Honors & Awards

  • School of Medicine Dean's Postdoctoral Fellowship, Stanford University (2022)
  • DiGenova Postdoc Seed Grant, Stanford University (2021)
  • Dissertation Year Fellowship, UCLA (2017)
  • Whitcome Fellow, UCLA (2015 - 2016)
  • Bioengineering Department Fellowship, UCLA (2013)
  • Panasonic Scholarship, Peking University (2010)
  • Kwang-Hua Scholarship, Peking University (2008)

Professional Education

  • Doctor of Philosophy, University of California Los Angeles (2019)
  • Ph.D., University of California, Los Angeles, Bioengineering (2019)
  • M.S., University of California, Los Angeles, Mechanical Engineering (2013)
  • B.S., Peking University, Electrical Engineering and Computer Science (2011)

Stanford Advisors


  • Otto O. Yang, Ke Ding, Jan Mrazek, Z. Hong Zhou. "United States Patent 20200255488A1 Vault Particles Having a Modified R8 Flexible Region", University of California, Aug 13, 2020

All Publications

  • Dispatched uses Na+ flux to power release of lipid-modified Hedgehog. Nature Wang, Q., Asarnow, D. E., Ding, K., Mann, R. K., Hatakeyama, J., Zhang, Y., Ma, Y., Cheng, Y., Beachy, P. A. 2021


    The Dispatched protein, which is related to the NPC1 and PTCH1 cholesterol transporters1,2 and to H+-driven transporters of the RND family3,4, enables tissue-patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly-localized sites of embryonic expression5-10. Here we determine a cryo-electron microscopy structure of the mouse protein Dispatched homologue 1 (DISP1), revealing three Na+ ions coordinated within a channel that traverses its transmembrane domain. We find that the rate of Hedgehog export is dependent on the Na+ gradient across the plasma membrane. The transmembrane channel and Na+ binding are disrupted in DISP1-NNN, a variant with asparagine substitutions for three intramembrane aspartateresidues that each coordinate and neutralize the charge of one of the three Na+ ions. DISP1-NNN and variants that disrupt single Na+ sites retain binding to, but are impaired in export of the lipid-modified Hedgehog protein to the SCUBE2 acceptor. Interaction of the amino-terminalsignallingdomain of theSonic hedgehog protein(ShhN) with DISP1 occurs via an extensive buried surface area and contacts with an extended furin-cleaved DISP1 arm. Variability analysis reveals that ShhN binding is restricted to one extreme of a continuous series of DISP1 conformations. The bound and unbound DISP1 conformations display distinct Na+-site occupancies, which suggests a mechanism by which transmembrane Na+ flux may power extraction of the lipid-linked Hedgehog signal from the membrane. Na+-coordinating residues in DISP1 are conserved in PTCH1 and other metazoan RND family members, suggesting that Na+ flux powers their conformationally driven activities.

    View details for DOI 10.1038/s41586-021-03996-0

    View details for PubMedID 34707294

  • Action of a minimal contractile bactericidal nanomachine NATURE Ge, P., Scholl, D., Prokhorov, N. S., Avaylon, J., Shneider, M. M., Browning, C., Buth, S. A., Plattner, M., Chakraborty, U., Ding, K., Leiman, P. G., Miller, J. F., Zhou, Z. 2020; 580 (7805): 658-+


    R-type bacteriocins are minimal contractile nanomachines that hold promise as precision antibiotics1-4. Each bactericidal complex uses a collar to bridge a hollow tube with a contractile sheath loaded in a metastable state by a baseplate scaffold1,2. Fine-tuning of such nucleic acid-free protein machines for precision medicine calls for an atomic description of the entire complex and contraction mechanism, which is not available from baseplate structures of the (DNA-containing) T4 bacteriophage5. Here we report the atomic model of the complete R2 pyocin in its pre-contraction and post-contraction states, each containing 384 subunits of 11 unique atomic models of 10 gene products. Comparison of these structures suggests the following sequence of events during pyocin contraction: tail fibres trigger lateral dissociation of baseplate triplexes; the dissociation then initiates a cascade of events leading to sheath contraction; and this contraction converts chemical energy into mechanical force to drive the iron-tipped tube across the bacterial cell surface, killing the bacterium.

    View details for DOI 10.1038/s41586-020-2186-z

    View details for Web of Science ID 000529600500018

    View details for PubMedID 32350467

    View details for PubMedCentralID PMC7513463

  • In situ structures of RNA-dependent RNA polymerase inside bluetongue virus before and after uncoating PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA He, Y., Shivakoti, S., Ding, K., Cui, Y., Roy, P., Zhou, Z. 2019; 116 (33): 16535–40


