).<br />

■ Identified and characterized novel forskolin-inhibiting effects of 5-HT7 receptor competitive<br />

antagonists (<strong>Klein</strong> and Teitler, 2011) and “inactivating” antagonists (Toohey et al., 2009).<br />

■ Examined the novel, rapid, and potent pseudo-irreversible inhibition of 5-HT7 receptors by<br />

“inactivating” antagonists (Knight et al., 2009).<br />

■ Designed FRET-paired 5-HT receptors to visualize receptor dimerization under confocal<br />

microscopy. Characterized 5-HT2C receptor homodimer interface via mutagenesis of key residues of<br />

receptor transmembrane domains (poster 44.9 at Sf N meeting, Nov 2006).<br />

■ Investigated the novel cytochrome P450-activating properties of the analgesic improgan as an<br />

underlying mechanism of improgan’s nociceptive properties.<br />

Undergraduate research:<br />

■ Identified compounds and natural products with ability to inhibit HIV infection in recombinant cell<br />

lines and human fetal astrocytes. Determined cytotoxicity of these compounds (Paskaleva et al.,<br />

2006).<br />

■ Examined the HIV viral lifecycle in human fetal astrocytes and monitored changes in transcription<br />

factors to develop a novel in vitro model for AIDS-associated dementia.<br />

Skills and expertise<br />

■ <strong>Ph</strong>armacology: autoradiography, radioligand binding, quantification of second messengers (cAMP,<br />

inositol phosphates), Ca 2+ mobilization, non-radioactive binding assays (DELFIA), gene-reporter<br />

assays (luciferase and β- galactosidase), receptor operational modeling, cytotoxicity screening.<br />

■ Molecular biology: DNA amplification and purification, restriction digest and ligation, agarose gel<br />

electrophoresis, PCR, PCR-based mutagenesis, RT-PCR, viron production and quantification.<br />

■ Immunochemical techniques: immunocytochemistry, immunohistochemistry, Western blot, ELISA,<br />

polyacrylamide gel electrophoresis.<br />

■ Biophysical techniques: resonance energy transfer, design of FRET and BRET assays, enzyme<br />

complementation, fluorescence complementation, fluorescence polarization, time-resolved<br />

fluorescence.


■ Cell culture: recombinant cell line culture (HEK-293, 293t, CHO, CHO-K1, COS-7, HeLa, LMtk-, 1G5,<br />

U-373), primary lymphocyte culture, primary astrocyte culture, mammalian cell transfection,<br />

monoclonal cell line production.<br />

■ Microscopy: confocal microscopy, wide-field fluorescence microscopy.<br />

■ Animal handling and tissue preparation: rodent euthanasia, rodent brain dissection, microtome<br />

and cryostat tissue sectioning, paraformaldehyde tissue fixation, tissue cryoprotection.<br />

■ Data processing and analysis: parametric and nonparametric statistical analyses, linear and<br />

nonlinear regression, design of custom nonlinear regression equations, MS Excel automated batch<br />

processing, GraphPad Prism automated batch processing, Adobe <strong>Ph</strong>otoshop automated batch<br />

processing.<br />

Graduate level coursework<br />

Behavioral Neuroscience, Biochemistry, Bioethics, Biostatistics, Cellular & Molecular Neuroscience,<br />

Fundamentals of <strong>Ph</strong>armacology, Molecular Cell Biology, Nervous System Disorders, Neuroanatomy,<br />

Neuroanatomy Lab, Neuropharmacology, Receptor <strong>Ph</strong>armacology, and Scientific Integrity (cumulative<br />

GPA 3.70).<br />

Supervision/teaching experience<br />

■ Responsible for training research assistant (Jeremy Teitler) and medical student investigator<br />

(Soma Mandal) in standard pharmacological, cell culture, and molecular biology techniques in the<br />

laboratory of Prof. Milt Teitler.<br />

■ Responsible for training of new users of departmental shared instruments.<br />

Awards and recognition<br />

■ Frank C. Ferguson Jr. Prize for Excellence in the Quality of Science (2011)<br />

■ Albany Medical College Research Poster Day Award (2011)<br />

■ Albany Medical College Alumni Association Research and Leadership Award (2011)<br />

