Ted Meigs, Ph.D.

GlaxoSmithKline Professor of Molecular and Chemical Biology

Contact Information

  • tmeigs@unca.edu
  • 828-232-5155
  • 305 Zeis Hall

Office Hours

  • Monday 8:15 am - 9:50 am
  • Friday 8:15 am - 9:50 am
  • Note:

 

Personal Statement

My research goals are to understand the signaling functions of the G12/13 class of trimeric G proteins, specifically the role of their interactions with numerous intracellular effector proteins, and the structural features that arose during evolution of this G protein class to allow engagement of specific pathways. I have worked in this field for 18 years, beginning with my post-doctoral studies with Pat Casey in which we identified one of the earliest binding partners of activated Gα12, the cadherin cytoplasmic tail.

In my position as a biology professor, I strive to be equal parts scientist and educator. UNC Asheville is the public liberal arts institution of the UNC system, and my laboratory is populated exclusively by undergraduate students. One of my everyday challenges is to provide intensive hands-on guidance to students in biological concepts and experimental techniques, while maintaining a relevant, productive, viable research program in a competitive field populated by labs of graduate students and post-docs. I train and guide my undergraduates in a variety of projects to elucidate structural determinants of different G12/13-effector interactions and link these to specific downstream responses in cells. These experiments require students to gain proficiency in PCR-based subcloning, design and execution of targeted mutagenesis, bacterial culture, affinity purification of plasmids and recombinant proteins, mammalian cell culture and transfections, cell fractionation, protein interaction assays, SDS-PAGE and immunoblotting, reporter gene assays, and quantitative and statistical analyses of data.

I recruit many of my students from courses I teach, in which I seek excellent academic performers who also show keen interest in scientific discovery and are reliable, punctual, and enthusiastic about bench work.  Projects typically span 12-24 months, and I involve these students in all aspects of the research, from reagent preparation to experimental design. I require them to give oral and written presentations of their work, both on- and off-campus. In a decade at UNC Asheville, I have mentored more than 45 students in my lab, and in 25 instances a student of mine has received co-authorship on a peer-reviewed publication. I have taken six groups of students to national scientific meetings, where these students have presented research posters and, in April 2014, a student received Honorable Mention at the American Society for Biochemistry and Molecular Biology (ASBMB undergraduate poster competition). As my students gain experience, they are increasingly given research goals and laboratory responsibilities more at a graduate school level. I feel one of my most important roles is to provide my students a level of preparation and rigor that will allow them to transition into graduate and professional programs with strong self-reliance, technical skill, knowledge of cell biology, and ability to manage complex problems and experimental systems.  Students whom I have mentored in undergraduate research have enrolled in Ph.D. programs at Johns Hopkins Univ., UNC-Chapel Hill, Brandeis, NYU, Univ. of Alberta, Univ. of Ala. Birmingham, and Univ. of California, Berkeley, plus medical schools (UNC-Chapel Hill, Univ. of New Mexico), veterinary schools (NC State Univ., Lincoln Memorial), pharmacy schools (UNC-Chapel Hill and East Tenn. St.), and dental school (UNC-Chapel Hill).

Education

  • Western Carolina University; B.S. in Biology (1990)
  • Stanford University; Ph.D. in Biological Sciences (1996)
  • Duke University Medical Center; Postdoc, Cancer Biology and Pharmacology (1996-2001)

Positions and Employment

  • 2001-2003: Research Scientist, Center for Chemical Biology, Duke University Medical Center
  • 2003-2009: Assistant Professor, Dept. of Biology, UNC Asheville
  • 2009-2015: Associate Professor of Biology with Tenure, UNC Asheville
  • 2011-pres.: GlaxoSmithKline Distinguished Professorship in Molecular and Chemical Biology, UNC Asheville
  • 2015-pres.:Professor of Biology, UNC Asheville

Awards and Fellowships

  • 1990: Outstanding Biology Senior Award, Western Carolina University
  • 1993: Centennial Graduate Assistant Teaching Award, Stanford University
  • 1996-1997: Duane Rodgers and John Moorish Memorial Research Fellowship
  • 1997-2000: National Research Service Award, National Institutes of Health
  • 2002: Alumni Award for Academic and Professional Achievement, W. Carolina Univ.
  • 2008: Scholarly and Creative Achievement Award, UNC Asheville
  • 2008: Award for Excellent Teaching by an Untenured Faculty Member, UNC Asheville
  • 2009-pres.: Affiliate Membership, UNC Lineberger Comprehensive Cancer Center
  • 2012: Alumni Distinguished Faculty Award, UNC Asheville
  • 2012: University Teacher of the Year Award, UNC Asheville

Peer-Reviewed Publications

1.   Coyle, F.A. and Meigs, T.E. (1989) Two new species of kleptoparasitic Mysmenopsis (Araneae, Mysmenidae) from Jamaica. J. Arachnol. 17: 59-70.

