Cotter, Robert J.

Department Affiliation: Primary: Pharmacology and Molecular Sciences; Secondary: Biophysics and Biophysical Sciences; Principal Professional Staff, Applied Physics Laboratory
Degree: Ph.D., Johns Hopkins University
Rank: Professor
Telephone Number: 410-955-3022
Fax Number: 410-955-3420
E-mail address: rcotter@jhmi.edu
School of Medicine Address: B-7 Biophysics Building, 725 N. Wolfe Street, Baltimore, MD 21205

Development of time-of-flight and ion trap mass spectrometry; applications of MALDI and electrospray mass spectrometry to immunology, protein structure analysis (including protein post-translational modifications) and epigenetics.

The laboratory has been a leader in the development of time-of-flight (TOF) mass spectrometry, including a tandem TOF with a curved-field reflectron for rapid peptide amino acid sequencing using high energy collisions.1,2 The laboratory has also developed ion trap mass spectrometers, a combined ion trap/time-of-flight mass spectrometer, a miniaturized TOF for rapid identification of microorganisms based upon their proteomes, and is currently designing a low power ion trap mass spectrometer for Mars below-surface exploration. In collaboration with the Heng Zhu laboratory we have constructed protein microarrays for direct analysis by MALDI mass spectrometry imaging.³

An effective procedure for N-terminal sulfonation4 enables de novo sequencing of proteins that is being used to elucidate ubiquitylation sites in proteins and ubiquitylating enzymes.5 As part of the Technical Center for Networks and Pathways (TCNP) of Lysine modifications, the laboratory has developed an approach for determining acetylation sites that has been used to investigate regulatory mechanisms in histone acetyl transferases (HATs)6,7 and a method for quantitating acetylation on specific histone sites using hyper-deuteroacetylation of unoccupied lysines that has been used to explore the role of sirtuins hst3 and Hst4p in yeast8 and to distinguish isoforms of hyperacetylated H3 and H4 tail regions in human HeLa cells. In a novel approach to biomarker discovery, supported by the NHLBI Center for Proteomics of Ischemia and Hypoxia, the laboratory is utilizing the albuminome, the proteins bound to albumin following albumin removal, to investigate potential clinically-useful indicators of heart disease.⁹

Representative Publications:

• Evans-Nguyen, K.M.; Tao,S.C.; Zhu,H.; Cotter, R.J., Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: detection of peptides in plasma Anal Chem 80 (2008) 1448-58. Pub Med Reference
  
• Karanam, B.; Wang, L.; Wang, D.; Liu, X.; Marmorstein, R.; Cotter, R.; Cole, P. A. Multiple roles for acetylation in the interaction of p300 HAT with ATF-2 Biochemistry 46 (2007) 8207-16. Pub Med Reference
  
• Celic I, Masumoto H, Griffith WP, Meluh P, Cotter RJ, Boeke JD, Verreault A., The sirtuins hst3 and Hst4p preserve genome integrity by controlling histone h3 lysine 56 deacetylation., Curr. Biol. 16 (2006)1280-9. Pub Med Reference
  
• Cotter, R.J.; Iltchenko, S.; Wang, D.; Gundry, R., Tandem Time-of-Flight (TOF/TOF) Mass Spectrometry and Proteomics, J. Mass Spectrom. Soc. Japan 53 (2005) 7-17. 

• Wang, D.; Cotter, R.J., Approach for Determining Protein Ubiquitination Sites by MALDI-TOF Mass Spectrometry, Anal. Chem. 77 (2005) 1458-66. Pub Med Reference
  
• Cotter, R.J.; Gardner, B.; Iltchenko, S.; English, R.D., Tandem Time-of-Flight Mass Spectrometry with a Curved Field Reflectron, Anal. Chem. 76 (2004) 1976-1981. Pub Med Reference
  
• Wang, D.; Kalb, S.R. and Cotter, R.J., Improved Procedures for N-Terminal Sulfonation of Peptides for Matrix-Assisted Laser Desorption/Ionization Post-Source Decay Peptide Sequencing, Rapid Commun. Mass Spectrom. 18 (2004) 96-102. Pub Med Reference
  
• Thompson, P.; Wang, D.; Wang, L.; Fulco, M.; Pediconi, N.; Zhang, D.; An W.; Ge Q.; Roeder, R.G.; Wong, J.; Levrero, M.; Sartorelli, V.; Cotter, R.J. and Cole, P.A., Regulation of the p300 HAT Domain via a Novel Activation Loop. Nature: Struct. Mol. Biol. 11 (2004) 308-15. Pub Med Reference
  
• Stanley, B.A.; Gundry, R.L.; Cotter, R.J.; Van Eyk, J.E., Heart Disease, Clinical Proteomics and Mass Spectrometry, Disease Markers 20 (2004) 167-178. Pub Med Reference
  

Other graduate programs in which Dr. Cotter participates:

BCMB Program
Anti-Cancer Drug Development Program
Chemistry-Biology Interface Program (CBI)

Development of time-of-flight and ion trap mass spectrometry; applications of MALDI and electrospray mass spectrometry to immunology, protein structure analysis (including protein post-translational modifications) and epigenetics.

