murelli

Murelli, Ryan

Dean, Chemistry and Biochemistry Department, Brooklyn College, The City University of New York

Academic Appointments:

2020-present   Joint Appointment, PhD Program in Biochemistry, Graduate Center of CUNY
2019-present    Professor, Chemistry and Biochemistry Department, 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:

3. 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.

1. 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: 

Agency: National Institutes of Health, NIGMS (SC1)
Period: 05/01/2020-04/31/2024
Role: Principal Investigator
Title: Development and Exploitation of New Synthetic Strategies for Tropolones
($1,533,665.00)

Agency: National Institutes of Health, NIAID (RO1)
Period: 12/01/2015-11/31/2020
Role: Collaborator under subcontract [PI, John Tavis]
Title: Optimization of alpha-hydroxytropolones as novel inhibitors of the HBV RNaseH
($658,553 of $2,740,000)

Completed Research Support:

Agency: National Institutes of Health, NIGMS (SC1)
Period: 04/01/2015-5/31/2020
Title: Synthetic and biological studies of α-Hydroxytropolones
($1,558,600)

Agency: PSC CUNY Program
Period: 06/01/2012-7/31/2013
Title: Synthesis of 7-hydroxytropolones
Role: Principal Investigator
($3,500)

Agency: National Institutes of Health, NIGMS (SC2)
Grant number: 65420-00 42
Period: 04/01/2012-11/31/2015
Title: Synthetic and biological studies of antitubercular natural products
Role: Principal Investigator
($471,000)

Agency: Alfred P. Sloan Foundation, CUNY
Title: Alfred P. Sloan Foundation CUNY Junior Faculty Award in Science and Engineering
Period: 03/01/2015-02/31/2016
($50,000)