View My VisualCV Online: http://www.visualcv.com/ketchemr

Objective

To utilize my skills and experience in computational structural biology, protein and antibody engineering and optimization, and team based therapeutic development to aid in the discovery of cures for and treatment of illness and disease.

Interests

In my current position I lead the cross-site and multidisciplinary Protein and Antibody Optimization group, responsible for engineering all biologics that come through Amgen's pipeline. My research direction is focused on computational structural biology while also applying my skills to broader platform review and direction. Working in areas of antibody design, epitope mapping, molecular assessment, stability engineering, construct design, protein engineering and serving on therapeutic area teams to lead target development.

  • Computation structural biology
  • Antibody design
  • Protein stability engineering
  • Therapeutic development
  • Protein structure analysis
  • Expert user of the Molecular Operating Environment
  • Project team environments
  • Computational and experimental approaches to understanding and controlling biophysical properties of biological macromolecules

Publications

Peer Reviewed:

 

  1. Native-state solubility and transfer free energy as predictive tools for selecting excipients to include in protein formulation development studies
    Douglas D. Banks, Ramil F. Latypov, Randal R. Ketchem, Jon Woodard, Joanna L. Scavezze, Christine C. Siska, Vladimir I. Razinkov
    Journal of Pharmaceutical Sciences, v101, n8, p2720, 2012

     

  2. Chemical Modifications in Therapeutic Protein Aggregates Generated under Different Stress Conditions
    Quanzhou Luo, Marisa K. Joubert, Riki Stevenson, Randal R. Ketchem, Linda O. Narhi, and Jette Wypych
    The Journal of Biological Chemistry, v286, 25134-25144, 2011

     

  3. In Vivo Crystallization of Human IgG in the Endoplasmic Reticulum of Engineered Chinese Hamster Ovary (CHO) Cells
    Haruki Hasegawa, John Wendling, Feng He, Egor Trilisky, Riki Stevenson, Heather Franey, Francis Kinderman, Gary Li, Deirdre Murphy Piedmonte, Timothy Osslund, Min Shen, Randal R. Ketchem
    The Journal of Biological Chemistry, v286, 19917-19931, 2011

     

  4. Diverse functions of reactive cysteines facilitate unique biosynthetic processes of aggregate-prone interleukin-31
    Min Shen, Sophia Siu, Samantha Byrd, Kurt H. Edelmann, Neha Patel, Randal R. Ketchem, Christopher Mehlin, Heather A. Arnett, Haruki Hasegawa
    Experimental Cell Research, v317, 976-993, 2011

     

  5. Histidine Residue Mediates Radical-induced Hinge Cleavage of Human IgG1
    Zac Yates, Guna Kannan, Hongxing Zhou, Zhonghua Hu, Zhi Liu, Randal R. Ketchem, and Boxu Yan
    J. Biol. Chem., v285, n24, 18662-18671, 2010

     

  6. Glutamine-linked and Non-consensus Asparagine-linked Oligosaccharides Present in Human Recombinant Antibodies Define Novel Protein Glycosylation Motifs
    John F. Valliere-Douglass, Catherine M. Eakin, Alison Wallace, Randal R. Ketchem, Wesley Wang, Michael J. Treuheit, and Alain Balland
    J. Biol. Chem., v285, n21, 16012-16022, 2010

     

  7. A Diversity of Antibody Epitopes can Induce Signaling through the Erythropoietin Receptor
    Ai Ching Lim, Randal R Ketchem, Luis Borges, Teresa Carabeo, Jane Carter, Joseph E. Hoover, Zhonghua Hu, Michael Wittekind, Hongxing Zhou and Christopher Mehlin
    Biochemistry, v49, 3797-3804, 2010

     

  8. A Central Nervous System-Restricted Isoform of the Interleukin-1 Receptor Accessory Protein Modulates Neuronal Responses to Interleukin-1
    Dirk E. Smith, Brian P. Lipsky, Chris Russell, Randal R. Ketchem, Jacqueline Kirchner, Kelly Hensley, Yangyang Huang, Wilma J. Friedman, Vincent Boissonneault, Marie-Michèle Plante, Serge Rivest and John E. Sims
    Immunity, v30, n6, 817-831, 2009

     

  9. Electrophoretic evidence for the presence of structural isoforms specific for the IgG2 isotype
    Amy Guo, Mei Han, Theresa Martinez, Randal R. Ketchem, Shawn Novick, Claudia Jochheim, Alain Balland
    Electrophoresis, 29, 2550-2556, 2008

