Kappel, Kalli

Biochemistry

Short Biography

Dr. Kappel received her B.S. in Physics from the University of California San Diego, where she worked with Professor Andrew McCammon to study protein dynamics and protein-ligand interactions using computational approaches. She received her Ph.D. in Biophysics from Stanford University, where she focused on developing computational methods to predict RNA structures and RNA-protein interactions with Professor Rhiju Das. Her graduate work was supported by an NSF Graduate Research Fellowship and a Gabilan Stanford Graduate Fellowship. Subsequently, as an HHMI Hanna Gray Postdoctoral Fellow and Schmidt Science Fellow at the Broad Institute of MIT and Harvard, she developed and applied a high-throughput experimental approach to characterize the relationships between protein sequences and nuclear condensate formation. Dr. Kappel will join the UCLA faculty in July 2025. Her lab will focus on developing predictive sequence-structure-function models of RNA, proteins, and their interactions by combining high-throughput experiments, machine learning, and computational biophysical methods.

Research Interests

The Kappel Lab is focused on understanding how RNA and protein sequences encode molecular and cellular function. We’re especially interested in elucidating how RNA binding proteins control all aspects of RNA metabolism and function. We take an integrated experimental and computational approach. Specifically:

(1) We develop high-throughput experiments to map multiscale structures — from molecular conformations, to formation of higher-order assemblies, to subcellular localization — and function for large libraries of protein and RNA sequences, focusing especially on measuring these relationships in human cells. We primarily utilize a variety of imaging and sequencing approaches.

(2) We use machine learning and computational biophysical approaches to learn and extrapolate from our large-scale data.

Our goal is to develop predictive sequence-structure-function models, and to harness these models to gain novel biological insights, to understand how mutations cause disease, and to design functional protein and RNA sequences.

 

Honors & Awards

  • HHMI Hanna H. Gray Fellowship, 2021-2029
  • Schmidt Science Fellowship, 2020-2021
  • ACS Chemical Computing Group Excellence Award for Graduate Students, 2019
  • Biophysical Society Student Research Achievement Award, 2017
  • NSF Graduate Research Fellowship, 2014-2019
  • Gabilan Stanford Graduate Fellowship, 2014-2019
  • Silagi Award for Undergraduate Excellence, 2014
  • Shang-Keng Ma Award, UCSD, 2014
  • Ledell Family Endowed Research Scholarship, 2013
  • Amgen Scholars Fellowship, Stanford University, 2013
  • NYSTEM Summer Research Fellowship, Columbia University, 2012
  • UC San Diego Regents Scholarship, 2010-2014

Representative Publications

For a full list, please see here.

 

  • Hirano S*, Kappel K*, Altae-Tran H, Faure G, Wilkinson ME, Kannan S, Demircioglu FE, Yan R, Shiozaki M, Yu Z, Makarova KS, Koonin EV, Macrae RK, Zhang F. Structure of the OMEGA nickase IsrB in complex with ωRNA and target DNA. (2022). doi: 10.1038/s41586-022-05324-6
  • Su Z*, Zhang K*, Kappel K*, Li S, Palo MZ, Pintilie GD, Rangan R, Luo B, Wei Y, Das R, Chiu W. Cryo-EM structures of full-length Tetrahymena ribozyme at 3.1 Å resolution. (2021). doi: 10.1038/s41586-021-03803-w
  • Kappel K*, Zhang K*, Su Z*, Kladwang W, Li S, Pintilie G, Topkar VV, Rangan R, Zheludev IN, Yesselman JD, Chiu W, Das R. Accelerated cryo-EM-guided determination of three-dimensional RNA-only structures. Nature Methods. (2020). doi: 10.1038/s41592-020-0878-9
  • Zhang K*, Li S*, Kappel K*, Pintilie G, Su Z, Mou TC, Schmid MF, Das R, Chiu W. Cryo-EM Structure of a 40-kDa SAM-IV Riboswitch RNA at 3.7 Å Resolution. Nature Communications. (2019). 10(1): 5511. doi: 10.1038/s41467-019-13494-7
  • Kappel K, Jarmoskaite I, Vaidyanathan PP, Greenleaf WJ, Herschlag D, Das R. Blind tests of RNA-protein binding affinity prediction. PNAS. (2019). 116: 8336-8341; doi: 10.1073/pnas.1819047116
  • Kappel K, Das R. Sampling native-like structures of RNA-protein complexes through Rosetta folding and docking. Structure. (2019). 27: 140-151; doi: 10.1016/j.str.2018.10.001
  • Kappel K, Liu S, Larsen KP, Skiniotis G, Puglisi EV, Puglisi JD, Zhou ZH, Zhao R, Das R. De novo computational RNA modeling into cryo-EM maps of large ribonucleoprotein complexes. Nature Methods. (2018). 15: 947–954; doi: 10.1038/s41592-018-0172-2
  • Parks JW*, Kappel K*, Das R, Stone MD. Single molecule FRET-Rosetta reveals RNA structural rearrangements during human telomerase catalysis. RNA. (2017). 23(2): 175-188. doi: 10.1261/rna.058743.116
  • Kappel K, Miao Y, McCammon JA. Accelerated molecular dynamics simulations of ligand binding to a muscarinic G-protein coupled receptor. Quarterly Review of Biophysics. (2015). 48(4): 479-87; doi: 10.1017/S0033583515000153
  • Kappel K, Wereszczynski J, Clubb RT, McCammon JA. The binding mechanism, multiple binding modes, and allosteric regulation of Staphylococcus aureus Sortase A probed by molecular dynamics simulations. Protein Science. (2012). 21: 1858-1871; doi: 10.1002/pro.2168