2.   Coyle, F.A. and Meigs., T.E. (1990) Two new species of Ischnothele funnelweb spiders (Araneae, Mygalomorphae, Dipluridae) from Jamaica. J. Arachnol. 18: 95-111.

3.   Coyle, F.A. and Meigs, T.E. (1992) Web co-habitants of the African funnelweb spider, Thelechoris  karschi (Araneae, Dipluridae). J. African Zool. 106: 289-295.

4.   Meigs, T.E. and Simoni, R.D. (1992) Regulated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in permeabilized cells. J. Biol. Chem. 267: 13547-13552.

5.   Meigs, T.E., Sherwood, S.W., and Simoni, R.D. (1995) Farnesyl acetate, a derivative of an isoprenoid of the mevalonate pathway, inhibits DNA replication in hamster and human cells. Exp. Cell Res. 219: 461-470.

6.   Meigs, T.E., Roseman, D.S. and Simoni, R.D. (1996) Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase turnover by a nonsterol mevalonate metabolite in vivo.  J. Biol. Chem. 271:7916-7922.

7.   Meigs, T.E. and Simoni, R.D.  (1997) Farnesol as a regulator of HMG-CoA reductase degradation: characterization and role of farnesyl pyrophosphatase. Arch. Biochem Biophys. 345: 1-9.

8.   Glick, J.L., Meigs, T.E., Miron, A., and Casey, P.J. (1998) RGSZ1, a Gz-selective Regulator of G protein Signaling whose action is sensitive to the phosphorylation state of Gαz. J. Biol. Chem273: 26008-26013.

9.   Glick, J.L., Meigs, T.E., and Casey, P.J.  Identification of Regulators and Targets of G protein α subunits using the yeast two-hybrid system.  in G Proteins: Techniques of Analysis, D. R. Manning, ed.  CRC Press, 1999.

10. Glick, J.L., Meigs, T.E., and Casey, P.J.  G Proteins II: Focus on Gq, G12, and Gz. in Frontiers in Molecular Biology: GTPases, A. Hall, ed.  Oxford University Press, 2000.

11. Meigs, T.E., Fields, T.A., McKee, D.D., and Casey, P.J. (2001) Interaction of Gα12 and Gα13 with the cytoplasmic domain of cadherin provides a mechanism for ß-catenin release. Proc. Natl. Acad. Sci. USA 98: 519-524.

12. Kaplan, D.D,. Meigs, T.E., and Casey, P.J. (2001) Distinct regions of the cadherin cytoplasmic domain are essential for functional interaction with Gα12 and ß-catenin. J. Biol. Chem. 276: 44037-44043.

13. Meigs, T.E., Fedor-Chaiken, M., Kaplan, D.D., Brackenbury, R., and Casey, P.J. (2002) Gα12 and Gα13 negatively regulate the adhesive functions of cadherin. J. Biol. Chem. 277: 24594-24600.

14. Fedor-Chaiken, M., Meigs, T.E., Kaplan, D.D., and Brackenbury, R. (2003) Two regions of cadherin cytoplasmic domains are involved in suppressing motility of a mammary carcinoma cell line. J. Biol. Chem. 278: 52371-52378.

15. Kaplan, D.D., Meigs, T.E., Kelly, P., and Casey, P.J. (2004) Identification of a role for ß-catenin in the establishment of a bipolar mitotic spindle. J. Biol. Chem. 279: 10829-10832.

16. Zhu, D., Kosik, K.S., Meigs, T.E., Yanamadala, V., and Denker, B.M. (2004) Gα12 directly interacts with PP2A:  Evidence for Gα12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, Tau. J. Biol. Chem. 279: 54983-54986.

17. Meigs, T.E., Juneja, J., DeMarco, C.T., Stemmle, L.N., Kaplan, D.D., and Casey, P.J. (2005) Selective uncoupling of Gα12 from Rho-mediated signaling. J. Biol. Chem. 280: 18049-18055.

18. Andreeva, A.V., Kutuzov, M.A., Vaiskunaite, R., Profirovic, J., Meigs, T.E., Predescu, S., Malik, A.B., and Voyno-Yasenetskaya, T. (2005) Gα12 interaction with αSNAP induces VE-cadherin localization at endothelial junctions and regulates barrier function. J. Biol. Chem. 280: 30376-30383.

19. Zhu, D., Tate, R.I.*, Ruediger, R., Meigs, T.E., and Denker, B.M. (2007) Domains necessary for Gα12 binding and stimulation of protein phosphatase-2A (PP2A): is Gα12 a novel regulatory subunit of PP2A? Mol. Pharmacol. 71: 1268-1276.

20. Kelly, P., Casey, P.J., and Meigs, T.E. (2007) Biologic functions of the G12 subfamily of heterotrimeric G proteins: growth, migration, and metastasis. Biochemistry 46: 6677-6687.

