![Michael D. Brenowitz](https://assets.montefioreeinstein.org/profiles/images/Brenowitz_Michael_PhD_2x_2.jpg)
Michael D. Brenowitz, Ph.D.
- Professor, Department of Biochemistry
- Professor, Department of Molecular Pharmacology
Area of research
- Exploring how protein, DNA, and RNA structure, folding, and assembly determines the biological function of these macromolecules.
Phone
Location
- Albert Einstein College of Medicine Jack and Pearl Resnick Campus 1300 Morris Park Avenue Forchheimer Building 311 Bronx, NY 10461
Research Profiles
Professional Interests
Biology is a dynamic process. Among the myriad array of reversible association reactions that constitute life, small molecules bind to proteins, proteins self-associate and bind to other proteins and nucleic acids and nucleic acids fold and bind to each other in elaborate processing, signaling and regulatory cascades. What is common to these processes is the physical chemistry that underlies these interactions. For example, electrostatic interactions mediate both the binding of proteins to DNA and the folding of RNA. Proteins that mimic the electrostatic character of DNA may competitively regulate DNA binding by other proteins. Our laboratory seeks answers to questions related to the structure – function relationships that govern macromolecular function by combining quantitative analysis with innovative approaches.
- The longest running programmatic theme of our laboratory is the study of the mechanisms by which proteins recognize and bind specific sequences of DNA. We have turned our attention to proteins involved in epigenetic regulation exploring the biophysics of an epigenetic regulatory methyl-CpG binding protein MeCP2 whose disruption is causes the neurological disorder Rett Syndrome.
- Our interest in RNA structure and folding embraces RNA aptamers, small RNA molecules selected to bind to proteins and cells with high affinity as potential diagnostic tools or therapeutics. We are studying the structure and thermodynamics of aptamer – protein complexes in order to illuminate the principals of aptamer binding and perhaps build biologically efficacious aptamers.
- We are developing and utilizing a high-throughput method to map protein-protein interactions using amino acid side chain oxidation by the hydroxyl radical to measure solvent accessibility. The enabling technology for this project is a novel implementation of hydroxyl radical generation via the Fenton reaction. We are using this new approach to the assembly of proteins and the binding of small molecule therapeutics to their target proteins.
Selected Publications
Chapman, J.R., Paukner, M., Leser, M., Becker, C., Tang, K., Koide, S., Ueberheide, B., Brenowitz, M. (2023) Systematic Fe(II)-EDTA Method of Dose-Dependent Hydroxyl Radi-cal Generation for Protein Oxidative Footprinting, Analytical Chemistry, 95(50):18316-18325
Bou-Assaf, G.M., Budyak, I.L., Brenowitz, M., Day, E.S., Hayes, D., Hill, J., Majumdar, R., Ringhieri, P., Schuck. P., Lin, J.C. (2022) Best Practices for Aggregate Quantitation of An-tibody Therapeutics by Sedimentation Velocity Analytical Ultracentrifugation, J Pharm Sci. 111, 2121-2133
Sun, Y., Stransky, S., Aguilan, J., Koul, S., Garforth, S.J., Brenowitz, M., & Sidoli, S. (2021) High throughput and low bias DNA methylation and hydroxymethylation analysis by direct injection mass spectrometry, Analytica Chimica Acta, 1180, 338880
Dixit, U., Bhutoria, S., Wu, X., Qiu, L., Spira, M., Mathew, S., Harris, R., Adams, L.J, Cahill, S., Pathak, R., Prakash, R., Nguyen, M., Acharya, S.A., Brenowitz, M., Almo, S.C., Zou, X., Steven, A.C., Cowburn, D., Girvin, M., & Kalpana, G.V. (2021) INI1/SMARCB1 Rpt1 do-main mimics TAR RNA in binding to integrase 2 to facilitate HIV-1 replication, Nature Communications, 2021 May 12;12(1)
Bain, D.L., Brenowitz, M., Roberts, C.J. (2016) An Opportunity for Industry-Academia Partnership: Training the Next Generation of Industrial Researchers in Characterizing Higher Order Protein Structure, J. Pharmaceutical Sciences 105(12), 3483 - 3486
Khrapunov, S., Tao, Y., Cheng, H., Padlan, C., Harris, R., Galanopoulou, A.S., Greally, J.M., Girvin, M.E., Brenowitz, M. (2016) MeCP2 Binding Cooperativity Inhibits DNA Modification-Specific Recognition,Biochemistry 55(31), 4275 - 85
LoPiccolo, J., Kim, S.J., Shi, Y., Wu, B., Wu, H., Chait, B.T., Singer, R.H., Sali, A., Brenowitz, M., Bresnick, A.R., Backer, J.M. (2015) Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α Homodimer, J Biological Chemistry 290(51), 30, 390-30,405
Padlan, C.S., Malashkevich, V., Almo, S.C., Levy, M., Brenowitz, M. & Girvin, M.E. (2014) An RNA aptamer possessing a novel monovalent cation-mediated fold inhibits lysozyme catalysis by inhibiting the binding of long natural substrates, RNA, 20(4), 447-61
Chen, C., Mitra, S., Jonikas, M., Martin, J., Brenowitz, M., Laederach, A. Biophys J. (2013) Understanding the role of 3-dimensional topology in determining the folding intermediates of group 1 introns, Biophys J. 104(6), 1326-37