I am a fourth year medical student at Stanford. My current interests are otolaryngology/head and neck surgery, family medicine, or emergency medicine. Regardless of specialty, I am very interested in medical education and improving access to care.
The Summer Match: A qualitative study exploring a two-stage residency match option.
AEM education and training
2021; 5 (3): e10616
Background: The number of residency applications submitted by medical students rises annually, resulting in increased work and costs for residency programs and applicants, particularly in emergency medicine. We propose a solution to this problem: an optional, two-stage Match with a "summer match" stage, in which applicants can submit a limited number of applications early. This would be conducted similarly to the early decision process for college admissions. The study objectives were to explore stakeholder opinions on the feasibility of a summer match and to identify the ideal logistic parameters to operationalize this proposal.Methods: We used exploratory qualitative methodology following a constructivist paradigm to develop an understanding of the potential impact of a summer match. We interviewed 34 key stakeholders in the U.S. residency application process identified through purposive sampling including educational administrators (program directors, designated institutional officials, medical school deans) and trainees (students, residents). We coded and thematically analyzed interview data in two stages using an inductive approach.Results: We identified six themes from the participant interviews that broadly reflected issues of the residency application process, value, and equity. These themes included disrupting the status quo, logistic concerns, match strategy, differential benefits, unintended consequences, and return on investment. Most study participants supported the summer match concept, with medical students and residents most in favor. We developed a theoretical summer match protocol based on these findings.Conclusions: A summer match may reduce the burdens of increasing residency applications and associated costs. Pilot testing is necessary to confirm this hypothesis and determine the impact of the proposed summer match protocol. Unintended consequences must be considered carefully during implementation.
View details for DOI 10.1002/aet2.10616
View details for PubMedID 34222750
Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping.
2020; 21 (1): 135
To investigate the epigenetic and transcriptional mechanisms of coronary artery disease (CAD) risk, as well as the functional regulation of chromatin structure and function, we create a catalog of genetic variants associated with three stages of transcriptional cis-regulation in primary human coronary artery vascular smooth muscle cells (HCASMCs).We use a pooling approach with HCASMC lines to map regulatory variants that mediate binding of the CAD-associated transcription factor TCF21 with ChIPseq studies (bQTLs), variants that regulate chromatin accessibility with ATACseq studies (caQTLs), and chromosomal looping with Hi-C methods (clQTLs). We examine the overlap of these QTLs and their relationship to smooth muscle-specific genes and transcription factors. Further, we use multiple analyses to show that these QTLs are highly associated with CAD GWAS loci and correlate to lead SNPs where they show allelic effects. By utilizing genome editing, we verify that identified functional variants can regulate both chromatin accessibility and chromosomal looping, providing new insights into functional mechanisms regulating chromatin state and chromosomal structure. Finally, we directly link the disease-associated TGFB1-SMAD3 pathway to the CAD-associated FN1 gene through a response QTL that modulates both chromatin accessibility and chromosomal looping.Together, these studies represent the most thorough mapping of multiple QTL types in a highly disease-relevant primary cultured cell type and provide novel insights into their functional overlap and mechanisms that underlie these genomic features and their relationship to disease risk.
View details for DOI 10.1186/s13059-020-02049-5
View details for PubMedID 32513244
Fine-mapping cis-regulatory variants in diverse human populations.
Genome-wide association studies (GWAS) are a powerful approach for connecting genotype to phenotype. Most GWAS hits are located in cis-regulatory regions, but the underlying causal variants and their molecular mechanisms remain unknown. To better understand human cis-regulatory variation, we mapped quantitative trait loci for chromatin accessibility (caQTLs)-a key step in cis-regulation-in 1000 individuals from 10 diverse populations. Most caQTLs were shared across populations, allowing us to leverage the genetic diversity to fine-map candidate causal regulatory variants, several thousand of which have been previously implicated in GWAS. In addition, many caQTLs that affect the expression of distal genes also alter the landscape of long-range chromosomal interactions, suggesting a mechanism for long-range expression QTLs. In sum, our results show that molecular QTL mapping integrated across diverse populations provides a high-resolution view of how worldwide human genetic variation affects chromatin accessibility, gene expression, and phenotype.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor issues remain unresolved (see decision letter).
View details for PubMedID 30650056
Genomic Survey of Premetazoans Shows Deep Conservation of Cytoplasmic Tyrosine Kinases and Multiple Radiations of Receptor Tyrosine Kinases
2012; 5 (222): ra35
The evolution of multicellular metazoans from a unicellular ancestor is one of the most important advances in the history of life. Protein tyrosine kinases play important roles in cell-to-cell communication, cell adhesion, and differentiation in metazoans; thus, elucidating their origins and early evolution is crucial for understanding the origin of metazoans. Although tyrosine kinases exist in choanoflagellates, few data are available about their existence in other premetazoan lineages. To unravel the origin of tyrosine kinases, we performed a genomic and polymerase chain reaction (PCR)-based survey of the genes that encode tyrosine kinases in the two described filasterean species, Capsaspora owczarzaki and Ministeria vibrans, the closest relatives to the Metazoa and Choanoflagellata clades. We present 103 tyrosine kinase-encoding genes identified in the whole genome sequence of C. owczarzaki and 15 tyrosine kinase-encoding genes cloned by PCR from M. vibrans. Through detailed phylogenetic analysis, comparison of the organizations of the protein domains, and resequencing and revision of tyrosine kinase sequences previously found in some whole genome sequences, we demonstrate that the basic repertoire of metazoan cytoplasmic tyrosine kinases was established before the divergence of filastereans from the Metazoa and Choanoflagellata clades. In contrast, the receptor tyrosine kinases diversified extensively in each of the filasterean, choanoflagellate, and metazoan clades. This difference in the divergence patterns between cytoplasmic tyrosine kinases and receptor tyrosine kinases suggests that receptor tyrosine kinases that had been used for receiving environmental cues were subsequently recruited as a communication tool between cells at the onset of metazoan multicellularity.
View details for DOI 10.1126/scisignal.2002733
View details for Web of Science ID 000303542300002
View details for PubMedID 22550341
The Selaginella Genome Identifies Genetic Changes Associated with the Evolution of Vascular Plants
2011; 332 (6032): 960-963
Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
View details for DOI 10.1126/science.1203810
View details for Web of Science ID 000290766600042
View details for PubMedID 21551031
View details for PubMedCentralID PMC3166216
The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology
2011; 12 (7): R66
The major human intestinal pathogen Giardia lamblia is a very early branching eukaryote with a minimal genome of broad evolutionary and biological interest.To explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.The reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.
View details for PubMedID 21787419
The Amphimedon queenslandica genome and the evolution of animal complexity.
2010; 466 (7307): 720–26
Sponges are an ancient group of animals that diverged from other metazoans over 600 million years ago. Here we present the draft genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef, and show that it is remarkably similar to other animal genomes in content, structure and organization. Comparative analysis enabled by the sequencing of the sponge genome reveals genomic events linked to the origin and early evolution of animals, including the appearance, expansion and diversification of pan-metazoan transcription factor, signalling pathway and structural genes. This diverse 'toolkit' of genes correlates with critical aspects of all metazoan body plans, and comprises cell cycle control and growth, development, somatic- and germ-cell specification, cell adhesion, innate immunity and allorecognition. Notably, many of the genes associated with the emergence of animals are also implicated in cancer, which arises from defects in basic processes associated with metazoan multicellularity.
View details for DOI 10.1038/nature09201
View details for PubMedID 20686567
View details for PubMedCentralID PMC3130542