Kristen M. Varney
Biochemistry and Molecular Biology
Basement, NMR Suite
(410) 706-8335 (NMR room)
1997-1999: Research Assistant-Dept. of Chemistry, University of Colorado-Colorado Springs
- 1999-2004: Research Assistant-Dept. of Biochemistry, University of Maryland-Baltimore
- 2004-2007: Manager, UMB NMR Facility
- 2007-2010: Associate Director of the UMB NMR Facility
- 2007-present: Assistant Professor of Biochemistry & Molecular Biology
- 2011-present: Director of the UMB NMR Facility
- 2011-present: Co-Director of Structural Biology, Center for Biomolecular Therapeutics, University of Maryland, IBBR
Dr. Varney has worked as manager of the UMB NMR Shared Service Facility for over 7 years, promoting the use of Nuclear Magnetic Resonance Spectroscopy for use in ongoing and new NIH funded research projects at the University of Maryland School of Medicine. As Director of this facility Dr. Varney keeps the NMR spectrometers in good working condition (600 MHz, 800 MHz, and our recently purchased 950 MHz NMR), manages the NMR facility billing and ordering, and performs NMR-related research. Another major component of Dr. Varney's position as the Associate director of the UMB NMR Shared Service Facility is training users. This training includes assisting investigators in preparing an appropriate NMR sample, troubleshooting sample conditions, setting up and running all NMR experiments, processing and analysis of NMR data and use of all NMR-related computer software for NMR structure and dynamic characterization of proteins, protein complexes, and complexes involving biomolecular therapeutics and small molecule inhibitors. In addition, Dr. Varney works on several NMR and structure-based drug-design research projects including the characterization of S100 proteins (S100B, S100A4), S100-inhibitor complexes, and their regulation cancer progression and metastasis. This includes NMR structural studies of the metastasis-related protein Mts1 and its interaction with nonmuscle myosin IIA and the interactions between S100B with human mdm4 (hdm4) and p53. Specifically, Mts1 is known to be overexpressed in many metastatic cancers and interacts with a number of targets related to cell shape and motility. S100B is a tumor marker, and contributes to the down-regulation of p53 in several cancers including malignant melanoma. One goal for this work is to characterize the protein-protein interactions at the atomic level as necessary to inhibit specific S100-target protein interactions. Therefore, Dr. Varney also characterizes the structure/dynamics of inhibitor complexes of both S100A4 and S100B as well as for other rational drug design projects ongoing in laboratories of the Greenebaum Cancer Center and the Center for Biomolecular Therapeutics.
Lab Techniques and Equipment:
As director of the UMB SOM NMR core facility, Dr. Varney manages all aspects of data collection/processing/analysis for two Bruker NMR spectrometers (600 MHz Avance III and 800 MHz Avance). A third spectrometer (Bruker 950 MHz Avance III spectrometer) will be installed and available to users in the fall of 2011.
Ruminski, R., Underwood, S., Vallely, K., Smith, S., Synthesis and Characterization of [Ru(dpopâ?T)(2)]-(PF6)(2). A ruthenium(II) complex with the novel mixed-denticity bridging lligand dipyrido(2,3-alpha: 3â?T,2â?T-j)phenazine (dpopâ?T). (1998) Inorganic Chemistry, 37, 6528-6531.
Rustandi, R.R., Vallely, K.M., Varlamova, O., Klein, M.G., Almo, S.C., Bresnick, A.R., and Weber, D.J. 1H, 13C, 15N NMR sequence-specific assignments for human apo-Mts1 (S100A4) (2001) J. Biomol. NMR, 19, 381-382.
Vallely, K.M., Rustandi, R.R., Ellis, K.C., Varlamova, O., Bresnick, A.R., and Weber, D.J. Solution structure of human mts1 (S100A4) as determined by NMR spectroscopy (2002) Biochemistry, 41, 12670-12680.
Wilder, P.T., Baldisseri, D.M., Udan, R., Vallely, K.M., and Weber, D.J. Location of the Zn2+ binding site on S100B as determined by NMR spectroscopy and site-directed mutagenesis (2003) Biochemistry, 42, 13410-13421.
Wilder, P.T., Varney, K.M., Weiss, M.B., Gitti, R.K., Weber, D.J. Solution structure of zinc- and calcium-bound rat S100B as determined by nuclear magnetic resonance spectroscopy (2005) Biochemistry, 44, 5690-5702.
Markowitz, J., Rustandi, R.R., Varney, K.M., Wilder, P.T., Udan, R., Wu, S.L., Horrocks, W.D., Weber, D.J. Calcium-binding properties of wild-type and ef-hand mutants of S100B in the presence and absence of a peptide derived from the c-terminal negative regulatory domain of p53 (2005) Biochemistry, 44, 7305-7314.
Gitti, R.K., Wright, N.T., Margolis, J.W., Varney, K.M., Weber, D.J., Margolis, F.L. Backbone dynamics of the olfactory marker protein as studied by 15N NMR relaxation measurements (2005) Biochemistry, 44, 9673-9679.