     

  10. A role for the MHC class I-like Mill molecules in nutrient metabolism and wound healing
    Brian A. Rabinovich, Randal R. Ketchem, Martin Wolfson, Lynn Goldstein, Marylin Skelly and David Cosman
    Immunology and Cell Biology, v86, 489-496, 2008

     

  11. Disulfide Connectivity of Human Immunoglobulin G2 Structural Isoforms
    Theresa Martinez, Amy Guo, Martin J. Allen, Mei Han, Danielle Pace, Jay Jones, Ron Gillespie, Randal R. Ketchem, Yuling Zhang, and Alain Balland
    Biochemistry, v47, 7496-7508, 2008

     

  12. Biophysical Characterization of Structural Properties and Folding of Interleukin-1 Receptor Antagonist
    Ramil F. Latypov, Timothy S. Harvey, Dingjiang Liu, Pavel V. Bondarenko, Tadahiko Kohno, Roger A. Fachini II, Robert D. Rosenfeld, Randal R. Ketchem, David N. Brems, and Andrei A. Raibekas
    Journal of Molecular Biology, v368, 1187-1201, 2007

     

  13. A Single Amino Acid Difference between Human and Monkey Interleukin (IL)-1B Dictates Effective Binding to Soluble Type II IL-1 Receptor
    Dirk E. Smith, Randal R. Ketchem, Heather Moore, Zachary Anderson, Blair R. Renshaw, Della J. Friend, and John E. Sims
    The Journal of Biological Chemistry, v277, n49, 47619-47625, 2002

     

  14. Biophysical Characterization of a Soluble CD40 Ligand (CD154) Coiled-Coil Trimer: Evidence of a Reversible Acid-Denatured Molten Globule
    James E. Matsuura, Arvia E. Morris, Randal R. Ketchem, Emory H. Braswell, Ralph Klinke, Wayne R. Gombotz, and Richard L. Remmele, Jr.
    Archives of Biochemistry and Biophysics, v392, n2, 208-218, 2001

     

  15. Four New Members Expand the Interleukin-1 Superfamily
    Dirk E. Smith, Blair R. Renshaw, Randal R. Ketchem, Marek Kubin, Kirsten E. Garka, and John E. Sims
    The Journal of Biological Chemistry, v275, n2, 1169-1175, 2000

     

  16. Binding-Induced Activation of DNA Alkylation by Duocarmycin SA: Insights from the Structure of an Indole Derivative-DNA Adduct
    Jason R. Schnell, Randal R. Ketchem, Dale L. Boger, and Walter J. Chazin
    Journal of the American Chemical Society, v121, 5645-5652, 1999

     

  17. The three-dimensional structure of Ca2+-bound calcyclin: implications for Ca2+-signal transduction by S100 proteins
    Mallika Sastry, Randal R Ketchem, Orlando Crescenzi, Christoph Weber, Michael J Lubienski, Hiroyoshi Hidaka and Walter J Chazin
    Structure, v6, 223-231, 1998

     

  18. High-resolution polypeptide structure in a lamellar phase lipid environment from solid state NMR derived orientational constraints
    RR Ketchem, B Roux and TA Cross
    Structure, v5, 1655-1669, 1997

     

  19. Macromolecular structural elucidation with solid-state NMR-derived orientational constraints
    R. R. Ketchem, K. -C. Lee, S. Huo, and T. A. Cross
    Journal of Biomolecular NMR, v8,1-14, 1996

     

  20. Conformational trapping in a membrane environment: A regulatory mechanism for protein activity?
    S. Arumugam, S. Pascal, C. L. North, W. Hu, K-C. Lee, M. Cotten, R. R. Ketchem, F. Xu, M. Brenneman, F. Kovacs, F. Tian, A. Wang, S. Huo, and T. A. Cross
    Proceedings of the National Academy of Sciences of the United States of America, v93, 5872-5876, 1996

     

  21. High-Resolution Conformation of Gramicidin A in a Lipid Bilayer by Solid-State NMR
    R. R. Ketchem, W. Hu, T. A. Cross
    Science, v261, 1457-1460, 1993

     

Invited:

 

  1. Computational Refinement Through Solid State NMR and Energy Constraints of a Membrane Bound Polypeptide.
    R.R. Ketchem, B. Roux and T.A. Cross
    Biological Membranes: A Molecular Perspective from Computation and Experiment, K.M. Merz and B. Roux, Birkhauser Boston, 1996

