Honors & Awards

  • Bowes Graduate Student Fellowship, Stanford Bio-X (2020-2023)

Education & Certifications

  • Bachelor of Arts, Princeton University, Molecular Biology (2014)
  • Doctor of Philosophy, Stanford University, BIO-PHD (2023)

All Publications

  • Embryonically Active Piriform Cortex Neurons Promote Intracortical Recurrent Connectivity during Development bioRxiv Wang, D. C., Santos Valencia, F. G., Song, J. H., Franks, K. M., Luo, L. 2024
  • Loss of Rai1 enhances hippocampal excitability and epileptogenesis in mouse models of Smith-Magenis syndrome. Proceedings of the National Academy of Sciences of the United States of America Chang, Y., Kowalczyk, M., Fogerson, P. M., Lee, Y., Haque, M., Adams, E. L., Wang, D. C., DeNardo, L. A., Tessier-Lavigne, M., Huguenard, J. R., Luo, L., Huang, W. 2022; 119 (43): e2210122119


    Hyperexcitability of brain circuits is a common feature of autism spectrum disorders (ASDs). Genetic deletion of a chromatin-binding protein, retinoic acid induced 1 (RAI1), causes Smith-Magenis syndrome (SMS). SMS is a syndromic ASD associated with intellectual disability, autistic features, maladaptive behaviors, overt seizures, and abnormal electroencephalogram (EEG) patterns. The molecular and neural mechanisms underlying abnormal brain activity in SMS remain unclear. Here we show that panneural Rai1 deletions in mice result in increased seizure susceptibility and prolonged hippocampal seizure duration invivo and increased dentate gyrus population spikes ex vivo. Brain-wide mapping of neuronal activity pinpointed selective cell types within the limbic system, including the hippocampal dentate gyrus granule cells (dGCs) that are hyperactivated by chemoconvulsant administration or sensory experience in Rai1-deficient brains. Deletion of Rai1 from glutamatergic neurons, but not from gamma-aminobutyric acidergic (GABAergic) neurons, was responsible for increased seizure susceptibility. Deleting Rai1 from the Emx1Cre-lineage glutamatergic neurons resulted in abnormal dGC properties, including increased excitatory synaptic transmission and increased intrinsic excitability. Our work uncovers the mechanism of neuronal hyperexcitability in SMS by identifying Rai1 as a negative regulator of dGC intrinsic and synaptic excitability.

    View details for DOI 10.1073/pnas.2210122119

    View details for PubMedID 36256819

  • Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals. Nature methods Su, Y., Walker, J. R., Park, Y., Smith, T. P., Liu, L. X., Hall, M. P., Labanieh, L., Hurst, R., Wang, D. C., Encell, L. P., Kim, N., Zhang, F., Kay, M. A., Casey, K. M., Majzner, R. G., Cochran, J. R., Mackall, C. L., Kirkland, T. A., Lin, M. Z. 2020


    Sensitive detection of two biological events in vivo has long been a goal in bioluminescence imaging. Antares, a fusion of the luciferase NanoLuc to the orange fluorescent protein CyOFP, has emerged as a bright bioluminescent reporter with orthogonal substrate specificity to firefly luciferase (FLuc) and its derivatives such as AkaLuc. However, the brightness of Antares in mice is limited by the poor solubility and bioavailability of the NanoLuc substrate furimazine. Here, we report a new substrate, hydrofurimazine, whose enhanced aqueous solubility allows delivery of higher doses to mice. In the liver, Antares with hydrofurimazine exhibited similar brightness to AkaLuc with its substrate AkaLumine. Further chemical exploration generated a second substrate, fluorofurimazine, with even higher brightness in vivo. We used Antares with fluorofurimazine to track tumor size and AkaLuc with AkaLumine to visualize CAR-T cells within the same mice, demonstrating the ability to perform two-population imaging with these two luciferase systems.