Wright, N.T., Varney, K.M., Ellis, K.C., Markowitz, J., Gitti, R.K., Zimmer, D.B., Weber, D.J. The three-dimensional solution structure of Ca(2+)-bound S100A1 as determined by NMR spectroscopy (2005) J. Mol. Biol., 353, 410-426.
Garrett, S.C., Varney, K.M., Weber, D.J., Bresnick, A.R. S100A4, a mediator of metastasis (2006) J. Biol. Chem., 281, 677-680.
Wilder P.T., Lin J, Bair C.L., Charpentier T.H., Yang D., Liriano M., Varney K.M., Lee A., Oppenheim A.B., Adhya S., Carrier F., Weber D.J. Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B. (2006) Biochim Biophys Acta. 1763, 1284-1297.
Velarde J.J., Varney K.M., Inman K.G., Farfan M., Dudley E., Fletcher J., Weber D.J., Nataro J.P. Solution structure of the novel dispersin protein of enteroaggregative Escherichia coli. (2007) Mol Microbiol., 66, 1123-1135.
Rifat D, Wright N.T., Varney K.M., Weber D.J., Black L.W. Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure for a dedicated target. (2008) J. Mol. Biol., 375, 720-734.
Prosser B.L., Wright N.T., Hernandez-Ochoa E.O., Varney K.M., Liu Y., Olojo R.O., Zimmer D.B., Weber D.J., Schneider M.F. S100A1 binds to the calmodulin-binding site of ryanodine receptor and modulates skeletal muscle excitation-contraction coupling. (2008) J Biol Chem., 283, 5046-5057.
Malashkevich V.N., Varney K.M., Garrett S.C., Wilder P.T., Knight D., Charpentier T.H., Ramagopal U.A., Almo S.C., Weber D.J., Bresnick A.R. Structure of Ca2+-bound S100A4 and its interaction with peptides derived from nonmuscle myosin-IIA (2008) Biochemistry, 47, 5111-5126.
Charpentier T.H., Wilder P.T., Liriano M.A., Varney K.M., Pozharski E., MacKerell A.D. Jr, Coop A., Toth E.A., Weber D.J.. Divalent metal ion complexes of S100B in the absence and presence of pentamidine. (2008) J. Mol. Biol, 382, 56-73.
Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F., Weber D.J.. S100A1 and calmodulin compete for the same binding site on ryanodine receptor. (2008) J Biol Chem, 283, 26673-26683.
Wright NT, Inman KG, Levine JA, Cannon BR, Varney KM, Weber DJ. Refinement of the solution structure and dynamic properties of Ca(2+)-bound rat S100B. (2008) J Biomol NMR, 42, 79-286.
Bai G, Feng B, Wang JB, Varney KM, Shapiro M. Backbone assignment of HINT1 protein, a mouse histidine triad nucleotide binding protein. (2009) Biomol NMR Assign. 3, 57-59.
Wright N.T., Cannon B.R., Wilder P.T., Morgan M.T., Varney K.M., Zimmer D.B., Weber D.J. Solution Structure of S100A1 bound to the CapZ peptide (TRTK12). (2009) J Mol Biol, 386, 1265-1277.
Charpentier T.H., Wilder P.T., Liriano M.A., Varney K.M., Zhong S., Coop A., Pozharski E., MacKerell A.D. Jr, Toth E.A., Weber D.J. Small molecules bound to unique sites in the target protein binding cleft of calcium-bound S100B as characterized by nuclear magnetic resonance and X-ray crystallography. (2009) Biochemistry, 48, 6202-6212.
Charpentier TH, Thompson LE, Liriano MA, Varney KM, Wilder PT, Pozharski E, Toth EA, Weber DJ. The effects of CapZ peptide (TRTK-12) binding to S100B-Ca2+ as examined by NMR and X-ray crystallography. (2010) J Mol Biol, 396, 1227-1243.
Malashkevich VN, Dulyaninova NG, Ramagopal UA, Liriano MA, Varney KM, Knight D, Brenowitz M, Weber DJ, Almo SC, Bresnick AR. Phenothiazines inhibit S100A4 function by inducing protein oligomerization. (2010) Proc Natl Acad Sci, 107, 8605-8610
Wilder PT, Charpentier TH, Liriano MA, Gianni K, Varney KM, Pozharski E, Coop A, Toth EA, Mackerell AD, Weber DJ. In vitro screening and structural characterization of inhibitors of the S100B-p53 interaction. (2010) Int J High Throughput Screen., 1, 109-126
Manvilla BA, Varney KM, Drohat AC. Chemical shift assignments for human apurinic/apyrimidinic endonuclease 1. Biomol NMR Assign. 4, 5-8.
Yang Y, Berry AA, Lee WC, Garnett JA, Marchant J, Levine JA, Simpson PJ, Fogel SA, Varney KM, Matthews SJ, Nataro JP, Inman KG. Complete 1H, 13C and 15N NMR assignments for donor-strand complemented AafA, the major pilin of aggregative adherence fimbriae (AAF/II) from enteroaggregative E. coli. (2011) Biomol NMR Assign. 5, 1-5.