    Bluetongue virus (BTV), a major threat to livestock, is a multilayered, nonturreted member of the Reoviridae, a family of segmented dsRNA viruses characterized by endogenous RNA transcription through an RNA-dependent RNA polymerase (RdRp). To date, the structure of BTV RdRp has been unknown, limiting our mechanistic understanding of BTV transcription and hindering rational drug design effort targeting this essential enzyme. Here, we report the in situ structures of BTV RdRp VP1 in both the triple-layered virion and double-layered core, as determined by cryo-electron microscopy (cryoEM) and subparticle reconstruction. BTV RdRp has 2 unique motifs not found in other viral RdRps: a fingernail, attached to the conserved fingers subdomain, and a bundle of 3 helices: 1 from the palm subdomain and 2 from the N-terminal domain. BTV RdRp VP1 is anchored to the inner surface of the capsid shell via 5 asymmetrically arranged N termini of the inner capsid shell protein VP3A around the 5-fold axis. The structural changes of RdRp VP1 and associated capsid shell proteins between BTV virions and cores suggest that the detachment of the outer capsid proteins VP2 and VP5 during viral entry induces both global movements of the inner capsid shell and local conformational changes of the N-terminal latch helix (residues 34 to 51) of 1 inner capsid shell protein VP3A, priming RdRp VP1 within the capsid for transcription. Understanding this mechanism in BTV also provides general insights into RdRp activation and regulation during viral entry of other multilayered, nonturreted dsRNA viruses.

    View details for DOI 10.1073/pnas.1905849116

    View details for Web of Science ID 000481404300060

    View details for PubMedID 31350350

    View details for PubMedCentralID PMC6697807

  • In situ structures of rotavirus polymerase in action and mechanism of mRNA transcription and release NATURE COMMUNICATIONS Ding, K., Celma, C. C., Zhang, X., Chang, T., Shen, W., Atanasov, I., Roy, P., Zhou, Z. 2019; 10: 2216


    Transcribing and replicating a double-stranded genome require protein modules to unwind, transcribe/replicate nucleic acid substrates, and release products. Here we present in situ cryo-electron microscopy structures of rotavirus dsRNA-dependent RNA polymerase (RdRp) in two states pertaining to transcription. In addition to the previously discovered universal "hand-shaped" polymerase core domain shared by DNA polymerases and telomerases, our results show the function of N- and C-terminal domains of RdRp: the former opens the genome duplex to isolate the template strand; the latter splits the emerging template-transcript hybrid, guides genome reannealing to form a transcription bubble, and opens a capsid shell protein (CSP) to release the transcript. These two "helicase" domains also extensively interact with CSP, which has a switchable N-terminal helix that, like cellular transcriptional factors, either inhibits or promotes RdRp activity. The in situ structures of RdRp, CSP, and RNA in action inform mechanisms of not only transcription, but also replication.

    View details for DOI 10.1038/s41467-019-10236-7

    View details for Web of Science ID 000468174600016

    View details for PubMedID 31101900

    View details for PubMedCentralID PMC6525196

  • In Situ Structures of the Polymerase Complex and RNA Genome Show How Aquareovirus Transcription Machineries Respond to Uncoating JOURNAL OF VIROLOGY Ding, K., Nguyen, L., Zhou, Z. 2018; 92 (21)


    Reoviruses carry out genomic RNA transcription within intact viruses to synthesize plus-sense RNA strands, which are capped prior to their release as mRNA. The in situ structures of the transcriptional enzyme complex (TEC) containing the RNA-dependent RNA polymerase (RdRp) and NTPase are known for the single-layered reovirus cytoplasmic polyhedrosis virus (CPV), but not for multilayered reoviruses, such as aquareoviruses (ARV), which possess a primed stage that CPV lacks. Consequently, how the RNA genome and TEC respond to priming in reoviruses is unknown. Here, we determined the near-atomic-resolution asymmetric structure of ARV in the primed state by cryo-electron microscopy (cryo-EM), revealing the in situ structures of 11 TECs inside each capsid and their interactions with the 11 surrounding double-stranded RNA (dsRNA) genome segments and with the 120 enclosing capsid shell protein (CSP) VP3 subunits. The RdRp VP2 and the NTPase VP4 associate with each other and with capsid vertices; both bind RNA in multiple locations, including a novel C-terminal domain of VP4. Structural comparison between the primed and quiescent states showed translocation of the dsRNA end from the NTPase to the RdRp during priming. The RNA template channel was open in both states, suggesting that channel blocking is not a regulating mechanism between these states in ARV. Instead, the NTPase C-terminal domain appears to regulate RNA translocation between the quiescent and primed states. Taking the data together, dsRNA viruses appear to have adapted divergent mechanisms to regulate genome transcription while retaining similar mechanisms to coassemble their genome segments, TEC, and capsid proteins into infectious virions.IMPORTANCE Viruses in the family Reoviridae are characterized by the ability to endogenously synthesize nascent RNA within the virus. However, the mechanisms for assembling their RNA genomes with transcriptional enzymes into a multilayered virion and for priming such a virion for transcription are poorly understood. By cryo-EM and novel asymmetric reconstruction, we determined the atomic structure of the transcription complex inside aquareoviruses (ARV) that are primed for infection. The transcription complex is anchored by the N-terminal segments of enclosing capsid proteins and contains an NTPase and a polymerase. The NTPase has a newly discovered domain that translocates the 5' end of plus-sense RNA in segmented dsRNA genomes from the NTPase to polymerase VP2 when the virus changes from the inactive (quiescent) to the primed state. Conformation changes in capsid proteins and transcriptional complexes suggest a mechanism for relaying information from the outside to the inside of the virus during priming.