     

  2. Structure and dynamics from solid state NMR spectroscopy
    RR Ketchem, W Hu, F Tian and TA Cross
    Structure, v2, 699-701, 1994

     

  3. High Resolution Polypeptide Structure in Anisotropic Environments: The Gramicidin Channel
    T.A. Cross, R.R. Ketchem, W. Hu, K.C. Lee, N.D. Lazo and S. Huo
    Proceedings of the Conference on Stable Isotope Applications in Biomolecular Structure and Mechanisms, 1994

     

  4. Structure and Dynamics of a Membrane Bound Polypeptide
    T.A. Cross, R.R. Ketchem, W. Hu, K.C. Lee, N.D. Lazo and C.L. North
    Bulletin of Magnetic Resonance v14, 96-101, 1993

     

Patents Issued:

 

  1. IL-1F6 Polypeptides
    Filed: September 10, 2007
    Issued: October 11, 2011
    Sims, John E.; Renshaw, Blair R.; Gabel, Christopher; Towne, Jennifer E.; Ketchem, Randal R.
    United States Patent 8,034,771
    PDF of issued patent.

     

  2. TWEAK receptor
    Filed: January 16, 2009
    Issued: November 9, 2010
    Kim, Kristine M.; Wiley, Steven R.; Ketchem, Randal R.; Fanslow, III, William C.
    United States Patent 7,829,675
    PDF of issued patent.

     

  3. TRAIL Receptor-2 Polypeptides and antibodies
    Published: August 2, 2007
    Issued: April 21, 2009
    Gliniak, Brian; Yang, Xiao-Dong; Wong-Madden, Sharon; Foltz, Ian; Feng, Xiao; Fitch, Alison; Foster, Stephen; Ketchem, Randal R.
    United States Patent 7,521,048
    PDF of issued patent.

     

  4. TWEAK receptor
    Published: September 22, 2005
    Issued: February 24, 2009
    Kim, Kristine M.; Wiley, Steven R.; Ketchem, Randal R.; Fanslow, William C. III
    United States Patent 7,495,086
    PDF of issued patent.

     

Patents Published:

 

  1. HUMAN IL-23 ANTIGEN BINDING PROTEINS
    United States Patent Application: 20130004501
    Filing Date: October 26, 2010
    Publication Date: January 3, 2013
    Inventors: Towne, Jennifer E.; Cheng, Janet D.; O'Neill, Jason C.; Zhang, Yu; Sun, Yu; Cerne, Heather; Piper, Derek E.; Ketchem, Randal R.
    PDF of patent application.

     

  2. ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)
    United States Patent Application: 20120213797
    Filing Date: May 3, 2012
    Publication Date: August 23, 2012
    Inventors: Jackson, Simon Mark; Walker, Nigel Pelham Clinton; Piper, Derek Evan; Shan, Bei; Shen, Wenyan; Chan, Joyce Chi Yee; King, Chadwick Terence; Ketchem, Randal Robert; Mehlin, Christopher; Carabeo, Teresa Arazas; Cao, Qiong
    PDF of patent application.

     

  3. ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)
    United States Patent Application: 20120093818
    Filing Date: June 30, 2011
    Publication Date: April 19, 2012
    Inventors: Jackson, Simon Mark; Walker, Nigel Pelham Clinton; Piper, Derek Evan; Shan, Bei; Shen, Wenyan; Chan, Joyce Chi Yee; King, Chadwick Terence; Ketchem, Randal Robert; Mehlin, Christopher; Carabeo, Teresa Arazas; Cao, Qiong
    PDF of patent application.

     

  4. ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)
    United States Patent Application: 20120020976
    Filing Date: October 3, 2011
    Publication Date: January 26, 2012
    Inventors: Jackson, Simon Mark; Walker, Nigel Pelham Clinton; Piper, Derek Evan; Shan, Bei; Shen, Wenyan; Chan, Joyce Chi Yee; King, Chadwick Terence; Ketchem, Randal Robert; Mehlin, Christopher; Carabeo, Teresa Arazas; Cao, Qiong
    PDF of patent application.

