Assistant Professor, Psychiatry and Behavioral Sciences
Member, Wu Tsai Neurosciences Institute
Honors & Awards
NIH Autism Centers of Excellence grant, NICHD (2017-2022)
Siebel Fellowship, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University (2016)
California Institute for Regenerative Medicine Pre-Doctoral Fellowship, University of California, Berkeley (2008)
Helen Wills Neuroscience Institute Fellowship, University of California, Berkeley (2005)
Post-doctoral fellow, Harvard University, Stem Cell and Regenerative Biology (2015)
Ph.D., University of California, Berkeley, Neuroscience (2009)
B.A., University of California, Berkeley, Molecular and Cell Biology (2005)
A transient DMSO treatment increases the differentiation potential of human pluripotent stem cells through the Rb family
View details for DOI 10.1371/journal.pone.0208110
A qPCRCR ScoreCard quantifies the differentiation potential of human pluripotent stem cells
2015; 33 (11): 1182-U117
Research on human pluripotent stem cells has been hampered by the lack of a standardized, quantitative, scalable assay of pluripotency. We previously described an assay called ScoreCard that used gene expression signatures to quantify differentiation efficiency. Here we report an improved version of the assay based on qPCR that enables faster, more quantitative assessment of functional pluripotency. We provide an in-depth characterization of the revised signature panel (commercially available as the TaqMan hPSC Scorecard Assay) through embryoid body and directed differentiation experiments as well as a detailed comparison to the teratoma assay. We further show that the improved ScoreCard enables a wider range of applications, such as screening of small molecules, genetic perturbations and assessment of culture conditions. Our approach can be extended beyond stem cell applications to characterize and assess the utility of other cell types and lineages.
View details for DOI 10.1038/nbt.3387
View details for Web of Science ID 000364916000026
View details for PubMedID 26501952
A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation
JOURNAL OF CELL BIOLOGY
2015; 210 (7): 1257-1268
Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation.
View details for DOI 10.1083/jcb.201502035
View details for Web of Science ID 000362624000019
View details for PubMedID 26416968
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
2014; 19 (12): 1275-1283
Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.
View details for DOI 10.1038/mp.2013.190
View details for Web of Science ID 000345423500005
View details for PubMedID 24514565
A simple tool to improve pluripotent stem cell differentiation
2013; 10 (6): 553-?
We describe a method to help overcome restrictions on the differentiation propensities of human pluripotent stem cells. Culturing pluripotent stem cells in dimethylsulfoxide (DMSO) activates the retinoblastoma protein, increases the proportion of cells in the early G1 phase of the cell cycle and, in more than 25 embryonic and induced pluripotent stem cell lines, improves directed differentiation into multiple lineages. DMSO treatment also improves differentiation into terminal cell types in several cell lines.
View details for DOI 10.1038/NMETH.2442
View details for Web of Science ID 000319668700026
View details for PubMedID 23584186
Altered prefrontal function with aging: Insights into age-associated performance decline
2008; 1232: 30-47
We examined the effects of aging on visuo-spatial attention. Participants performed a bi-field visual selective attention task consisting of infrequent target and task-irrelevant novel stimuli randomly embedded among repeated standards in either attended or unattended visual fields. Blood oxygenation level dependent (BOLD) responses to the different classes of stimuli were measured using functional magnetic resonance imaging. The older group had slower reaction times to targets, and committed more false alarms but had comparable detection accuracy to young controls. Attended target and novel stimuli activated comparable widely distributed attention networks, including anterior and posterior association cortex, in both groups. The older group had reduced spatial extent of activation in several regions, including prefrontal, basal ganglia, and visual processing areas. In particular, the anterior cingulate and superior frontal gyrus showed more restricted activation in older compared with young adults across all attentional conditions and stimulus categories. The spatial extent of activations correlated with task performance in both age groups, but the regional pattern of association between hemodynamic responses and behavior differed between the groups. Whereas the young subjects relied on posterior regions, the older subjects engaged frontal areas. The results indicate that aging alters the functioning of neural networks subserving visual attention, and that these changes are related to cognitive performance.
View details for DOI 10.1016/j.brainres.2008.07.060
View details for Web of Science ID 000260196900004
View details for PubMedID 18691562
C-11-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration
2007; 68 (15): 1205-1212
The PET tracer (11)C-labeled Pittsburgh Compound-B ((11)C-PIB) specifically binds fibrillar amyloid-beta (Abeta) plaques and can be detected in Alzheimer disease (AD). We hypothesized that PET imaging with (11)C-PIB would discriminate AD from frontotemporal lobar degeneration (FTLD), a non-Abeta dementia.Patients meeting research criteria for AD (n = 7) or FTLD (n = 12) and cognitively normal controls (n = 8) underwent PET imaging with (11)C-PIB (patients and controls) and (18)F-fluorodeoxyglucose ((18)F-FDG) (patients only). (11)C-PIB whole brain and region of interest (ROI) distribution volume ratios (DVR) were calculated using Logan graphical analysis with cerebellum as a reference region. DVR images were visually rated by a blinded investigator as positive or negative for cortical (11)C-PIB, and summed (18)F-FDG images were rated as consistent with AD or FTLD.All patients with AD (7/7) had positive (11)C-PIB scans by visual inspection, while 8/12 patients with FTLD and 7/8 controls had negative scans. Of the four PIB-positive patients with FTLD, two had (18)F-FDG scans that suggested AD, and two had (18)F-FDG scans suggestive of FTLD. Mean DVRs were higher in AD than in FTLD in whole brain, lateral frontal, precuneus, and lateral temporal cortex (p < 0.05), while DVRs in FTLD did not significantly differ from controls.PET imaging with (11)C-labeled Pittsburgh Compound-B ((11)C-PIB) helps discriminate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD). Pathologic correlation is needed to determine whether patients with PIB-positive FTLD represent false positives, comorbid FTLD/AD pathology, or AD pathology mimicking an FTLD clinical syndrome.
View details for Web of Science ID 000245570100008
View details for PubMedID 17420404