21. Meigs, T.E. and Kaplan, D.D. (2008)  Isolation of centrosomes from cultured mammalian cells. Cold Spring Harbor Protocols; 2008; doi:10.1101/pdb.prot5039.

22. Yu, W., Ritchie, B.J.*, Su, X., Zhou, J., Meigs, T.E., and Denker, B.M. (2011) Identification of polycystin-1 and Gα12 binding regions necessary for regulation of apoptosis. Cell. Signal. 23: 213-221.

23. Ardawatia V.V., Masià-Balagué, M., Krakstad, B.F., Johansson, B.B., Kreitzburg, K.M.*, Spriet, E., Lewis, A.E., Meigs, T.E., and Aragay, A.M. (2011) Gα12 binds to the N-terminal regulatory domain of p120(ctn), and downregulates p120(ctn) tyrosine phosphorylation induced by Src family kinases via a RhoA-independent mechanism. Exp. Cell Res. 317: 293-306.

24. Meigs, T.E. and Lyakhovich, A. (2012) G protein alpha 12. in Encyclopedia of Signaling Molecules. S. Choi, editor, Springer Publishing.

25. Ritchie, B.J.*, Smolski, W.C.*, Montgomery, E.R.*, Fisher, E.S.*, Choi, T.Y.*, Olson, C.M.*, Foster, L.A.*, and Meigs, T.E. (2013) Determinants at the N- and C-termini of Gα12 required for activation of Rho-mediated signaling. J. Mol. Signal. 8: 3-16.

26. Montgomery, E.R.*, Temple, B.R.S., Peters, K.A., Tolbert, C.E., Booker, B.K.*, Martin, J.W.*, Hamilton, T.P.*, Tagliatela, A.C.*, Smolski, W.S.*, Rogers, S.L., Jones, A.M., and Meigs, T.E. (2014) Gα12 structural determinants of Hsp90 binding are necessary for Serum Response Element-mediated transcriptional activation. Mol. Pharmacol. 85: 586-597.

27. Martin, J.W.*, Cavagnini, K.S.*, Brawley, D.N.*, Berkley, C.Y.*, Smolski, W.C.*, Garcia, R.D.* Towne, A.L.*, Sims, J.R.*, and Meigs, T.E. (2016) A Gα12-specific binding domain in AKAP-Lbc and p114RhoGEF. J. Mol. Signaling 11(3): 1-17.

*indicates UNC Asheville undergraduate student who performed research in my laboratory; see publications 19, 22, 23, 25, 26, and 27.

Research Support

Ongoing Support

GlaxoSmithKline and C.D. Spangler Foundations (Endowed Professorship), 7.1.11 to 6.30.21
Provides an annual fund of $8000 for lab supplies and reagents, plus some additional funds for travel and summer undergraduate research stipends.  These funds support our project of performing evolutionary comparisons and chimera construction between different classes of G proteins to guide approaches for identifying determinants of Gα12 and Gα13 mediated signaling pathways.

Completed Support

UCRF Partnership Award: Meigs (PI), Stephen Rogers (Co-Investigator), 6.1.09 to 5.30.11
Lineberger Comprehensive Cancer Center
The objective of this study was to identify Gα12 cassette mutations disruptive to specific protein binding events, and examine the same mutations in Concertina for effects on S2 cell shape changes and motility, to identify novel effectors required for Gα12 stimulation of these cellular responses.
Total award: $100,500

Biotechnology Research Grant BRG1229: Meigs (PI), 9.1.07 to 6.30.09
North Carolina Biotechnology Center
“Dissection of an Intracellular Signaling Network through Engineering of Immobilized Effector Proteins: A Novel Approach for Identifying Gα12 Interactions Involved in Tumorigenesis”
In this study, we developed and refined an assay for immobilizing several Gα12 target proteins and examining their comparative ability to bind cassette substitution mutants of Gα12 in cell lysates.
Total award: $75,000

R01 CA100869: Patrick Casey (PI), Meigs (Co-Investigator), 2.1.04 to 1.31.09
National Cancer Institute
“G protein Involvement in Oncogenesis and Metastasis”
This study investigated the role of the trimeric G protein Gα12 in the origin and progression of cancer, through development and application of reagents designed to specifically disrupt the interaction of Gα12 with the cytoplasmic domain of cell-surface cadherins.

R21 CA91159: Patrick Casey (PI), Meigs (Co-Investigator), 3.1.01 to 2.28.03
National Cancer Institute
"Interaction of Gα12 with Cadherin Presents a Novel Target in Oncogenesis"
The objective of this project was to elucidate the functional consequences of activation-dependent interaction of Gα12 with cadherins.

National Research Service Award GM19119: 7.1.97 to 1.1.00
National Institute of Health
"Regulation of G protein-Mediated Signaling"
This was a postdoctoral fellowship, the objective of which was to clone and characterize a novel Regulator of G protein Signaling (RGS) protein, and to conduct yeast two-hybrid screens to identify molecular targets of heterotrimeric G proteins.