Download Sean W. Fanning, Ph.D.

University of Chicago
929 E. 57th St.
Chicago, IL 60637
Ben May Department for Cancer Research
815-901-2448
[email protected]
Sean W. Fanning, Ph.D.
Work Experience
Postdoctoral Fellow, University of Chicago, Mentor: Dr. Geoffrey L. Greene, Ph.D.
05/2012-Present
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Employed x-ray crystallography to determine the structure of the ERα ligand-binding domain (LBD) with the
SERM bazedoxifene, a recently approved drug to treat late-stage breast cancers. This was the first structure to
be solved of the protein-drug complex after 5 years of attempts by the University of Chicago and Pfizer.
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Solved x-ray crystal structures for the agonist and antagonist state of the ERα D538G mutant which is
important for acquired drug resistance in metastatic breast tumors. Collaborated with the Memorial SloanKettering Cancer Center, Scripps Florida and the University of Illinois to rationalize biochemical data to the
effects of somatic mutation observed in the breast cancer patient. Contributed to the first paper of this study
published in Nature Genetics titled “ESR1 ligand-binding domain mutations in hormone-resistant breast
cancer.”
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Developed numerous in vitro and in situ assays to reveal why somatic mutations of the ERα LBD lead to drug
resistance and increased metastasis in the breast cancer patient. Including an in vitro semi-high-throughput
differential scanning fluorimetry method to rapidly assess the relative binding affinities of lead compounds
against wild-type and mutant ERα LBD. This also included an in situ bioluminescent resonance energy
transfer system to explore the effect of somatic ERα mutation on coactivator recruitment within breast cancer
cell-lines (MCF-7, ZR75-1, MDAMB-231).
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Used SF9 and HEK 293-F expression systems along with FPLC to generate stable, highly pure, multi-domain
ERα and androgen receptor for structural biology and biophysical characterizations.
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Engaged surface plasmon resonance to characterize the binding affinity of the lead compounds for the ERα
LBD, DNA-binding affinity for multi-domain ERα and coactivator binding affinity. This revealed differential
affinities of currently approved SERMs for the clinically important somatic mutations to the ERα LBD.
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Presented at 5 cancer-related conferences and the 2014 AAAS meeting. These presentations covered work
related to high-throughput screening, breast cancer oncology, structural biology, biochemistry and biophysics.
Graduate Research Assistant, Northern Illinois University, Advisor: Dr. James R. Horn, Ph.D.
08/2008-05/2012
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Developed a high-throughput phage display method to engineer antibody conjugates for diagnostic and
affinity chromatographic applications. This entailed introducing novel functionality into an anti-protein
antibody binding interface while minimally impacting the original binding thermodynamics. Enzyme-linked
immunsorbant assays (ELISA), x-ray crystallography, isothermal titration calorimetry (ITC) and circular
dichroism were all used to characterize the engineered antibodies. Several papers have been published as a
result of these studies. I authored a paper published in Biochemistry named “A combinatorial approach to
engineering a dual-specific metal switch antibody.” I also authored a paper recently submitted to PEDS titled
“Structural basis for an engineered dual-specific antibody: conformational diversity leads to an
unconventional metal binding site.” And I co-authored a paper in Protein Science named “A combinatorial
histidine scanning library approach to engineer highly pH-dependent protein switches.” I was invited to speak
about these studies at the 2011 Gibbs Conference on Biothermodynamics.
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Used x-ray crystallography and ITC to characterize a novel antibody-drug binding interaction. This study
revealed a novel, non-canonical binding mechanism employed by a single-domain antibody to recognize the
drug methotrexate with a high affinity and specificity. As a result of this work, I authored of a paper that was
published in Protein Science titled “An anti-hapten camelid antibody reveals a cryptic binding site with
significant energetic contributions from a non-hypervariable loop.” This paper was the featured cover art for
the July 2011 issue of Protein Science.
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Collaborated with a laboratory in the Department of Biology at Northern Illinois University to investigate
virus protein-RNA interactions. Specifically, I used my protein expression and purification expertise to
generate pure viral coat proteins from the brome mosaic virus. As a result of this study, I co-authored a paper
published in Virus Research named “Mutations in the coat-protein-binding cis-acting RNA motifs debilitate
RNA recombination of Brome mosaic virus.”
Organized the seminar series for the Center for Biochemical and Biophysical studies at Northern Illinois
University. Hosted and introduced guest speakers.
Participated in the Chicago Structural Genomics for Infections Disease consortium with Dr. Timothy Hagen
where I contributed expertise in protein expression/purification, assay development and structural biology. I
mentored the beginning graduate students who were advised by Dr. Hagen and they have begun publishing
papers resulting from this work.
Intern, Perkins Products LLC
05/2007-08/2007, 05/2008-05/2008
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Developed proficiency in quality control methodologies and good laboratory practices by performing quality
control tests on metalworking fluids, lubricants, quenchants and cleaning fluids. This involved the use of
many analytical chemistry techniques such as GC/MS, infrared spectroscopy and x-ray fluorescence among
others.
Met with customers on-site to assess their needs then developed customized fluids to meet those needs. This
resulted in decreased cost and increased productivity for the customer.
Gained significant expertise in interfacing between scientists, engineers, salespeople and other business
personnel as a result of these internships.
Awards
Committee on Cancer Biology Postdoctoral Training Grant
11/2012
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Administered by the University of Chicago Biosciences Division, funded by the National Institutes of Health.
$150,000. For a grant titled “Determining the Role of Somatic Mutations in SERM-Resistant Breast Cancers
and the Generation of a New Class of SERMs to Treat Estrogen Receptor-dependent Breast Cancers.”
John D. Graham Scholarship
04/2010
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From Northern Illinois Department of Chemistry and Biochemistry for outstanding research by a graduate
student pursing a Ph.D. $1,500.
Student Research Grant
05/2009
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Center for Biochemical and Biophysical Studies, Northern Illinois University. $5,000.
Education
Northern Illinois University
2008-2012
Doctorate of Chemistry
Virginia Polytechnic Institute and State University (Virginia Tech)
2004-2008
Bachelors of Science in Biochemistry, Minor in Chemistry
DeKalb, IL
Blacksburg, VA