murelli

Murelli, Ryan

Academic Appointments:

2020-present   Joint Appointment, PhD Program in Biochemistry, Graduate Center of CUNY
2019-present   Professor, Department of Chemistry, Brooklyn College
2017-2019       Associate Professor, Department of Chemistry, Brooklyn College
2017-present  Organic Sub-discipline Chair in PhD Program in Chemistry
2010-present   Joint Appointment, PhD Program in Chemistry, Graduate Center of CUNY
2010-2017      Assistant Professor, Department of Chemistry, Brooklyn College

Degrees:

BA      Chemistry                               Hamilton College, Clinton, NY
PhD     Organic Chemistry              Boston College, Chestnut Hill, MA

Research Focus:

Our group is a synthetic organic chemistry lab whose members develop organic reactions and multistep synthetic strategies towards various molecular targets, and then use these strategies in a broad range of projects that represent both fundamental and translational research.  Two distinct but complementary research niches have emerged from our synthetic organic chemistry work to date based around developing and exploiting oxidopyrylium [5+2] cycloaddition reactions, as well as developing new synthetic strategies to access tropone-containing molecules.  These studies have been particularly valuable in accessing a class of metalloenzyme-binding fragments called 7-hydroxytropolones (or a-hydroxytropolones, which we often abbreviate as aHTs).  Our work on aHTs has led to dozens of collaborations from labs all around the world, which have allowed us to study this chemotype in depth.  Our most active collaborative network, which includes BC colleague Emilio Gallicchio as well as scientists from the National Cancer Institute and Saint Louis University School of Medicine, is interested in studying and optimizing aHTs as inhibitors of viral nuclease enzymes and the impact of this inhibition on antiviral activity against several viruses including HIV and herpes simplex virus, as well as the oncoviruses hepatitis B virus and Kaposi’s sarcoma-associated herpesvirus.  Repurposing efforts have also led to inroads against other pathogens such as Cryptococcus neoformans, the major causative agent of fungal meningitis worldwide.

Selected Publications:

  1. Li, Q.; Lomonosova, E.; Donlin, M. J.; Cao, F.; O’Dea, A.; Milleson, B.; Berkowitz, A. J.; Baucom, J-C.; Stasiak, J. P.;Schiavone, D. V.; Abdelmessih, R. G.; Lyubimova, A.; Fraboni, A. J.; Bejcek, L.P.; Villa, J. A.; Gallicchio, E.; Murelli, R. P.*; Tavis, J. E.* “Amide-containing α-hydroxytropolones as inhibitors of hepatitis B virus replication” Antiviral Res. 2020, 177, 104777.
  2. Agyemang, N. B.; Kukla, C. R.; Edwards, T. C.; Li, Q.; Langen, M. K.; Schaal, A.; Franson, A. D.; Gazquez Casals, A.; Donald, K. A.; Yu, A. J.; Donlin, M. J.; Morrison, L. A.; Tavis, J. E.; Murelli, R. P.* “Divergent Synthesis of a Thiolate-Based α-Hydroxytropolone Library with a Dynamic Bioactivity Profile” RSC Advances, 2019, 9, 34227.
  3. Hirsch, D. R.; Schiavone, D. V.; Berkowitz, A. J.; Morrison, L. A.; Masaoka, T.; Wilson, J. A.; Lomonosova, E.; Zhao, H.; Patel, B. S.; Dalta, S. H.; Majidi, S. J.; Pal, R.; K.; Gallicchio, E.; Tang, L.; Tavis, J. E.; Le Grice, S. F. J.; Beutler, J. A.; Murelli, R. P.* “Synthesis and Biological Assessment of 3,7-Dihydroxytropolones” Biomol. Chem. 2018, 16, 62-69
  4. Miller, J. T.; Zhao, H.; Masaoka, T.; Varnado, B.; Cornejo Castro, E. M.; Marshall, V. A.; Kouhestani, K.; Lynn, A. Y.; Aron, K. E.; Xia, A.; Beutler, J. A.; Hirsch, D. R.**; Tang, L.; Whitby, D.; Murelli, R. P.; Le Grice, S. F. J.* “Sensitivity of the C-Terminal Nuclease Domain of Kaposi’s Sarcoma-Associated Herpesvirus ORF29 to Two Classes of Active Site Ligands” Agents. Chemother. 2018, 62, e00233-18.
  5. D’Erasmo, M. P.; Murelli, R. P.* “Fluorous-Phase Approach to α-Hydroxtropolone Synthesis” Org. Chem. 2018, 83, 1478.

 

Patent Applications:

 

  1. Donlin, M. J.; Tavis, J. E.; Murelli, R.; Meyers, M. J. “Preparation of substituted cycloheptatrienones as antifungal compounds” PCT Int. Appli. (2017) No. WO 2017-184752.
  2. Tavis, J. E; Morrison, L. A.; Murelli, R. P. “Preparation of hydroxylated tropolone inhibitorsof nucleotidyl transferases in treatment of herpesvirus and hepatitis B” PCT Int. Appl. (2016) No. WO 2016-201243.
  3. Spiegel, D.; Murelli, R.; Zhang, A. “Chimeric Small Molecules that Recruit Antibodies to Cancer Cells” PCT Int. Appl. (2009) No. WO 2009-US2857.  Patent No. WO  2009139863.

Active Research Support: 

(May 2020 – Apr. 2024) National Institutes of Health, NIGMS (SC1)  “Development and Exploitation of New Synthetic Strategies for Tropolones ” ($1,533,665.00) Role: PI

(Dec. 2015 – Nov. 2020) National Institutes of Health, NIAID (RO1) “Optimization of alpha-hydroxytropolones as novel inhibitors of the HBV RNaseH” ($658,553 of $2,740,000) [PI, John Tavis] Role: Collaborator under subcontract

Completed Research Support:

(Apr. 2015 – May 2020) National Institutes of Health, NIGMS (SC1) “Synthetic and biological studies of α-Hydroxytropolones”($1,558,600)

(July 2012 – July 2013) PSC CUNY Program (65420-00 42) “Synthesis of 7-hydroxytropolones” ($3,500) Role: PI

(Apr. 2012 – Nov. 2015) National Institutes of Health, NIGMS (SC2) “Synthetic and biological studies of antitubercular natural products” ($471,000) Role: PI

(March 2015 – February 2016) Alfred P. Sloan Foundation CUNY Junior Faculty Award in Science and Engineering ($50,000)