Honors & Awards
Rhodes Scholarship, Rhodes Trust (2012)
Education & Certifications
Masters of Science, University of Oxford, Radiation Biology (2013)
Bachelor of Science, Wake Forest University, Biophysics (2012)
2018 Spring - NENS 301A Neurology Core Clerkship
2018 Spring - RADO 300A Radiation Oncology Clerkship
2017 Spring - FAMMED 301A Family Medicine Core Clerkship
2017 Spring - MED 313A Ambulatory Medicine Core Clerkship
2016 Autumn - MED 300A Internal Medicine Core Clerkship
2016 Spring - SURG 300A Surgery Core Clerkship
2016 Summer - MED 300A Internal Medicine Core Clerkship
2016 Summer - PEDS 300A Pediatrics Core Clerkship
Chemical Space Mimicry for Drug Discovery
JOURNAL OF CHEMICAL INFORMATION AND MODELING
2017; 57 (4): 875-882
We describe a new library generation method, Machine-based Identification of Molecules Inside Characterized Space (MIMICS), that generates sets of molecules inspired by a text-based input. MIMICS-generated libraries were found to preserve distributions of properties while simultaneously increasing structural diversity. Newly identified MIMICS-generated compounds were found to be bioactive as inhibitors of specific components of the unfolded protein response (UPR) and the VEGFR2 pathway in cell-based assays, thus confirming the applicability of this methodology toward drug design applications. Wider application of MIMICS could facilitate the efficient utilization of chemical space.
View details for DOI 10.1021/acs.jcim.6b00754
View details for Web of Science ID 000400204900023
View details for PubMedID 28257191
An approach to functionally relevant clustering of the protein universe: Active site profile-based clustering of protein structures and sequences
2017; 26 (4): 677-699
Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification-amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two-Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure-Function Linkage Database, SFLD) self-identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self-identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well-curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP-identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F-measure and performance analysis on the enolase search results and comparison to GEMMA and SCI-PHY demonstrate that TuLIP avoids the over-division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results.
View details for DOI 10.1002/pro.3112
View details for Web of Science ID 000398183800005
View details for PubMedID 28054422
View details for PubMedCentralID PMC5368075
Comprehensive Analysis of the Unfolded Protein Response in Breast Cancer Subtypes.
JCO precision oncology
Purpose: Triple-negative breast cancers (TNBCs) are associated with a worse prognosis and patients with TNBC have fewer therapeutic options than patients with non-TNBC. Recently, the IRE1alpha-XBP1 branch of the unfolded protein response (UPR) was implicated in TNBC prognosis on the basis of a relatively small patient population, suggesting the diagnostic and therapeutic value of this pathway in TNBCs. In addition, the IRE1alpha-XBP1 and hypoxia-induced factor 1 alpha (HIF1alpha) pathways have been identified as interacting partners in TNBC, suggesting a novel mechanism of regulation. To comprehensively evaluate and validate these findings, we investigated the relative activities and relevance to patient survival of the UPR and HIF1alpha pathways in different breast cancer subtypes in large populations of patients.Materials and Methods: We performed a comprehensive analysis of gene expression and survival data from large cohorts of patients with breast cancer. The patients were stratified based on the average expression of the UPR or HIF1alpha gene signatures.Results: We identified a strong positive association between the XBP1 gene signature and estrogen receptor-positive status or the HIF1alpha gene signature, as well as the predictive value of the XBP1 gene signature for survival of patients who are estrogen receptor negative, or have TNBC or HER2+. In contrast, another important UPR branch, the ATF4/CHOP pathway, lacks prognostic value in breast cancer in general. Activity of the HIF1alpha pathway is correlated with patient survival in all the subtypes evaluated.Conclusion: These findings clarify the relevance of the UPR pathways in different breast cancer subtypes and underscore the potential therapeutic importance of the IRE1alpha-XBP1 branch in breast cancer treatment.
View details for DOI 10.1200/PO.16.00073
View details for PubMedID 29888341
Pulmonary Artery Pressure Response to Simulated Air Travel in a Hypobaric Chamber
AEROSPACE MEDICINE AND HUMAN PERFORMANCE
2015; 86 (6): 529-534
Hypoxia-induced elevation in pulmonary artery pressure during air travel may contribute to the worldwide burden of in-flight medical emergencies. The pulmonary artery pressure response may be greater in older passengers, who are more likely to require flight diversion due to a medical event. Understanding these effects may ultimately improve the safety of air travel.We studied 16 healthy volunteers, consisting of a younger group (aged <25 yr) and an older group (aged >60 yr). Using a hypobaric chamber, subjects undertook a 2-h simulated flight at the maximum cabin pressure altitude for commercial airline flights (8000 ft; 2438 m). Higher and lower altitudes within the aeromedical range were also explored. Systolic pulmonary artery pressure (sPAP) was assessed by Doppler echocardiography.There was a progressive increase in sPAP which appeared to be biphasic, with a small initial increase and a larger subsequent rise. Overall, sPAP increased by 5±1 mmHg from baseline to 35±1 mmHg at 8000 ft, an increase of 18%. The sPAP response to 8000 ft was greater in the older group than the younger group.This study confirms that pulmonary artery pressure increases during simulated air travel, and provides preliminary evidence that this response is greater in older people. Advancing age may increase in-flight susceptibility to adverse pulmonary vascular responses in passengers, aircrew, and aeromedical patients.
View details for DOI 10.3357/AMHP.4177.2015
View details for Web of Science ID 000357383700004
View details for PubMedID 26099124
Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans.
2014; 2 (12)
Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia-inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double-blind, crossover protocol which studied the effects of high-dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P < 0.001). In contrast, supraphysiological supplementation of ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF-mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.
View details for DOI 10.14814/phy2.12220
View details for PubMedID 25501423
View details for PubMedCentralID PMC4332205