Chemistry Department
Colleen Connely headshot

Colleen Connelly

Job Title
Assistant Professor of Chemistry
Wold Center 218

Areas of expertise

Chemical Biology, RNA Biochemistry, Organic Chemistry

Research interests

Our research aims to interface organic chemistry and biology to investigate and manipulate RNA structure and function. Modern biology embraces an expanded role for RNA with diverse RNAs having broad functions in regulating gene expression and other biological processes. Furthermore, a large number of noncoding RNAs are associated with human diseases, providing a wealth of previously unrecognized targets for understanding and treating disease. Many of these RNAs adopt discrete structures that are important for their pivotal roles in biology. Often, RNA function can be attributed to its ability to undergo structural changes in response to cellular stimuli. Understanding the factors that modulate these changes is key to assessing the role that RNA structure plays in governing regulatory events. Our research program aims to probe RNA function by investigating and manipulating conformational changes in specific RNAs. In particular, we are exploring the role that alternative structures play in the processing of microRNAs (miRNAs), a class of gene regulators that have been implicated in cancer, cardiovascular disease, and immune disorders.

In addition to their effects on biological function, structures in RNA are attractive targets for organic molecules. Despite the development of powerful techniques to analyze RNA structure and function, our ability to develop probes that bind to and perturb the function of RNA lags behind. Our group further aims to identify chemical probes for specific RNAs in order to answer questions about how structure affects their roles in disease. Specifically, we are exploring the ability of small molecules to modulate the structure and processing of precursor microRNAs to further understand their regulation in cancer. Through these projects, students in my lab will have the opportunity to explore multidisciplinary research combining biochemistry, organic chemistry, molecular biology, and biophysical techniques.

Teaching interests

CHM 231 Organic Chemistry I & Lab
CHM 232L Organic Chemistry II Lab
BCH 335 Survey of Biochemistry
BCH 382L Biochemistry: Structure and Catalysis Lab

I teach courses for our Chemistry and Biochemistry majors as well as non-majors pursuing various science-based careers. In my courses, I try to create an environment where chemistry is accessible to all students.