■ New York State Merit-Academic Excellence Award<br />

■ International Brotherhood of Boilermakers Local 5 College Scholarship<br />

■ State University of New York at Albany Presidential Scholarship<br />

■ State University of New York at Albany College Scholarship<br />

Professional affiliations<br />

■ Member of American Society for <strong>Ph</strong>armacology and Experimental Therapeutics (ASPET)<br />

■ Member of the Society for Neuroscience (SfN)<br />

■ Member of the British <strong>Ph</strong>armacological Society


■ Member of the Serotonin Club<br />

Extracurricular responsibilities<br />

■ Student Council representative for the Center for Neuropharmacology & Neuroscience<br />

■ Treasurer of the Graduate Student Organization<br />

■ Graduate Student Organization representative for the Center for Neuropharmacology &<br />

Neuroscience<br />

■ Center for Neuropharmacology & Neuroscience Graduate Education Committee<br />

■ Albany Medical College Information Technology Advisory Committee (member)<br />

■ Biostatistics Curriculum and Course Restructuring Committee (member)<br />

■ Albany Medical College Website Committee (member)<br />

■ Center for Neuropharmacology & Neuroscience Platereader Committee (chair)<br />

Volunteer work<br />

■ Volunteer for Habitat for Humanity construction projects<br />

■ Member of the community service clubs Circle K and Presidential Honors Society<br />

■ Assistant at Albany’s New Day Art & Reading program for underprivileged children<br />

■ Volunteer at Albany Regional Food Bank<br />

■ Assisted in the care of Guiding Eyes for the Blind dogs<br />

■ Participated in Brittany Miller Foundation, Crop Walk, March of Dimes, and Make-a-Wish<br />

Foundation events<br />

Peer-reviewed publications<br />

<strong>Klein</strong> M.T. and Teitler M. (in press) Distribution of 5-HT1E receptors in the mammalian brain and cerebral<br />

vasculature: an immunohistochemical and pharmacological study. British Journal of<br />

<strong>Ph</strong>armacology.<br />

Teitler M. and <strong>Klein</strong> M.T. (2011) A new approach for studying GPCR dimers: drug-induced inactivation<br />

and reactivation to reveal GPCR dimer function in vitro and in vivo. <strong>Ph</strong>armacology &<br />

Therapeutics, Epub ahead of print. PMID: 22119169.<br />

<strong>Klein</strong> M.T., Dukat M., Glennon R.A., and Teitler M. (2011) Towards selective drug development for the<br />

human 5-HT1E receptor: a comparison of 5-HT1E and 5-HT1F receptor structure-affinity<br />

relationships. Journal of <strong>Ph</strong>armacology and Experimental Therapeutics, 337(3):860-867. PMID:<br />

21422162.<br />

<strong>Klein</strong> M.T. and Teitler M. (2011) Antagonist interaction with the human 5-HT7 receptor mediates the<br />

rapid and potent inhibition of non-G-protein-stimulated adenylate cyclase activity: a novel GPCR<br />

effect. British Journal of <strong>Ph</strong>armacology, 162(8):1843-1854. PMID: 21198551.


Smith C., Toohey N., <strong>Klein</strong> M.T., Knight J.A., and Teitler, M. (2010) Risperidone-induced inactivation and<br />

clozapine-induced re-activation of rat cortical astrocyte 5-HT7 receptors: evidence for in situ<br />

GPCR homodimer protomer cross-talk. Molecular <strong>Ph</strong>armacology, 79(2):318-325. PMID:<br />

21062995.<br />

Teitler M., Toohey N., Knight J.A., <strong>Klein</strong> M.T., and Smith C. (2010) Clozapine and other competitive<br />

antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and<br />

functional evidence for GPCR homodimer protomer interactions. Psychopharmacology (Berlin),<br />

