Honors & Awards
Gates Millennium Scholarship, Bill & Melinda Gates Foundation / UNCF (2008)
Graduate Research Fellowship, National Science Foundation (NSF) (2012)
Gilliam Fellowships for Advanced Study, Howard Hughes Medical Institute (2015)
Professional Affiliations and Activities
Member, Stanford Human Subjects Institutional Review Board (2015 - Present)
President, Stanford Biosciences Student Association (2016 - 2017)
CGAP Graduate Student Representative, Stanford Biosciences Committee on Graduate Admissions and Policy (2014 - 2017)
Education & Certifications
B.S., Massachusetts Institute of Technology, Biology & Brain and Cognitive Sciences (2012)
Mark Schnitzer, Doctoral (Program)
Current Research and Scholarly Interests
Basic understanding of the mechanisms underlying autophagy, chaperones, and protein quality control in the nervous system as a route to more effective therapies for neurodegenerative diseases (Alzheimer's, Frontotemporal Dementia, Huntington's, etc.).
Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.
Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, L-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in L-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.
View details for DOI 10.1038/s41586-018-0090-6
View details for PubMedID 29720658
Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice
2017; 171 (5): 1176-+
The medial amygdala (MeA) plays a critical role in processing species- and sex-specific signals that trigger social and defensive behaviors. However, the principles by which this deep brain structure encodes social information is poorly understood. We used a miniature microscope to image the Ca2+ dynamics of large neural ensembles in awake behaving mice and tracked the responses of MeA neurons over several months. These recordings revealed spatially intermingled subsets of MeA neurons with distinct temporal dynamics. The encoding of social information in the MeA differed between males and females and relied on information from both individual cells and neuronal populations. By performing long-term Ca2+ imaging across different social contexts, we found that sexual experience triggers lasting and sex-specific changes in MeA activity, which, in males, involve signaling by oxytocin. These findings reveal basic principles underlying the brain's representation of social information and its modulation by intrinsic and extrinsic factors.
View details for DOI 10.1016/j.cell.2017.10.015
View details for Web of Science ID 000415317000019
View details for PubMedID 29107332
View details for PubMedCentralID PMC5731476
SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons
2013; 16 (8): 1008-U54
Defects in DNA repair have been linked to cognitive decline with age and neurodegenerative disease, yet the mechanisms that protect neurons from genotoxic stress remain largely obscure. We sought to characterize the roles of the NAD(+)-dependent deacetylase SIRT1 in the neuronal response to DNA double-strand breaks (DSBs). We found that SIRT1 was rapidly recruited to DSBs in postmitotic neurons, where it showed a synergistic relationship with ataxia telangiectasia mutated (ATM). SIRT1 recruitment to breaks was ATM dependent; however, SIRT1 also stimulated ATM autophosphorylation and activity and stabilized ATM at DSB sites. After DSB induction, SIRT1 also bound the neuroprotective class I histone deacetylase HDAC1. We found that SIRT1 deacetylated HDAC1 and stimulated its enzymatic activity, which was necessary for DSB repair through the nonhomologous end-joining pathway. HDAC1 mutations that mimic a constitutively acetylated state rendered neurons more susceptible to DNA damage, whereas pharmacological SIRT1 activators that promoted HDAC1 deacetylation also reduced DNA damage in two mouse models of neurodegeneration. We propose that SIRT1 is an apical transducer of the DSB response and that SIRT1 activation offers an important therapeutic avenue in neurodegeneration.
View details for DOI 10.1038/nn.3460
View details for Web of Science ID 000322323000010
View details for PubMedID 23852118
View details for PubMedCentralID PMC4758134
- On the Technology Prospects and Investment Opportunities for Scalable Neuroscience arXiv 2013; 1307 (7302)