My research focuses on increasing the knowledge of gene function, integrating: biochemistry, technology development, proteomics and computational biology. Recently, I was the contact PI on a Grand Opportunity project supported by ARRA funding, with co-PI’s, Richard Roberts, Chief Scientific Officer of New England Biolabs, and Simon Kasif, Professor of Biomedical Engineering. This project has involved coordinated efforts of over 100 investigators at numerous institutions. COMBREX (Computational Bridges to Experiments) is an effort to bring computational and experimental biologists together, with the complementary goals of identifying and prioritizing important gene function predictions to test, and funding the necessary experiments through the issuance of small monetary grants. Since its inception, COMBREX has made contributions to: distinguishing experimentally validated gene function from those that are computationally predicted; serving as a public repository of novel gene function predictions; implementing a system of traceable evidence for predictions and gene annotation; prioritizing genes for functional validation; and actually funding the experiments. This project funded the experimental determination of 140 genes of unknown function. We have recently developed new methods for the experimental determination of gene function and applied it to six hypothetical proteins from Helicobacter pylori, using technology that has the potential to make a significant improvement on our knowledge of gene function. A final project in my lab is an analysis of peripheral leukocytes for the early diagnosis of prostate cancer. This project looks at cellular inflammatory markers in prostate cancer, benign prostatic hypertrophy and chronic prostatitis.

B. P. Anton, S. Kasif, R. J. Roberts, M. Steffen, “Objective: Biochemical Function.” Frontiers in Genetics 5 (2014). Link B. P. Anton, Y.-C. Chang, P. Brown, H.-P. Choi, L. L. Faller, J. Guleria, Z. Hu, N. Klitgord, A. Levy-Moonshine, A. Maksad, V. Mazumdar, M. McGettrick, L. Osmani, R. Pokrzywa, J. Rachlin, R. Swaminathan, B. Allen, G. Housman, C. Monahan, K. Rochussen, K. Tao, A. Bhagwat, S. Brenner, L. Columbus, V. d. Crécy-Lagard, D. Ferguson, A. Fomenkov, G. Gadda, R. D. Morgan, A. L. Osterman, D. A. Rodionov, I. A. Rodionova, K. E. Rudd, D. Söll, J. Spain, S.-y. Xu, A. Bateman, R. M. Blumenthal, J. M. Bollinger, W.-S. Chang, M. Ferrer, I. Friedberg, M. Galperin, J. Gobeill, D. Haft, J. Hunt, P. Karp, W. Klimke, C. Krebs, D. Macelis, R. Madupu, M. J. Martin, J. H. Miller, C. O’Donovan, B. Palssøn, P. Ruch, A. Setterdahl, G. Sutton, J. Tate, A. Yakunin, D. Tchigvintsev, R. Greiner, D. Horn, K. Sjölander, S. L. Salzberg, D. Vitkup, S. Letovsky, D. Segrè, C. DeLisi, R. J. Roberts, M. Steffen, S. Kasif, “The COMBREX Project: Design, Methodology, and Initial Results.” PLOS Biology 11(8):e1001638. (2013). Link H. P. Choi, S. Juarez, S. Ciordia, M. Fernandez, R. Bargiela, J. P. Albar, V. Mazumdar, B. P. Anton, S. Kasif, M. Ferrer, M. Steffen, “Biochemical Characterization of Hypothetical Proteins from.” PLoS One 8, e66605 (2013). PubMed M. Natarajan, G. M. Schiralli Lester, C. Lee, A. Missra, G. A. Wasserman, M. Steffen, D. S. Gilmour, A. J. Henderson, “NELF coordinates RNA polymerase II pausing, premature termination and chromatin remodeling to regulate HIV transcription.” J Biol Chem (2013). PubMed J. Flanigon, M. Kamali-Moghaddam, I. Burbulis, C. Annink, M. Steffen, P. Oeth, R. Brent, D. van den Boom, U. Landegren, C. Cantor, “Multiplex protein detection with DNA readout via mass spectrometry.” N Biotechnol 30, 153-8 (2013). PubMed D. E. Wood, H. Lin, A. Levy-Moonshine, R. Swaminathan, Y. C. Chang, B. P. Anton, L. Osmani, M. Steffen, S. Kasif, S. L. Salzberg, “Thousands of missed genes found in