Marcus Smolka
Associate Professor

Marcus Smolka




Department of Molecular Biology & Genetics
339 Weill Hall
Cornell University
Ithaca, NY 14853-2703


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Marcus Smolka is an Associate Professor in the Department of Molecular Biology and Genetics, and a member of the Weill Institute for Cell and Molecular Biology (Weill Institute). He received a Ph. D. in Brazil, at the State University of Campinas, working with mass spectrometry and bacterial proteomics. During his graduation, Dr. Smolka was supported by a fellowship from the Sao Paulo state funding agency, FAPESP. He received further training in quantitative mass spectrometry with Dr. Ruedi Aebersold, at the Institute for Systems Biology (Seattle), working as an international visiting fellow. Dr. Smolka then moved to San Diego, CA, where he did his postdoctoral research at the Ludwig Institute for Cancer Research, working with DNA damage checkpoint kinases and phosphoproteomics in the laboratory of Dr. Huilin Zhou. He joined Cornell in 2008 and heads the Laboratory of Proteomics and Cell Signaling.

Research Description

Proteomics & DNA Damage Signaling

Our research is focused on the DNA damage checkpoint, an evolutionary conserved signaling pathway that functions to protect genomic integrity. We are particularly interested in understanding how dysfunctions in the DNA damage checkpoint kinases lead to genomic instability and, consequently, cancer. We are using mass spectrometry technologies, in combination with genetic and biochemical approaches, to study the organization, dynamics and regulation of DNA damage checkpoint signaling in normal and checkpoint-deficient cells. Currently, two interconnected projects are underway: (1) Development of state-of-the-art mass spectrometry-based technologies to characterize protein phosphorylation events in the cell; (2) Proteome-wide analysis of intra-S-phase checkpoint signaling and study of the checkpoint-dependent maintenance of replication fork stability.

Proteomic technology to study cell signalling

proteomic technology

Reversible protein phosphorylation is widely used by cells as a signaling mechanism. It regulates, directly or indirectly, most cellular processes. Protein kinases are the central coordinators of signaling, as they are the enzymes responsible for transferring a phosphate group from ATP to targeted protein substrates. Not surprising, perturbations in the action of kinases are associated with several human pathologies, including cancer. Understanding the molecular basis of kinase action and function is of critical importance for biomedical research. It requires knowledge of the kinase substrates, as well as comprehensive characterization of the dynamics and role of the phosphorylation events. Because many kinases are active in a cell and thousands of proteins are phosphorylated, the study of phosphorylation-mediated signaling pathways is challenging and powerful technologies are needed.

We have developed and applied quantitative mass spectrometry technologies for the phosphorylation analysis of protein complexes [1, 2], and for a global screen for in vivo kinase substrates [3, 4]. We are now expanding the use of these technologies to quantitatively characterize signaling dynamics at a proteome-wide scale.


DNA damage checkpoint signalingDNA damage checkpoint signaling

dna damage checkpoint

In the presence of genotoxic stress, DNA damage checkpoint kinases (see Fig. 2) play a central role in coordinating an elaborate cellular response that involves processes such as DNA repair, DNA replication, cell cycle control and gene transcription. Understanding how the checkpoint kinases contribute to the maintenance of genomic integrity has important implications for cancer research and may provide the basis of rational treatment. We have identified an extensive network of targets of the DNA damage checkpoint kinases in the model organism S. cerevisiae (budding yeast) [3]. A major challenge now is to understand the dynamic regulation of these targets.

We are using quantitative mass spectrometry to systematically characterize the intra-S-phase checkpoint signaling dynamics in yeast. Our goal is to understand how the checkpoint kinases maintain stability of the DNA replication fork, genomic integrity and cell viability.


  1. Smolka, M.B., et al., Dynamic Changes in Protein-Protein Interaction and Protein Phosphorylation Probed with Amine-reactive Isotope Tag. Mol Cell Proteomics, 2005. 4(9): p. 1358-69.
  2. Smolka, M.B., et al., An FHA domain-mediated protein interaction network of Rad53 reveals its role in polarized cell growth. J Cell Biol, 2006. 175(5): p. 743-53.
  3. Smolka, M.B., et al., Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. PNAS, 2007. 104(25): p. 10364-9.
  4. Albuquerque, C.P.*, Smolka, M. B.* et al., A multidimensional chromatography technology for in-depth phosphoproteome analysis. Mol Cell Proteomics, 2008. (*Joint first authors).


Ohouo, P., Oliveira, F. M., Almeida, B. S. and Smolka, M. B. DNA Damage Signaling Recruits the Rtt107-Slx4 Scaffolds via Dpb11 to Mediate Replication Stress Response. Mol. Cell 2010 Jul 30;39(2):300-6.

Smolka, M. B. Fine-tuning the DNA damage response: protein phosphatase 2A checks on CHK2. Cell Cycle. 2010 Mar;9(5):862-3. Epub 2010 Mar 1.

Wagner, M. V., Smolka, M. B., de Bruin, R. A., Zhou, H., Wittenberg, C., Dowdy, S. F. Whi5 Regulation by Site Specific CDK-Phosphorylation in Saccharomyces cerevisiae. PLoS ONE. 2009;4(1):e4300. Epub 2009 Jan 28.