212(4):687-697. PMID: 20827463.<br />

<strong>Klein</strong> M.T. and Teitler M. (2009) Guinea pig hippocampal 5-HT1E receptors: a tool for selective drug<br />

development. Journal of Neurochemistry, 109(1):268-274. PMID: 19200348.<br />

Toohey N., <strong>Klein</strong> M.T., Knight J.A., Smith C., and Teitler M. (2009) Human 5-HT7 receptor-induced<br />

inactivation of forskolin-stimulated adenylate cyclase by risperidone, 9-OH-risperidone and<br />

other “inactivating antagonists”. Molecular <strong>Ph</strong>armacology, 76(3):552-559. PMID: 19509219.<br />

Knight J.A., Smith C., Toohey N., <strong>Klein</strong> M.T., and Teitler M. (2009) <strong>Ph</strong>armacological analysis of the novel,<br />

rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-<br />

OH-risperidone, and other “inactivating antagonists”. Molecular <strong>Ph</strong>armacology, 75(2):374-380.<br />

PMID: 18996971.<br />

Paskaleva E.E., Lin X., Li W., Cotter R., <strong>Klein</strong> M.T., Roberge E., Yu E. K., Clark B., Veille J., Liu Y., Lee D.,<br />

and Canki M. (2006) Inhibition of highly productive HIV-1 infection in T cells, primary human<br />

macrophages, microglia, and astrocytes by Sargassum fusiforme. AIDS Research and Therapy,<br />

3:15. PMID: 16725040.<br />

Published abstracts and presentations at national meetings<br />

Teitler M., Smith C., Toohey N., and <strong>Klein</strong> M.T. “Fluphenazine potently and rapidly inactivates the<br />

human D2 dopamine receptor.” Poster 136.4 at Society for Neuroscience Annual Meeting,<br />

Washington D.C. November, 2011.<br />

<strong>Klein</strong> M.T. and Teitler M. “Serotonin 5-HT1E receptor distribution in the guinea pig brain: The first<br />

specific localization of 5-HT1E receptors in mammalian brain tissue.” Poster 543.5 at Society for<br />

Neuroscience Annual Meeting, San Diego, CA. November, 2010.<br />

Toohey N., Smith C., <strong>Klein</strong> M.T. and Teitler M. “Drug-induced inactivation and reactivation of the human<br />

5-HT2A receptor.” Poster 543.9 at Society for Neuroscience Annual Meeting, San Diego, CA.<br />

November, 2010.<br />

Knight J.A., Smith C., Toohey N., <strong>Klein</strong> M.T. and Teitler M. “Clozapine and other competitive antagonists<br />

reactivate risperidone-inactivated human and rat 5-HT7 receptors: functional evidence for a<br />

GPCR homodimer in cell lines and primary culture.” Poster 543.8 at Society for Neuroscience<br />

Annual Meeting, San Diego, CA. November, 2010.<br />

<strong>Klein</strong> M.T., Dukat M., Glennon R.A. and Teitler M. “Towards selective drug development for the human<br />

5-HT1E receptor: A comparative 5-HT1E/5-HT1F structure-affinity investigation.” Poster 35.12 at<br />

Society for Neuroscience Annual Meeting, Chicago, IL. October, 2009.<br />

<strong>Klein</strong> M.T., Toohey N., Smith C., Knight J.A. and Teitler M. “Human 5-HT7 receptor antagonist-elicited<br />

inhibition of forskolin-stimulated adenylate cyclase activity: A novel GPCR-mediated effect.”<br />

Poster 35.6 at Society for Neuroscience Annual Meeting, Chicago, IL. October, 2009.


<strong>Klein</strong> M.T. and Teitler M. “Guinea Pig Hippocampal 5-HT1E Receptors: A Tool for Selective Drug<br />

Development.” Poster 825.6 Society for Neuroscience Annual Meeting, Washington D.C.<br />

November, 2008.<br />

<strong>Klein</strong> M.T. and Teitler M. “Guinea Pig Hippocampal 5-HT1E Receptors: A Tool for Selective Drug<br />

Development.” Poster 720.8 at Experimental Biology (FASEB), San Diego, CA. April, 2008.<br />

Farrington D.T., Weaver B.A., Grinde E., <strong>Klein</strong> M.T. and Herrick-Davis K. “Structural determination of<br />

serotonin 5-HT2C receptor trafficking to the plasma membrane.” Poster 44.9 at Society for<br />

Neuroscience Annual Meeting, Atlanta, GA. November, 2006.

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