Extensive experience in statistical modelling, inference, and multiple hypothesis testing by analyzing various types of data, including genomic and gene expression data.
Current Role at Stanford
Primarily collaborating with VA researchers on GWAS using MVP data. Also providing statistical support to some Stanford clinicians conducting investigational research.
Education & Certifications
MS, Stanford University, Statistics (2014)
MS & PhD, Cornell University, Applied Mathematics (1993)
BS, New Mexico Institute of Mining & Technology, Mathematics (1985)
Corneal Light Scatter After Ultrathin Descemet Stripping Automated Endothelial Keratoplasty Versus Descemet Membrane Endothelial Keratoplasty in Descemet Endothelial Thickness Comparison Trial: A Randomized Controlled Trial.
PURPOSE: To compare the degree of corneal light scatter as measured by densitometry in ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK) in the Descemet endothelial thickness comparison trial.METHODS: This was a prespecified secondary analysis of the Descemet endothelial thickness comparison trial, which was a prospective, randomized controlled trial. Subjects with isolated endothelial dysfunction were enrolled and were randomized to either UT-DSAEK or DMEK. Corneal opacity was quantitatively measured by Pentacam densitometry (OCULUS) at 3, 6, and 12 months.RESULTS: Fifty eyes of 38 patients were enrolled at the Casey Eye Institute at Oregon Health & Science University and the Byers Eye Institute at Stanford University. Corneal densitometry for the anterior and posterior layers improved in both UT-DSAEK and DMEK after surgery. The decrease was more pronounced in the posterior layer for both groups. However, there was no difference in the degree of corneal light scatter between UT-DSAEK and DMEK at postoperative month 12, and no difference in change in densitometry was observed between the 2 arms from baseline to month 12.CONCLUSIONS: Both UT-DSAEK and DMEK experience an improvement in the degree of corneal light scatter after surgery. However, there was no difference in densitometry between the 2 groups at month 12. Therefore, other factors such as higher order aberrations in the posterior cornea rather than stromal-stromal interface haze mediate the superior visual outcomes in DMEK compared with UT-DSAEK.
View details for DOI 10.1097/ICO.0000000000002256
View details for PubMedID 31939923
Vision loss in optic disc drusen correlates with increased macular vessel diameter and flux and reduced peripapillary vascular density.
American journal of ophthalmology
To determine the key optical coherence tomography (OCT) and OCT angiography (OCTA) parameters that correlate with visual field loss in optic disc drusen (ODD).Retrospective cross-sectional study..Single academic center.17 patients with ODD (29 eyes) and 35 age-matched controls (53 eyes) INTERVENTION OR OBSERVATION PROCEDURES: Static perimetry, OCT and OCTA imaging of optic disc and macula.static perimetry, OCT, and OCTA measurements.We investigated the relationship between static perimetry and 14 OCT/OCTA measurements in patients with ODD vs. age-matched controls and found 5 key measurements that most correlated with visual field loss included: peripapillary retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC), peripapillary vessel area density (VAD), macular vessel diameter (VD) and flux. Hierarchical clustering of these 5 measurements vs. all clinical characteristics revealed 3 distinct clusters. ODD and control eyes with no visual field loss (mean deviation (MD) > -2.0 dB) had high RNFL, GCC, and low macular VD and flux. ODD eyes with mild visual field loss (MD -2.0 to -5.0 dB) had high RNFL, GCC, and increased macular VD and flux. ODD eyes with moderate/severe visual field loss (MD < -5.0 dB) had decreased RNFL, GCC, peripapillary VAD, and increased macular VD and flux.OCT and OCTA provided objective measurements that can help predict visual field loss in ODD. Our data suggest that increased macular flow may be an early biomarker of visual field loss in ODD, while decreased peripapillary vessel density and RNFL thickness are late biomarkers of visual field loss in ODD.
View details for DOI 10.1016/j.ajo.2020.04.019
View details for PubMedID 32360344
Exome sequencing of Finnish isolates enhances rare-variant association power.
Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exomesequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power.
View details for DOI 10.1038/s41586-019-1457-z
View details for PubMedID 31367044
Multiregion Quantification of Extracellular Signal-regulated Kinase Activity in Renal Cell Carcinoma.
European urology oncology
To personalize treatment for renal cell carcinoma (RCC), it would be ideal to confirm the activity of druggable protein pathways within individual tumors. We have developed a high-resolution nanoimmunoassay (NIA) to measure protein activity with high precision in scant specimens (eg, fine needle aspirates [FNAs]). Here, we used NIA to determine whether protein activation varied in different regions of RCC tumors. Since most RCC therapies target angiogenesis by inhibiting the vascular endothelial growth factor (VEGF) receptor, we quantified phosphorylation of extracellular signal-regulated kinase (ERK), a downstream effector of the VEGF signaling pathway. In 90 ex vivo FNA biopsies sampled from multiple regions of 38 primary clear cell RCC tumors, ERK phosphorylation differed among patients. In contrast, within individual patients, we found limited intratumoral heterogeneity of ERK phosphorylation. Our results suggest that measuring ERK in a single FNA may be representative of ERK activity in different regions of the same tumor. As diagnostic and therapeutic protein biomarkers are being sought, NIA measurements of protein signaling may increase the clinical utility of renal mass biopsy and allow for the application of precision oncology for patients with localized and advanced RCC. PATIENT SUMMARY: In this report, we applied a new approach to measure the activity of extracellular signal-regulated kinase (ERK), a key cancer signaling protein, in different areas within kidney cancers. We found that ERK activity varied between patients, but that different regions within individual kidney tumors showed similar ERK activity. This suggests that a single biopsy of renal cell carcinoma may be sufficient to measure protein signaling activity to aid in precision oncology approaches.
View details for DOI 10.1016/j.euo.2018.09.011
View details for PubMedID 31412000
Exposure to NO2, CO, and PM2.5 is linked to regional DNA methylation differences in asthma
2018; 10: 2
DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation (Foxp3 and IL10) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained (n = 188), and in a subset of subjects (n = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures.Asthma was significantly associated with higher differentially methylated regions (DMRs) of the Foxp3 promoter region (p = 0.030) and the IL10 intronic region (p = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), Foxp3 methylation was positively associated with NO2, CO, and PM2.5 exposures (p = 0.001, p = 0.001, and p = 0.012, respectively). In the subset of subjects retested 2 years later (n = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average Foxp3 methylation of the promoter region and activated Treg levels (p = 0.039) and a positive correlation between the average IL10 methylation of region 3 of intron 4 and IL10 cytokine expression (p = 0.030).Short-term and long-term exposures to high levels of CO, NO2, and PM2.5 were associated with alterations in differentially methylated regions of Foxp3. IL10 methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of Foxp3 and IL10.
View details for PubMedID 29317916
Genetic Variant Selection: Learning Across Traits and Sites
2016; 202 (2): 439-?
We consider resequencing studies of associated loci and the problem of prioritizing sequence variants for functional follow-up. Working within the multivariate linear regression framework helps us to account for the joint effects of multiple genes; and adopting a Bayesian approach leads to posterior probabilities that coherently incorporate all information about the variants' function. We describe two novel prior distributions that facilitate learning the role of each variable site by borrowing evidence across phenotypes and across mutations in the same gene. We illustrate their potential advantages with simulations and reanalyzing a data set of sequencing variants.
View details for DOI 10.1534/genetics.115.184572
View details for Web of Science ID 000371304600010
View details for PubMedID 26680660
View details for PubMedCentralID PMC4788227