The laboratory has been a leader in the development of time-of-flight (TOF) mass spectrometry, including a tandem TOF with a curved-field reflectron for rapid peptide amino acid sequencing using high energy collisions.1,2 The laboratory has also developed ion trap mass spectrometers, a combined ion trap/time-of-flight mass spectrometer, a miniaturized TOF for rapid identification of microorganisms based upon their proteomes, and is currently designing a low power ion trap mass spectrometer for Mars below-surface exploration. In collaboration with the Heng Zhu laboratory we have constructed protein microarrays for direct analysis by MALDI mass spectrometry imaging.³

An effective procedure for N-terminal sulfonation4 enables de novo sequencing of proteins that is being used to elucidate ubiquitylation sites in proteins and ubiquitylating enzymes.5 As part of the Technical Center for Networks and Pathways (TCNP) of Lysine modifications, the laboratory has developed an approach for determining acetylation sites that has been used to investigate regulatory mechanisms in histone acetyl transferases (HATs)6,7 and a method for quantitating acetylation on specific histone sites using hyper-deuteroacetylation of unoccupied lysines that has been used to explore the role of sirtuins hst3 and Hst4p in yeast8 and to distinguish isoforms of hyperacetylated H3 and H4 tail regions in human HeLa cells. In a novel approach to biomarker discovery, supported by the NHLBI Center for Proteomics of Ischemia and Hypoxia, the laboratory is utilizing the albuminome, the proteins bound to albumin following albumin removal, to investigate potential clinically-useful indicators of heart disease.⁹

Representative Publications:

• Evans-Nguyen, K.M.; Tao,S.C.; Zhu,H.; Cotter, R.J., Protein arrays on patterned porous gold substrates interrogated with mass spectrometry: detection of peptides in plasma Anal Chem 80 (2008) 1448-58. Pub Med Reference
  
• Karanam, B.; Wang, L.; Wang, D.; Liu, X.; Marmorstein, R.; Cotter, R.; Cole, P. A. Multiple roles for acetylation in the interaction of p300 HAT with ATF-2 Biochemistry 46 (2007) 8207-16. Pub Med Reference
  
• Celic I, Masumoto H, Griffith WP, Meluh P, Cotter RJ, Boeke JD, Verreault A., The sirtuins hst3 and Hst4p preserve genome integrity by controlling histone h3 lysine 56 deacetylation., Curr. Biol. 16 (2006)1280-9. Pub Med Reference
  
• Cotter, R.J.; Iltchenko, S.; Wang, D.; Gundry, R., Tandem Time-of-Flight (TOF/TOF) Mass Spectrometry and Proteomics, J. Mass Spectrom. Soc. Japan 53 (2005) 7-17. 

• Wang, D.; Cotter, R.J., Approach for Determining Protein Ubiquitination Sites by MALDI-TOF Mass Spectrometry, Anal. Chem. 77 (2005) 1458-66. Pub Med Reference
  
• Cotter, R.J.; Gardner, B.; Iltchenko, S.; English, R.D., Tandem Time-of-Flight Mass Spectrometry with a Curved Field Reflectron, Anal. Chem. 76 (2004) 1976-1981. Pub Med Reference
  
• Wang, D.; Kalb, S.R. and Cotter, R.J., Improved Procedures for N-Terminal Sulfonation of Peptides for Matrix-Assisted Laser Desorption/Ionization Post-Source Decay Peptide Sequencing, Rapid Commun. Mass Spectrom. 18 (2004) 96-102. Pub Med Reference
  
• Thompson, P.; Wang, D.; Wang, L.; Fulco, M.; Pediconi, N.; Zhang, D.; An W.; Ge Q.; Roeder, R.G.; Wong, J.; Levrero, M.; Sartorelli, V.; Cotter, R.J. and Cole, P.A., Regulation of the p300 HAT Domain via a Novel Activation Loop. Nature: Struct. Mol. Biol. 11 (2004) 308-15. Pub Med Reference
  
• Stanley, B.A.; Gundry, R.L.; Cotter, R.J.; Van Eyk, J.E., Heart Disease, Clinical Proteomics and Mass Spectrometry, Disease Markers 20 (2004) 167-178. Pub Med Reference
  

Other graduate programs in which Dr. Cotter participates:

BCMB Program
Anti-Cancer Drug Development Program
Chemistry-Biology Interface Program (CBI)