    View details for DOI 10.1128/JVI.00774-18

    View details for Web of Science ID 000447139100006

    View details for PubMedID 30068643

    View details for PubMedCentralID PMC6189512

  • Solution Structures of Engineered Vault Particles STRUCTURE Ding, K., Zhang, X., Mrazek, J., Kickhoefer, V. A., Lai, M., Ng, H. L., Yang, O. O., Rome, L. H., Zhou, Z. 2018; 26 (4): 619-+


    Prior crystal structures of the vault have provided clues of its structural variability but are non-conclusive due to crystal packing. Here, we obtained vaults by engineering at the N terminus of rat major vault protein (MVP) an HIV-1 Gag protein segment and determined their near-atomic resolution (∼4.8 Å) structures in a solution/non-crystalline environment. The barrel-shaped vaults in solution adopt two conformations, 1 and 2, both with D39 symmetry. From the N to C termini, each MVP monomer has three regions: body, shoulder, and cap. While conformation 1 is identical to one of the crystal structures, the shoulder in conformation 2 is translocated longitudinally up to 10 Å, resulting in an outward-projected cap. Our structures clarify the structural discrepancies in the body region in the prior crystallography models. The vault's drug-delivery potential is highlighted by the internal disposition and structural flexibility of its Gag-loaded N-terminal extension at the barrel waist of the engineered vault.

    View details for DOI 10.1016/j.str.2018.02.014

    View details for Web of Science ID 000429158900013

    View details for PubMedID 29551289

    View details for PubMedCentralID PMC5906032

  • Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)-Targeted Photothermal Therapy SLAS TECHNOLOGY Mayle, K. M., Dern, K. R., Wong, V. K., Chen, K. Y., Sung, S., Ding, K., Rodriguez, A. R., Knowles, S., Taylor, Z., Zhou, Z., Grundfest, W. S., Wu, A. M., Deming, T. J., Kamei, D. T. 2017; 22 (1): 26–35


    Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.

    View details for DOI 10.1177/2211068216669710

    View details for Web of Science ID 000393942600006

    View details for PubMedID 27659802

    View details for PubMedCentralID PMC6071911

  • Polypeptide-Based Gold Nanoshells for Photothermal Therapy SLAS TECHNOLOGY Mayle, K. M., Dern, K. R., Wong, V. K., Sung, S., Ding, K., Rodriguez, A. R., Taylor, Z., Zhou, Z., Grundfest, W. S., Deming, T. J., Kamei, D. T. 2017; 22 (1): 18–25


    Targeted killing of cancer cells by engineered nanoparticles holds great promise for noninvasive photothermal therapy applications. We present the design and generation of a novel class of gold nanoshells with cores composed of self-assembled block copolypeptide vesicles with photothermal properties. Specifically, poly(L-lysine)60- block-poly(L-leucine)20 (K60L20) block copolypeptide vesicles coated with a thin layer of gold demonstrate enhanced absorption of light due to surface plasmon resonance (SPR) in the near-infrared range. We show that the polypeptide-based K60L20 gold nanoshells have low toxicity in the absence of laser exposure, significant heat generation upon exposure to near-infrared light, and, as a result, localized cytotoxicity within the region of laser irradiation in vitro. To gain a better understanding of our gold nanoshells in the context of photothermal therapy, we developed a comprehensive mathematical model for heat transfer and experimentally validated this model by predicting the temperature as a function of time and position in our experimental setup. This model can be used to predict which parameters of our gold nanoshells can be manipulated to improve heat generation for tumor destruction. To our knowledge, our results represent the first ever use of block copolypeptide vesicles as the core material of gold nanoshells.

    View details for DOI 10.1177/2211068216645292

    View details for Web of Science ID 000393942600005

    View details for PubMedID 27126980

    View details for PubMedCentralID PMC6070380

  • Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes NATURE COMMUNICATIONS Zhang, X., Lai, M., Chang, W., Yu, I., Ding, K., Mrazek, J., Ng, H. L., Yang, O. O., Maslov, D. A., Zhou, Z. 2016; 7: 13223


    The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments. The structure also fashions many large rRNA expansion segments. Direct comparison of our human and leishmanial ribosome structures at the decoding A-site sheds light on how the bacterial ribosome-targeting drug paromomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome.

    View details for DOI 10.1038/ncomms13223

    View details for Web of Science ID 000385538700001

    View details for PubMedID 27752045

    View details for PubMedCentralID PMC5071889

  • In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus NATURE Zhang, X., Ding, K., Yu, X., Chang, W., Sun, J., Zhou, Z. 2015; 527 (7579): 531-+


    Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus.

    View details for DOI 10.1038/nature15767

    View details for Web of Science ID 000365352500051

    View details for PubMedID 26503045

    View details for PubMedCentralID PMC5086257