    View details for DOI 10.1038/s41592-020-0889-6

    View details for PubMedID 32661427

  • Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith-Magenis syndrome. Proceedings of the National Academy of Sciences of the United States of America Huang, W., Wang, D. C., Allen, W. E., Klope, M., Hu, H., Shamloo, M., Luo, L. 2018


    Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), a syndromic autism spectrum disorder associated with craniofacial abnormalities, intellectual disability, and behavioral problems. There is currently no cure for SMS. Here, we generated a genetic mouse model to determine the reversibility of SMS-like neurobehavioral phenotypes in Rai1 heterozygous mice. We show that normalizing the Rai1 level 3-4 wk after birth corrected the expression of genes related to neural developmental pathways and fully reversed a social interaction deficit caused by Rai1 haploinsufficiency. In contrast, Rai1 reactivation 7-8 wk after birth was not beneficial. We also demonstrated that the correct Rai1 dose is required in both excitatory and inhibitory neurons for proper social interactions. Finally, we found that Rai1 heterozygous mice exhibited a reduction of dendritic spines in the medial prefrontal cortex (mPFC) and that optogenetic activation of mPFC neurons in adults improved the social interaction deficit of Rai1 heterozygous mice. Together, these results suggest the existence of a postnatal temporal window during which restoring Rai1 can improve the transcriptional and social behavioral deficits in a mouse model of SMS. It is possible that circuit-level interventions would be beneficial beyond this critical window.

    View details for PubMedID 30275311

  • RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks MOLECULAR CELL Elia, A. H., Wang, D. C., Willis, N. A., Boardman, A. P., Hajdu, I., Adeyemi, R. O., Lowry, E., Gygi, S. P., Scully, R., Elledge, S. J. 2015; 60 (2): 280–93


    We have used quantitative proteomics to profile ubiquitination in the DNA damage response (DDR). We demonstrate that RPA, which functions as a protein scaffold in the replication stress response, is multiply ubiquitinated upon replication fork stalling. Ubiquitination of RPA occurs on chromatin, involves sites outside its DNA binding channel, does not cause proteasomal degradation, and increases under conditions of fork collapse, suggesting a role in repair at stalled forks. We demonstrate that the E3 ligase RFWD3 mediates RPA ubiquitination. RFWD3 is necessary for replication fork restart, normal repair kinetics during replication stress, and homologous recombination (HR) at stalled replication forks. Mutational analysis suggests that multisite ubiquitination of the entire RPA complex is responsible for repair at stalled forks. Multisite protein group sumoylation is known to promote HR in yeast. Our findings reveal a similar requirement for multisite protein group ubiquitination during HR at stalled forks in mammalian cells.

    View details for DOI 10.1016/j.molcel.2015.09.011

    View details for Web of Science ID 000366585400010

    View details for PubMedID 26474068

    View details for PubMedCentralID PMC4609029

  • Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response MOLECULAR CELL Elia, A. H., Boardman, A. P., Wang, D. C., Huttlin, E. L., Everley, R. A., Dephoure, N., Zhou, C., Koren, I., Gygi, S. P., Elledge, S. J. 2015; 59 (5): 867–81


    Execution of the DNA damage response (DDR) relies upon a dynamic array of protein modifications. Using quantitative proteomics, we have globally profiled ubiquitination, acetylation, and phosphorylation in response to UV and ionizing radiation. To improve acetylation site profiling, we developed the strategy FACET-IP. Our datasets of 33,500 ubiquitination and 16,740 acetylation sites provide valuable insight into DDR remodeling of the proteome. We find that K6- and K33-linked polyubiquitination undergo bulk increases in response to DNA damage, raising the possibility that these linkages are largely dedicated to DDR function. We also show that Cullin-RING ligases mediate 10% of DNA damage-induced ubiquitination events and that EXO1 is an SCF-Cyclin F substrate in the response to UV radiation. Our extensive datasets uncover additional regulated sites on known DDR players such as PCNA and identify previously unknown DDR targets such as CENPs, underscoring the broad impact of the DDR on cellular physiology.

    View details for DOI 10.1016/j.molcel.2015.05.006

    View details for Web of Science ID 000365166100016

    View details for PubMedID 26051181

    View details for PubMedCentralID PMC4560960