     

  5. ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)
    United States Patent Application: 20120020975
    Filing Date: October 3, 2011
    Publication Date: January 26, 2012
    Inventors: Jackson, Simon Mark; Walker, Nigel Pelham Clinton; Piper, Derek Evan; Shan, Bei; Shen, Wenyan; Chan, Joyce Chi Yee; King, Chadwick Terence; Ketchem, Randal Robert; Mehlin, Christopher; Carabeo, Teresa Arazas; Cao, Qiong
    PDF of patent application.

     

  6. IL-1 FAMILY VARIANTS
    United States Patent Application: 20120020918
    Filing Date: September 10, 2007
    Publication Date: January 26, 2012
    Inventors: Sims, John E.; Renshaw, Blair R.; Gabel, Christopher; Towne, Jennifer E.; Ketchem, Randal R.
    PDF of patent application.

     

  7. ANTI-HEPCIDIN ANTIBODIES AND METHODS OF USE
    United States Patent Application: 20110150888
    Filing Date: April 28, 2009
    Publication Date: June 23, 2011
    Inventors: Foltz, Ian; Gallo, Michael; Cooke, Keegan; Ketchem, Randal R.; Mehlin, Christopher
    PDF of patent application.

     

  8. ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)
    United States Patent Application: 20110027287
    Filing Date: October 12, 2010
    Publication Date: February 3, 2011
    Inventors: Jackson, Simon Mark; Walker, Nigel Pelham Clinton; Piper, Derek Evan; Shan, Bei; Shen, Wenyan; Chan, Joyce Chi Yee; King, Chadwick Terence; Ketchem, Randal Robert; Mehlin, Christopher; Carabeo, Teresa Arazas; Cao, Qiong
    PDF of patent application.

     

  9. TWEAK Receptor
    United States Patent Application: 20110020267
    Filing Date: October 6, 2010
    Publication Date: January 27, 2011
    Inventors: Kim, Kristine M.; Wiley, Steven R.; Ketchem, Randal R.; Fanslow III, William C.
    PDF of patent application.

     

  10. Polypeptides and Antibodies
    United States Patent Application: 20090226438
    Filed: April 2, 2009
    Inventors: Gliniak, Brian; Yang, Xiao-Dong; Wong-Madden, Sharon; Foltz, Ian; Feng, Xiao; Fitch, Alison; Foster, Stephen; Ketchem, Randal R.

     

  11. TWEAK RECEPTOR
    United States Patent Application: 20090137036
    Filed: January 16, 2009
    Inventors: KIM, KRISTINE M.; Wiley, Steven R.; Ketchem, Randal R.; Fanslow, III, William C.

     

  12. ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)
    United States Patent Application: 20090142352
    Filed: August 22, 2008
    Inventors: Jackson, Simon Mark; Walker, Nigel Pelham Clinton; Piper, Derek Evan; Shan, Bei; Shen, Wenyan; Chan, Joyce Chi Yee; King, Chadwick Terence; Ketchem, Randal Robert; Mehlin, Christopher; Carabeo, Teresa Arazas; Cao, Qiong

     

  13. IL-1 family variants
    United States Patent Application: 20080241096
    Filed: September 10, 2007
    Inventors: Sims, John E.; Renshaw, Blair R.; Gabel, Christopher; Towne, Jennifer E.; Ketchem, Randal R.

     

  14. Erythropoietin receptor agonists
    United States Patent Application: 20080124340
    Filed: April 13, 2007
    Inventors: Borges, Luis G.; Ketchem, Randal R.; Lim, Ai Ching; Mehlin, Christopher; Zhou, Hongxing

     

  15. Human cytokine and alpha-helix-containing polypeptides
    United States Patent Application: 20070072249
    Filed: December 6, 2006
    Inventors: Baum, Peter R.; Ketchem, Randal R.; DuBose, Robert F.; Wiley, Steven R.; Kerkof, Keith N.

     

  16. Cytokine polypeptides
    United States Patent Application: 20070081973
    Filed: November 20, 2006
    Inventors: Baum, Peter R.; Mosley, Bruce A.; Ketchem, Randal R.; Taylor, Scott L.

     

  17. Polypeptides and antibodies
    United States Patent Application: 20070179086
    Filed: August 28, 2006
    Inventors: Gliniak, Brian; Yang, Xiao-Dong; Wong-Madden, Sharon; Foltz, Ian; Feng, Xiao; Fitch, Alison; Foster, Stephen; Ketchem, Randal R.

     

  18. Human and murine cytokine polypeptides
    United States Patent Application: 20060110772
    Filed: July 7, 2005
    Inventors: Baum, Peter R.; Mosley, Bruce A.; Ketchem, Randal R.

