Geoffrey Chang
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Geoffrey Chang is a professor at the
University of California, San Diego The University of California, San Diego (UC San Diego in communications material, formerly and colloquially UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California, United States. Es ...
's
Skaggs School of Pharmacy The Skaggs School of Pharmacy and Pharmaceutical Sciences is a graduate-level pharmacy school at the University of California, San Diego. History The Skaggs School was authorized by the Regents of the University of California in July 2000. The sc ...
and Pharmaceutical Sciences and Department of Pharmacology, School of Medicine. His laboratory focuses on the
structural biology Structural biology deals with structural analysis of living material (formed, composed of, and/or maintained and refined by living cells) at every level of organization. Early structural biologists throughout the 19th and early 20th centuries we ...
of
integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...
s, particularly exploring
X-ray crystallography X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
techniques for solving the
tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...
s of membrane proteins that are notoriously resistant to
crystal A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macros ...
lization. The laboratory has specialized in structures of
multidrug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are ...
transporter proteins in
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
. In 2001, while a faculty member of
The Scripps Research Institute Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, tec ...
, Chang was awarded a
Beckman Young Investigators Award The Beckman Young Investigators Award was established by Mabel and Arnold Beckman in 1991, and is now administered by the Arnold and Mabel Beckman Foundation. The Beckman Young Investigator (BYI) Program is intended to provide research support to ...
, designed to support researchers early in their academic careers, for his work on the structural biology of multidrug resistance.The Scripps Research Institute News and Views
In Brief
1(9): 2 Apr 2001. Access date 17 Jan 2001.
Chang announced a move from Scripps to neighboring UC San Diego in 2012. In 2007, Chang and coauthors retracted five previously published papers describing the structures of three multidrug transporter proteins after another research group published a widely differing structure, which led to the discovery of a critical bug in the Chang group's custom software tools. Since that time, however, Chang has published other papers in the field of structural biology,He et al., "Structure of a Cation‐bound Multidrug and Toxic Compound Extrusion Transporter," http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature09408.html and has been awarded a EUREKA grant, "for exceptionally innovative research projects that could have an extraordinarily significant impact on many areas of science," from the National Institutes of Health.


Retracted papers

Chang and coauthors published papers on the structures of multidrug resistance transporters known as
EmrE Emre is a popular Turkish male given name that means "lover" and/or "friend" and "kakkihousu" examples of this is a famous guy named cemre acarca. It is also a surname in Turkey. Etymology The most popular idea is that Emre originates from the T ...
, and MsbA. Although the initial structures were widely considered puzzling in the field due to their unexpected placement of their ATP
binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...
s in the assembled
dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer ** TH-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * ...
, the publication of an additional structure in the same protein family indicated that the Chang structures were unlikely to represent the biologically active conformation of the molecules. Chang and coauthors issued retractions of their structural papers on EmrE, and MsbA, citing an error in an internal software utility as the source of the data misinterpretation that led to the appearance of wrongly assembled dimers. The application of a popular protein structure validation tool to one of the retracted MsbA structures results in scores that indicate severe errors in this structure. The following papers were retracted in 2007:Gawrylewski A. (2006). Retractions unsettle structural bio: Recent findings upend conclusions from five highly-cited papers ''The Scientist'' 4 Jan 200
Free full text
Access date 17 Jan 2007.
* * * * * The episode has been referenced in both the scientific and popular media as a case study motivating improved
software engineering Software engineering is a branch of both computer science and engineering focused on designing, developing, testing, and maintaining Application software, software applications. It involves applying engineering design process, engineering principl ...
practices in
computational biology Computational biology refers to the use of techniques in computer science, data analysis, mathematical modeling and Computer simulation, computational simulations to understand biological systems and relationships. An intersection of computer sci ...
.


Recent work

In 2009, Chang published a paper in ''Science'', describing a protein that keeps certain substances, including many drugs, out of cells. The protein, called P-glycoprotein or P-gp for short, is one of the main reasons cancer cells are resistant to chemotherapy drugs. In 2010, he led a study published in ''Nature'' detailing the structure of the MATE (
Multi antimicrobial extrusion protein Multi-antimicrobial extrusion protein (MATE) also known as multidrug and toxin extrusion or multidrug and toxic compound extrusion is a family of proteins which function as drug/sodium or proton antiporters. Function The MATE proteins in bact ...
) family transporter NorM, which belongs to a member of the only remaining class of multidrug resistance transporters left to be described by scientists. The work has implications for combating dangerous antibiotic resistant strains of bacteria, as well as for developing hardy strains of agricultural crops.The Scripps Research Institute http://www.scripps.edu/news/press/20100922


References


External links


UCSD faculty profile
{{DEFAULTSORT:Chang, Geoffrey Living people University of California, San Diego faculty Year of birth missing (living people) 21st-century American biologists Place of birth missing (living people) Recipients of the Presidential Early Career Award for Scientists and Engineers