Payne, S. H., Yau, M., Smolka, M. B., Tanner, S., Zhou, H. and Bafna, V. Phosphorylation-Specific MS/MS Scoring for Rapid and Accurate Phosphoproteome Analysis. J Proteome Res. 2008, 7(8):3373-3381.

Pham, P., Smolka M. B., Calabrese, P., Landolph, A., Zhang, K., Zhou, H. and Goodman, M. F. Impact of phosphorylation and phosphorylation-null mutants on the activity and deamination specificity of activation-induced cytidine deaminase. J Biol Chem. 2008

Albuquerque, C. P.*, Smolka, M. B.*, Eng, J. and Zhou, H. High-coverage phosphoproteome analysis using a HILIC based multi-dimensional chromatography. Mol Cell Proteomics. 2008.
*These authors contributed equally to this work.

Smolka, M. B., Albuquerque, C. P., Chen, S. and Zhou, H. Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. PNAS 2007, 104(25):10364-9.

Chen, S., Smolka, M. B. and H. Zhou. Mechanism of Dun1 activation by Rad53 phosphorylation in Saccharomyces cerevisiae. J Biol Chem. 2007, 282(2):986-95.

Martins, D., Astua-Monge, G., Coletta-Filho, H. D., Winck, F. V., Baldasso, P. A., Oliveira, B. M., Marangoni, S., Machado, M. A., Novello, J. C. and Smolka, M. B. Absence of Classical Heat Shock Response in the Citrus Pathogen Xylella fastidiosa. Curr Microbiol 2007, 54(2):119-23.

Smolka, M. B., Chen, S., Maddox, P. S., Enserink, J. M., Albuquerque, C. P., Wei, X. X., Schmidt, K. H., Desai, A., Kolodner, R. D. and Zhou, H. An FHA Domain-Mediated Protein Interaction Network of Rad53 Reveals its Role in Polarized Cell Growth. J Cell Biol. 2006, 175(5):743-53.

Enserink, J. M., Smolka, M. B., Zhou, H. and Kolodner, R. D. Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae. J Cell Biol. 2006, 175(5):729-41.

Pereira D. R., Martins D., Winck FV, Smolka M. B., Nishimura N. F., Rabelo-Goncalves E. M., Hara N. H., Marangoni S., Zeitune J. M. and Novello J. C. Comparative analysis of two-dimensional electrophoresis maps (2-DE) of Helicobacter pylori from Brazilian patients with chronic gastritis and duodenal ulcer: a preliminary report. Rev Inst Med Trop Sao Paulo. 2006, 48(3):175-7.

Smolka, M. B., Albuquerque, C. P., Chen, S. H., Schmidt, K. H., Wei, X. X., Kolodner, R. D. and Zhou, H. Dynamic Changes in Protein-Protein Interaction and Protein Phosphorylation Probed with Amine-reactive Isotope Tag. Mol Cell Proteomics 2005, 4(9):1358-69.

Macedo, M. L, Freire, M. G., Martins, L. T., Martinez, D. S., Gomes, V. M., Smolka, M. B., Toyama, M. H., Marangoni, S. and Coelho, L. C. Novel protein from Labramia bojeri A. DC. seeds homologue to Kunitz-type trypsin inhibitor with lectin-like properties. J Agric Food Chem. 2004, 52(25):7548-54.

Smolka, M. B., Martins, D., Winck, F. V., Santoro, C. E., Castellari, R. R., Ferrari, F., Brum, I. J., Galembeck, E., Coletta-Filho, H. D., Machado, M. A., Marangoni, S. and Novello, J. C.. Proteome Analysis of the Plant Pathogen Xylella fastidiosa Reveals Major Cellular and Extracellular Proteins and a Peculiar Codon Bias Distribution. Proteomics 2003, 3:224-37.

Smolka, M., Zhou, H. and Aebersold, R. Quantitative Protein Profiling Using Two-dimensional Gel Electrophoresis, Isotope-coded Affinity Tag Labeling, and Mass Spectrometry. Mol Cell Proteomics 2002, 1:19-29.

Smolka, M. B., Zhou, H., Purkayastha, S. and Aebersold, R. Optimization of the isotope-coded affinity tag-labeling procedure for quantitative proteome analysis. Anal Biochem 2001, 297:25-31.

Freire, M. G., Machado, O. L., Smolka, M. B., Marangoni, S., Novello, J. C. and Macedo, M. L. Isolation and characterization of isolectins from Talisia esculenta seeds. J Protein Chem 2001, 20:495-500.

Smolka, M. B., Zoppi, C. C, Alves, A. A., Silveira, L. R., Marangoni, S., Pereira-Da-Silva, L., Novello, J. C. and Macedo, D. V. HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats. Am J Physiol Regul Integr Comp Physiol. 2000, 279(5):R1539-45.

Smolka, M. B., Marangoni, S., Oliveira, B. and Novello, J. C. Purification and partial characterization of a thrombin-like enzyme, balterobin, from the venom of Bothrops alternatus. Toxicon 1998, 36(7):1059-63.