I come from the beautiful view also known as Chula Vista, California. I graduated from the University of California Berkeley with a B.S. in Chemistry and a minor in Biological Engineering in 2019. At Berkeley, I worked under the guidance of Dr. Gabor Somorjai working in the field of surface science. I also spent time researching in the Vision Science Program studying lipid circuits and immune response with Dr. Karsten Gronert. While at UC Berkeley, I completed a summer internship at Genentech. In the Bogyo lab, I am interested in developing covalent cyclic peptide inhibitors for future use as therapeutics, imaging agents, and biological tools.
Honors & Awards
Cancer Early Detection Graduate Fellowship, Alliance for Cancer Early Detection, Canary Center (2022)
NIH Biotechnology Graduate Fellowship, NIH Stanford Biotechnology Training Program (2021)
Chemical Biology Interface Fellowship, Stanford CheM-H (2019)
Enhancing Diversity in Graduate Education Fellowship, Stanford (2019)
NSF Graduate Research Fellowship, National Science Foundation (2019)
Education & Certifications
Bachelors of Science, UC Berkeley, Chemistry, with Minor in Biological Engineering (2019)
Current Research and Scholarly Interests
Peptide Therapeutics and Diagnostics
Image Guided Surgery
Covalent Macrocyclic Proteasome Inhibitors Mitigate Resistance in Plasmodium falciparum.
ACS infectious diseases
The Plasmodium proteasome is a promising antimalarial drug target due to its essential role in all parasite lifecycle stages. Furthermore, proteasome inhibitors have synergistic effects when combined with current first-line artemisinin and related analogues. Linear peptides that covalently inhibit the proteasome are effective at killing parasites and have a low propensity for inducing resistance. However, these scaffolds generally suffer from poor pharmacokinetics and bioavailability. Here we describe the development of covalent, irreversible, macrocyclic inhibitors of the Plasmodium falciparum proteasome. We identified compounds with excellent potency and low cytotoxicity; however, the first generation suffered from poor microsomal stability. Further optimization of an existing macrocyclic scaffold resulted in an irreversible covalent inhibitor carrying a vinyl sulfone electrophile that retained high potency and low cytotoxicity and had acceptable metabolic stability. Importantly, unlike the parent reversible inhibitor that selected for multiple mutations in the proteasome, with one resulting in a 5,000-fold loss of potency, the irreversible analogue only showed a 5-fold loss in potency for any single point mutation. Furthermore, an epoxyketone analogue of the same scaffold retained potency against a panel of known proteasome mutants. These results confirm that macrocycles are optimal scaffolds to target the malarial proteasome and that the use of a covalent electrophile can greatly reduce the ability of the parasite to generate drug resistance mutations.
View details for DOI 10.1021/acsinfecdis.3c00310
View details for PubMedID 37712594
Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.
Nature chemical biology
Serine hydrolases have important roles in signaling and human metabolism, yet little is known about their functions in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Our functional studies reveal that BT4193 is a true homolog of hDPP4 that can be inhibited by FDA-approved type 2 diabetes medications targeting hDPP4, while the other is a misannotated proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and that loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. However, neither function is dependent on BT4193 proteolytic activity, suggesting a scaffolding or signaling function for this bacterial protease.
View details for DOI 10.1038/s41589-023-01357-8
View details for PubMedID 37349583
View details for PubMedCentralID 6108420
Protease Activated Probes for Real-Time Ratiometric Imaging of Solid Tumors
ACS CENTRAL SCIENCE
Surgery is the preferred treatment option for most solid tumors. However, inaccurate detection of cancer borders leads to either incomplete removal of malignant cells or excess excision of healthy tissue. While fluorescent contrast agents and imaging systems improve tumor visualization, they can suffer from low signal-to-background and are prone to technical artifacts. Ratiometric imaging has the potential to eliminate many of these issues such as uneven probe distribution, tissue autofluorescence, and changes in positioning of the light source. Here, we describe a strategy to convert quenched fluorescent probes into ratiometric contrast agents. Conversion of the cathepsin-activated probe, 6QC-Cy5, into a two-fluorophore probe, 6QC-RATIO, significantly improved signal-to-background in vitro and in a mouse subcutaneous breast tumor model. Tumor detection sensitivity was further enhanced using a dual-substrate AND-gate ratiometric probe, Death-Cat-RATIO, that fluoresces only after orthogonal processing by multiple tumor-specific proteases. We also designed and built a modular camera system that was coupled to the FDA-approved da Vinci Xi robot, to enable real-time imaging of ratiometric signals at video frame rates compatible with surgical workflows. Our results demonstrate that ratiometric camera systems and imaging probes have the potential to be clinically implemented to improve surgical resection of many types of cancer.
View details for DOI 10.1021/acscentsci.3c00261
View details for Web of Science ID 000985613600001
View details for PubMedID 37252358
View details for PubMedCentralID PMC10214504
Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows
Israel Journal of Chemistry
View details for DOI 10.1002/ijch.202300020
Strategies for Tuning the Selectivity of Chemical Probes that Target Serine Hydrolases.
Cell chemical biology
Serine hydrolases comprise a large family of enzymes that have diverse roles in key cellular processes, such as lipid metabolism, cell signaling, and regulation of post-translation modifications of proteins. They are also therapeutic targets for multiple human pathologies, including viral infection, diabetes, hypertension, and Alzheimer disease; however, few have well-defined substrates and biological functions. Activity-based probes (ABPs) have been used as effective tools to both profile activity and screen for selective inhibitors of serine hydrolases. One broad-spectrum ABP containing a fluorophosphonate electrophile has been used extensively to advance our understanding of diverse serine hydrolases. Due to the success of this single reagent, several robust chemistries have been developed to further diversify and tune the selectivity of ABPs used to target serine hydrolases. In this review, we highlight approaches to identify selective serine hydrolase ABPs and suggest new synthetic methodologies that could be applied to further advance probe development.
View details for DOI 10.1016/j.chembiol.2020.07.008
View details for PubMedID 32726586
- Supported iron catalysts for Michael addition reactions MOLECULAR CATALYSIS 2018; 447: 65-71
New Insights into Aldol Reactions of Methyl Isocyanoacetate Catalyzed by Heterogenized Homogeneous Catalysts
2017; 17 (1): 584-589
The Hayashi-Ito aldol reaction of methyl isocyanoacetate (MI) and benzaldehydes, a classic homogeneous Au(I)-catalyzed reaction, was studied with heterogenized homogeneous catalysts. Among dendrimer encapsulated nanoparticles (NPs) of Au, Pd, Rh, or Pt loaded in mesoporous supports and the homogeneous analogues, the Au NPs led to the highest yield and highest diastereoselectivity of products in toluene at room temperature. The Au catalyst was stable and was recycled for at least six runs without substantial deactivation. Moreover, larger pore sizes of the support and the use of a hydrophobic solvent led to a high selectivity for the trans diastereomer of the product. The activation energy is sensitive to neither the size of Au NPs nor the support. A linear Hammett plot was obtained with a positive slope, suggesting an increased electron density on the carbonyl carbon atom in the rate-limiting step. IR studies revealed a strong interaction between MI and the gold catalyst, supporting the proposed mechanism, in which rate-limiting step involves an electrophilic attack of the aldehyde on the enolate formed from the deprotonated MI.
View details for DOI 10.1021/acs.nanolett.6b04827
View details for Web of Science ID 000392036600082
View details for PubMedID 27966991