Mazitschek Lab

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Phone: 617-643-6286

Exploring and understanding biological systems at the molecular level with a tool set offered by modern chemistry is the common motif of my research interests. As a Chemical Biologist I find it intriguing to use small organic compounds, either derived from nature or by rational design, to study complex biological processes with a resolution that is neither offered by genetic nor biochemical approaches. Consequently the research in my lab is centered on the interface of biology and organic synthetic chemistry, including the synthesis of diversity-oriented-synthesis (DOS) derived libraries for biochemical and in vitro screening, the development of novel assay systems for high-throughput screening, as well as the development of small molecule tool compounds for target identification and imaging application.

Recent Publications

  • Yue H, Nowak RP, Overwijn D, Payne NC, Fischinger S, Atyeo C, Baden LR, Nilles EJ, Karlson EW, Yu XG, Li JZ, Alter G, Mazitschek R, Fischer ES Rapid 'mix and read' assay for scalable detection of SARS-CoV-2 antibodies in patient plasma. medRxiv. 2020;:ePub - PMID: 32909004 - PMCID: PMC7480056 - DOI: 10.1101/2020.09.01.20184101

  • Liston SD, Whitesell L, McLellan CA, Mazitschek R, Petraitis V, Petraitiene R, Kavaliauskas P, Walsh TJ, Cowen LE Antifungal activity of gepinacin-scaffold GPI anchor biosynthesis inhibitors with improved metabolic stability. Antimicrob Agents Chemother. 2020;:ePub - PMID: 32661007 - PMCID: PMC7508603 - DOI: 10.1128/AAC.00899-20

  • Badr CE, da Hora CC, Kirov AB, Tabet E, Amante R, Maksoud S, Nibbs AE, Fitzsimons E, Boukhali M, Chen JW, Chiu NHL, Nakano I, Haas W, Mazitschek R, Tannous BA Obtusaquinone is a cysteine modifying compound that targets Keap1 for degradation. ACS Chem Biol. 2020;15(6):1445-1454 - PMID: 32338864 - DOI: 10.1021/acschembio.0c00104

  • Kim Y, Sundrud MS, Zhou C, Edenius M, Zocco D, Powers K, Zhang M, Mazitschek R, Rao A, Yeo CY, Noss EH, Brenner MB, Whitman M, Keller TL Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells. Proc Natl Acad Sci U S A. 2020;117(16):8900-8911 - PMID: 32253314 - PMCID: PMC7183223 - DOI: 10.1073/pnas.1913788117

  • Zhao WN, Hylton NK, Wang J, Chindavong PS, Alural B, Kurtser I, Subramanian A, Mazitschek R, Perlis RH, Haggarty SJ Activation of WNT and CREB signaling pathways in human neuronal cells in response to the Omega-3 fatty acid docosahexaenoic acid (DHA). Mol Cell Neurosci. 2019;99:103386 - PMID: 31202891 - PMCID: PMC7001743 - DOI: 10.1016/j.mcn.2019.06.006

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Research projects

One major focus in my group is in the development of subtype specific modulators of chromatin modifying enzymes, such as histone deacetylase (HDAC) inhibitors. HDACs have originally been discovered as chromatin modifying enzymes, however, recent research suggests that regulation of non-histone proteins by acetylation is more abundant than originally anticipated and comparable to other posttranslational modifications. The development of HDAC inhibitors (as tool compounds or as drug) has paid little attention to subtype specificity, which is limiting the applicability of these compounds. Our goal is it to understand the features that convey selectivity and to develop tools to selectively study the function of HDACs isoforms (in particular class II enzymes) in in vivo and in vivo systems.

In addition I do have a strong interest in dieseases that are neglected by industrial research due to the lack of financial interest. In particular my group has been focusing on the discovery of novel antimalarials and the identification of previously untargeted pathways that are vital to the Plasmodium parasite and suitable for chemotherapeutic intervention. The identification of the molecular target(s) of active compounds will not only allow to study their underlying biology in P. falciparum but also accelerate the development of novel medicines.

News

2019-11-25: Kritika Singh (Mazitschek Lab), a bioengineering and chemistry student at Northeastern who has dedicated herself to tackling global health issues, has been named a 2020 Rhodes Scholar, considered the most prestigious academic honor for U.S. college students. Congratulations, Kritika!
2017-04-17: Ralph Mazitschek, PhD has received the Young Mentor Award from Harvard Medical School (HMS). The award was established in 2005 to recognize faculty who are still in the early stages of their career, but are devoting time to mentor others. Congratulations, Ralph!
2016-12-02: Ralph Mazitschek, PhD received new patent for Compounds for Treating Infectious Diseases. Susan Lindquist, Catherine McLellan and Luke Whitesell, MD were co-inventors.
2011-10-27: MIT News features work of Mazitschek Group on microarray identification of small molecules that enhance synaptogenesis. (pdf)