Jennifer Ekstrom

Research Interests

The Ekstrom lab uses X-ray crystallography to study the three-dimensional structures of biologically and medically important proteins. Currently, our focus is on proteins and protein complexes involved in transcriptional regulation, but we are also studying select enzymes with interesting functional properties and potential for drug design.

In collaboration with Arul Chinnaiyan (U Mich), we are structurally characterizing the multiprotein regulatory complexes formed from the polycomb-group (PcG) family of proteins. Polycomb-group complexes are involved in chromatin modification and in the stable repression of specific sets of genes; this repression plays a critical role in embryonic development and in maintaining the identity of differentiated cells during cell division.

The PcG protein EZH2 is upregulated in metastatic cancer, with higher concentrations of EZH2 correlating with worse prognoses, and lowered concentrations inhibiting cell proliferation in vitro.Increased EZH2 expression results in the repression of 163 different genes, including key transcription factors and cell-cycle regulators. Blocking EZH2 expression using RNA interference arrests cell growth. Therefore, EZH2 is an appealing target for novel “transcription-based” cancer therapies.MORE

Recent Publications

Svensson HG, Wedemeyer WJ, Ekstrom JL, Callender DR, Kortemme T, Kim DE, Sjobring U, Baker D. Contributions of amino acid side chains to the kinetics and thermodynamics of the bivalent binding of protein L to Ig kappa light chain. Biochemistry. 2004 Mar 9;43(9):2445-57.

Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL (2003). X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase. Structure. Sep;11(9):1071-8.

Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE, Ealick SE (2003). Mechanism of human S-adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant. Biochemistry. Mar 4;42(8):2386-95.

Bennett EM, Ekstrom JL, Pegg AE, Ealick SE (2002) Monomeric S-adenosylmethionine decarboxylase from plants provides an alternative to putrescine stimulation. Biochemistry. Dec 10;41(49):14509-17.

Ekstrom JL, Pauly TA, Carty MD, Soeller WC, Culp J, Danley DE, Hoover DJ, Treadway JL, Gibbs EM, Fletterick RJ, Day YS, Myszka DG, Rath VL. (2002). Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase. Chem Biol. Aug; 9(8):915-24. MORE