bacterial genomes and their analysis with COMBREX.” Biol Direct 7, 37 (2012). PubMed R. J. Roberts, Y. C. Chang, Z. Hu, J. N. Rachlin, B. P. Anton, R. M. Pokrzywa, H. P. Choi, L. L. Faller, J. Guleria, G. Housman, N. Klitgord, V. Mazumdar, M. G. McGettrick, L. Osmani, R. Swaminathan, K. R. Tao, S. Letovsky, D. Vitkup, D. Segre, S. L. Salzberg, C. Delisi, M. Steffen, S. Kasif, “COMBREX: a project to accelerate the functional annotation of prokaryotic genomes.” Nucleic Acids Res 39, D11-4 (2011). PubMed A. Bergerat, J. Decano, C. J. Wu, H. Choi, A. I. Nesvizhskii, A. M. Moran, N. Ruiz-Opazo, M. Steffen, V. L. Herrera, “Prestroke proteomic changes in cerebral microvessels in stroke-prone, transgenic[hCETP]-Hyperlipidemic, Dahl salt-sensitive hypertensive rats.” Mol Med 17, 588-98 (2011). PubMed G. G. Bushkin, D. M. Ratner, J. Cui, S. Banerjee, M. T. Duraisingh, C. V. Jennings, J. D. Dvorin, M. J. Gubbels, S. D. Robertson, M. Steffen, B. R. O’Keefe, P. W. Robbins, J. Samuelson, “Suggestive evidence for Darwinian Selection against asparagine-linked glycans of Plasmodium falciparum and Toxoplasma gondii.” Eukaryot Cell 9, 228-41 (2010). PubMed A. Carpentieri, D. M. Ratner, S. K. Ghosh, S. Banerjee, G. G. Bushkin, J. Cui, M. Lubrano, M. Steffen, C. E. Costello, B. O’Keefe, P. W. Robbins, J. Samuelson, “The antiretroviral lectin cyanovirin-N targets well-known and novel targets on the surface of Entamoeba histolytica trophozoites.” Eukaryot Cell 9, 1661-8 (2010). PubMed A. Chatterjee, S. Banerjee, M. Steffen, R. M. O’Connor, H. D. Ward, P. W. Robbins, J. Samuelson, “Evidence for mucin-like glycoproteins that tether sporozoites of Cryptosporidium parvum to the inner surface of the oocyst wall.” Eukaryot Cell 9, 84-96 (2010). PubMed S. Kasif, M. Steffen, “Biochemical networks: the evolution of gene annotation.” Nat Chem Biol 6, 4-5 (2010). PubMed V. L. Herrera, J. L. Decano, M. Steffen, N. Ruiz-Opazo, “Autophagy: insights from DEspR-deficiency and haploinsufficiency.” Autophagy 5, 259-62 (2009). PubMed K. Steiling, A. Y. Kadar, A. Bergerat, J. Flanigon, S. Sridhar, V. Shah, Q. R. Ahmad, J. S. Brody, M. E. Lenburg, M. Steffen, A. Spira, “Comparison of proteomic and transcriptomic profiles in the bronchial airway epithelium of current and never smokers.” PLoS ONE 4, e5043 (2009). PubMed C. J. Wu, T. Cai, K. Rikova, D. Merberg, S. Kasif, M. Steffen, “A predictive phosphorylation signature of lung cancer.” PLoS One 4, e7994 (2009). PubMed A. Saharia, L. Guittat, S. Crocker, A. Lim, M. Steffen, S. Kulkarni, S. A. Stewart, “Flap endonuclease 1 contributes to telomere stability.” Curr Biol 18, 496-500 (2008). PubMed X. Jiang, N. Nariai, M. Steffen, S. Kasif, E. D. Kolaczyk, “Integration of relational and hierarchical network information for protein function prediction.” BMC Bioinformatics 9, 350 (2008). PubMed V. L. Herrera, J. L. Decano, P. Bagamasbad, T. Kufahl, M. Steffen, N. Ruiz-Opazo, “Sex-specific hippocampus-dependent cognitive deficits and increased neuronal autophagy in DEspR haploinsufficiency in mice.” Physiol Genomics 35, 316-29 (2008). PubMed D. M. Ratner, J. Cui, M. Steffen, L. L. Moore, P. W. Robbins, J. Samuelson, “Changes in the N-glycome, glycoproteins with Asn-linked glycans, of Giardia lamblia with differentiation from trophozoites to cysts.” Eukaryot Cell 7, 1930-40 (2008). PubMed K. L. Van Dellen, A. Chatterjee, D. M. Ratner, P. E. Magnelli, J. F. Cipollo, M. Steffen, P. W. Robbins, J. Samuelson, “Unique posttranslational modifications of chitin-binding lectins of Entamoeba invadens cyst walls.” Eukaryot Cell 5, 836-48 (2006). PubMed R. Ahmad, D. H. Nguyen, M. A. Wingerd, G. M. Church, M. A. Steffen, “Molecular Weight Assessment of Proteins in Total Proteome Profiles Using 1D-PAGE and LC/MS/MS.” Proteome Sci 3, 6 (2005). PubMed