Faculty Assistant

Heather Krupinski
Frick Laboratory, 128

Research Focus

Our current understanding of nucleic acid biology indicates that RNA plays a number of diverse roles in cellular processes ranging from protein translation and gene regulation to metabolite sensing and adaptive immunity. Concomitant with this functional diversity, is the rich chemical diversity of cellular RNA. To date, over 100 structurally distinct chemical modifications have been found, including both enzymatic and non-enzymatic modifications of the canonical ribonucleotides; however, there is a major gap in our understanding of how these chemical modifications impact RNA function.

Our goal is to decipher the chemical complexity of cellular RNA. Towards this end, we are developing and employing novel approaches integrating chemistry and biology to investigate the functional significance of RNA modifications and the interplay of RNA chemistry with cellular mechanisms regulating RNA function and integrity. Our studies will rely heavily upon synthetic and chemoenzymatic strategies for generating modified nucleic acids, chemical proteomics, and quantitative cellular imaging, and aim to reveal fundamental biological mechanisms maintaining cellular homeostasis.


Research Areas
Chemical Biology

NSF CAREER Award (2019)

Sloan Research Fellowship (2019)

Sidney Kimmel Foundation Scholar Award (2017)

Damon Runyon Dale F. Frey Award for Breakthrough Scientists (2016)

Revson Foundation Fellowship in Biomedical Science (2014)

Damon Runyon Cancer Research Foundation Postdoctoral Fellowship (2012)

Selected Recent Publications

"YTHDF2 Recognition of N1-Methyladenosine (m1A)-Modified RNA Is Associated with Transcript Destabilization" Seo, K.W.; Kleiner, R.E. ACS Chem Biol. 2019 Dec 12. doi: 10.1021/acschembio.9b00655. [Epub ahead of print]

"In vitro selection with a site-specifically modified RNA library reveals the binding preferences of N6-methyladenosine (m6A) reader proteins" Arguello, A. E.; Leach, R. W.; Kleiner, R. E. Biochemistry 2019 58, 3386-3395

"A Metabolic Engineering Approach to Incorporate Modified Pyrimidine Nucleosides into Cellular RNA" Zhang Y.; Kleiner R.E. J. Am Chem Soc. 2019 DOI: 10.1021/jacs.8b11449

“RNA Chemical Proteomics Reveals the N6-Methyladenosine(m6A)-Regulated Protein-RNA Interactome” Arguello, A. E.; DeLiberto, A. N.; Kleiner, R. E. J. Am. Chem. Soc. 2017 DOI: 10.1021/jacs.7b09213

“A Chemical Proteomics Approach to Reveal Direct Protein-Protein Interactions in Living Cells” Kleiner, R. E.; Hang, L. E.; Molloy, K. R.; Chait, B. T.; Kapoor, T. M. Cell Chem. Biol. 2017 DOI: 10.1016/j.chembiol.2017.10.001.

“Reading the RNA Code” Kleiner, R. E. Biochemistry 2017 DOI:10.1021/acs.biochem.7b00866.

“Structural and Biochemical Basis for Intracellular Kinase Inhibition by Src-specific Peptidic Macrocycles” Aleem, S. U.*; Georghiou, G.*; Kleiner, R. E.*; Guja, K. E.; Craddock, B. P.; Lyczek, A.; Chan, A. I.; Garcia-Diaz, M.; Miller, W. T.; Liu, D. R.; Seeliger, M. A.; Cell Chem. Biol. 2016 23, 1103-1112.

“Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends” Ti, S. C.; Pamula, M. C.; Howes, S. C.; Duellberg, C.; Cade, N. I.; Kleiner, R. E.; Forth, S.; Surrey, T.; Nogales, E.; Kapoor, T. M. Dev. Cell 2016 4, 72-84.

“Chemical Proteomics Reveals a γH2AX-53BP1 Interaction in the DNA Damage Response” Kleiner, R. E.; Verma, P.; Molloy, K. R.; Chait, B. T.; Kapoor, T. M. Nat. Chem. Biol. 2015 10, 807-814.

“Anti-Diabetic Activity of Insulin-Degrading Enzyme Inhibitors Mediated by Multiple Hormones” Maianti, J. P.; McFedries, A.; Foda, Z. H.; Kleiner, R. E.; Du, X.; Lessring, M.; Tang, W.; Charron, M. J.; Seeliger, M. A.; Saghatelian, A.; Liu, D. R.; Nature 2014 511,

“Bumping Up Kinase Activity with an ATP-Derived Neo-Substrate” Kleiner, R. E.; Kapoor, T. M. Cell 2013 154, 716-718.

“Site-Specific Chemistry on the Microtubule Polymer” Kleiner, R. E.; Ti, S. C.; Kapoor, T. M. J. Am. Chem. Soc. 2013 135, 12520-12523.

“Highly specific, bisubstrate-competitive Src inhibitors from DNA-templated macrocycles” Georghiou, G.*; Kleiner, R. E.*; Pulkoski-Gross, M.; Liu, D. R.; Seeliger, M. A. Nat. Chem. Biol. 2012 8, 366-374.

“Small-Molecule Discovery from DNA-Encoded Chemical Libraries” Kleiner, R. E.*; Dumelin, C. E.*; Liu, D. R. Chem. Soc. Rev. 2011 40, 5707-5717.

“In Vitro Selection of a DNA-Templated Small-Molecule Library Reveals a Class of Macrocyclic Kinase Inhibitors” Kleiner, R. E.; Dumelin, C. E.; Tiu, G. C.; Sakurai, K.; Liu, D. R. J. Am. Chem. Soc. 2010 132, 11779-11791.

“An In Vitro Translation, Selection and Amplification System for Peptide Nucleic Acid” Brudno, Y.; Birnbaum, M. E.; Kleiner, R. E.; Liu, D. R. Nat. Chem. Biol. 2010 6, 148-155.

“DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes” Kleiner, R. E.; Brudno, Y.; Birnbaum, M. E.; Liu, D. R. J. Am. Chem. Soc. 2008 130, 4646-4659.

“An Intein-Based Genetic Selection Enables Construction of a High-Quality Library of Binary Patterned De Novo Sequences” Bradley, L. H.; Kleiner, R. E.; Wang, A. F.; Hecht, M. H.; Wood, D.W. Protein Eng. Des. Sel. 2005 18, 201-207.