Elizabeth Goldsmith, Ph.D.

Professor

Endowed Title: Patti Bell Brown Professorship in Biochemistry

Department: Biophysics, Biochemistry

Graduate Programs: Molecular Biophysics

Biography

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I am a structural biologist interested in how proteins are regulated by conformational changes, and have made significant contributions over the years to the analysis of protein kinases. Protein kinases represent a diverse set of molecular machines, carrying out precise programs of binding events, conformational changes and chemistry, often in a cascade.  Our work has primarily focused on MAP kinase modules, and recently we have begun to study another short cascade comprised of the kinases WNK and OSR1/SPAK.  These enzymes are medically important. Further, WNK1 itself is a salt sensor, a process that there is almost no data on.  We are currently studying how WNK is regulated by salt or chloride, and how salt effects are transmitted into the next conformational step, which is breaking interactions with an autoinhibitory domain in WNK1.  Our goal is a complete picture of the mechanism of the cascade.  A secondary goal of my work is to learn enough about the mechanism of action of protein kinases to identify novel approaches toward drug discovery.

Over the past few years, my laboratory has significantly expanded the repertoire of biophysical methods we are using.  We are using rt-PCR machine to do differential scanning fluorimetry (DSF) to find inhibitors of one of the kinases we are studying, TAO2.  We have in press a paper on using TROSY NMR spectroscopy to observe conformational changes in the p38 MAP kinase, work done collaboratively with Kevin Gardner.  We also have a Thermofinnigan mass spectrometer being used to determine phosphorylation order in MAP kinase modules. 

In early work in this lab we also studied the serpin family of protease inhibitors, which undergo very interesting irreversible energy driven conformational changes (folding initially into a configuration that is not the most stable available to the polypeptide).

Education

Undergraduate University of California-Los Angeles (1967)
Graduate School University of California-Los Angeles (1971)

Research Interests

  • Conformation regulation of protein molecules
  • Protein kinases, how regulated, how inhibited

Publications

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Honors/Awards

  • Patti L. Brown (Chilton) Professor of Biochemistry
    Endowed Professorship (2011)
  • NIH
    Postdoctoral Fellowship (1973)
  • UCLA
    Graduate Woman of the Year (1971)
  • UCLA
    Honors in Chemistry (1967)

Professional Associations/Affiliations

  • American Crystallographic Association
  • Biophysical Society
  • Protein Society