Additional media

Publications & Recent Funding

  • Publications
    • Emanuelson, C.; Ankenbruck, N.; Kumbhare, R.; Thomas, M.; Connelly, C.; Baktash, Y.; Randall, G.; Deiters, A. Transcriptional Inhibition of MicroRNA miR-122 by Small Molecules Reduces Hepatitis C Virus Replication in Liver Cells. J Med Chem. 2022, 65, 16338.
    • Balaratnam, S.; Rhodes, C.; Bume, D. D.; Connelly, C. M.: Lai, C. C.; Kelley, J. A.; Yazdani, K.; Homan, P. J.; Incarnato, D.; Numata, T.; Schneekloth, J. S. Jr., A chemical probe based on the PreQ1 metabolite enables transcriptome-wide mapping of binding sites. Nat Commun. 2021, 12, 5856.
    • Tran, B.; Pichling, P.; Tenney, L.; Connelly, C. M.; Moon, M. H.; Ferré-D’Amaré, A. R.; Schneekloth, J. S.; Jones, C. P., Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design. Cell Chem. Biol. 2020, 27, 1241.
    • Calabrese, D. R.;* Connelly, C. M.;* Schneekloth, J. S., Ligand-observed NMR techniques to probe RNA-small molecule interactions. Methods Enzymol. 2019, 623, 131.
    • Connelly, C. M.;* Numata, T.;* Boer, R. E.; Moon, M. H.; Sinniah, R. S.; Barchi, J. J.; Ferré-D’Amaré, A. R.; Schneekloth, J. S., Synthetic Ligands for PreQ1 Riboswitches Provide Structural and Mechanistic Insights into Targeting RNA Tertiary Structure. Nat. Commun. 2019, 10, 1501.
    • Naro, Y.; Ankenbruck, N.; Thomas, M.; Tivon, Y.; Connelly, C. M.; Gardner, L.; Deiters, A., Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan. J. Med. Chem. 2018, 61, 5900.
    • Calabrese, D. R.; Zlotkowski, K.; Alden, S.; Hewitt, W. M.; Connelly, C. M.; Wilson, R.; Gaikwad S.; Chen, L.; Guha, R.; Thomas, C. J.; Mock, B. A.; Schneekloth, J. S., Characterization of Clinically Used Oral Antiseptics as Quadruplex-Binding Ligands. Nucleic Acids Res., 2018, 46, 2722.
    • Connelly, C. M.; Boer, R. E.; Moon, M. H.; Gareiss, P.; Schneekloth, J. S., Discovery of Inhibitors of MicroRNA-21 Processing Using Small Molecule Microarrays. ACS Chem. Biol., 2017, 12, 435.
    • Connelly, C. M.; Abulwerdi, F. A.; Schneekloth, J. S., Discovery of RNA Binding Small Molecules Using Small Molecule Microarrays. In Small Molecule Microarrays: Methods and Protocols, Uttamchandani, M.; Yao, S. Q., Eds. Springer New York: New York, NY, 2017, 1518, 157.
    • Connelly, C. M.; Moon, M. H.; Schneekloth, J. S., The Emerging Role of RNA as a Therapeutic Target for Small Molecules. Cell Chem. Biol., 2016, 23, 1077.
    • Naro, Y.; Thomas, M.; Stephens, M. D.; Connelly, C. M.; Deiters, A. Aryl amide small-molecule inhibitors of microRNA miR-21 function. Bioorg. Med. Chem. Lett. 2015, 25, 4793.
    • Enamorado, M. F.; Connelly, C. M.; Deiters, A.; Comins, D. L. A concise synthesis of the Lycopodium alkaloid cermizine D. Tetrahedron Lett. 2015, 56, 3683.
    • Vonlanthen, M.; Connelly, C. M.; Deiters, A.; Linden, A.; Finney, N. S. Thiourea-based fluorescent chemosensors for aqueous metal ion detection and cellular imaging. J. Org. Chem. 2014, 79, 6054.
    • Connelly, C. M.; Deiters, A. "Control of Oncogenic miRNA Function by Light-activated miRNA Antagomirs", In Methods in Molecular Biology: Cancer Cell Signaling, Ed.: M. Robles-Flores, Springer 2014, 1165, 99.
    • Connelly, C. M.; Deiters, A. "Identification of Inhibitors of microRNA Function from Small Molecule Screens", In Methods in Molecular Biology: MicroRNA Maturation, Ed.: C. Arenz, Springer 2014, 1095, 147.
    • Connelly, C. M.; Deiters, A. "Cellular MicroRNA Sensors Based on Luciferase Reporters", In Methods in Molecular Biology: MicroRNA Maturation, Ed.: C. Arenz, Springer 2014, 1095, 135.
      Connelly, C. M.; Deiters, A. "Small-Molecule Regulation of microRNA Function", In MicroRNA in Cancer, Ed.: S. Alahari, Springer 2013, 119.
    • Connelly, C. M.; Uprety, R.; Hemphill, J.; Deiters, A. Spatiotemporal Control of MicroRNA Function using Light-Activated Antagomirs. Mol. BioSyst. 2012, 8, 2987.
    • Connelly, C. M.; Thomas, M.; Deiters, A. High-Throughput Luciferase Reporter Assay for Small Molecule Inhibitors of MicroRNA Function. J.Biomol. Screen. 2012, 17, 822.
    • Young, D. D.;* Connelly, C. M.;* Grohmann, C.; Deiters, A. Small Molecule Modifiers of MicroRNA miRNA-122 Function for the Treatment of Hepatitis C Virus Infection and Hepatocellular Carcinoma. J. Am. Chem. Soc. 2010, 132, 7976.
  • Recent Funding
    • “A Fluorescence-Based Approach to Investigate Structurally Dynamic Precursor MicroRNAs,” Community Foundation for the Greater Capital Region’s Bender Scientific Fund, April 2020, Funded at $11,216.

Academic credentials

B.S., University of North Carolina Wilmington; Ph.D., North Carolina State University; Postdoc, National Cancer Institute