     

  19. TWEAK receptor
    United States Patent Application: 20050208046
    Filed: October 22, 2004
    Inventors: Kim, Kristine M.; Wiley, Steven R.; Ketchem, Randal R.; Fanslow, William C. III

     

  20. Human and murine cytokine polypeptides
    United States Patent Application: 20030134306
    Filed: October 2, 2002
    Inventors: Baum, Peter R.; Mosley, Bruce A.; Ketchem, Randal R.

     

  21. Cytokine polypeptides
    United States Patent Application: 20030104579
    Filed: May 8, 2002
    Inventors: Baum, Peter R.; Mosley, Bruce A.; Ketchem, Randal R.; Taylor, Scott L.

     

Invited Talks:

 

  1. Antibody Optimization Before the Storm
    PepTalk 2013
    January 23, 2013

     

  2. Mitigation of Monoclonal Antibody Viscosity by Modification of Protein Surface Charge
    Protein Engineering Summit (PEGS) 2012
    April 30, 2012

     

  3. Mediating Antibody Viscosity
    Chemical Computing group User Group Meeting
    June 3, 2010

     

  4. Mining the Human Genome Using Protein Structure Homology
    Pacific Lutheran University
    September 11, 2002

     

  5. Mining the Human Genome Using Protein Structure Homology
    Western Washington University
    June 5, 2002

     

Ph.D. Dissertation:

Structural Determination and Refinement of the Gramicidin A Transmembrane Channel as Studied by Solid State Nuclear Magnetic Resonance Spectroscopy
Randal R. Ketchem
FSU call number QP551.K47 1995.
PDF Version.


Photography:

 

  1. Sperry Peak, Fresh Snow
    Randal R. Ketchem
    Outdoor Photographer, Favorite Places, November, 2011

     

  2. Sunrise on Sea Stacks, Reflected, Oceanside, Oregon
    Randal R. Ketchem
    Outdoor Photographer, 2009 Calendar

     

  3. Coal Lake, Washington
    Randal R. Ketchem
    Outdoor Photographer, Favorite Places, March, 2006

Education

Florida State University

Tallahassee, FL, United States
Aug 1989 - Dec 1995
Ph.D., Molecular Biophysics

Ph.D. in Molecular Biophysics at the Florida State University and National High Magnetic Field Laboratory working on Solid State Nuclear Magnetic Resonance Spectroscopy and computational methods for the structure determination of the Gramicidin A transmembrane channel. Advisor Timothy A. Cross.

University of West Florida

Pensacola, FL, United States
Aug 1987 - Aug 1989
B.S., Chemistry

While obtaining my B.S. in Chemistry I worked in the research lab of Dr. John Riehm, performing protein purification using gel columns and HPLC, and performing solid phase peptide synthesis.

Employment History

Amgen Inc

Seattle, WA, United States
Jan 2011 - Present
Scientific Director 

I lead the Protein and Antibody Optimization team, responsible for engineering all biologics that come through Amgen's pipeline. My research direction is focused on computational structural biology while also applying my skills to broader platform review and direction. Working in areas of antibody design, epitope mapping, molecular assessment, stability engineering, construct design, protein engineering and serving on therapeutic area teams to lead target development.

Amgen Inc.

Seattle, WA, United States
Jul 2002 - Jan 2011
Principal Scientist 

My move to Amgen was due to Immunex being purchased by Amgen. My research direction is focused on computational structural biology while also applying my skills to broader platform review and direction. Working in areas of antibody epitope mapping, molecular assessment, stability engineering, construct design, protein engineering and serving on therapeutic area teams to lead target development.

Immunex Corporation

Seattle, WA, United States
Nov 1997 - Jul 2002
Scientist 

Computational structural biology involving protein structure determination, analysis and design, protein target discovery, and protein engineering.

The Scripps Research Institute

La Jolla, CA, United States
Feb 1996 - Nov 1997
Postdoctoral Fellow 

Postdoctoral research in Molecular Biology at The Scripps Research Institute working on High Resolution Nuclear Magnetic Resonance Spectroscopy and computational methods for the structure determination of calcium loaded calcyclin and small molecule binders to the minor groove of DNA.

Florida State University

Tallahassee, FL, United States
Dec 1995 - Feb 1996
Postdoctoral Fellow 

Continued as a Postdoctoral Fellow under my Ph.D. advisor, Timothy A. Cross.