San Francisco, California, United States
Contact Info
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About
Experience & Education
Volunteer Experience
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Science Communicator
Skype A Scientist
- Present 4 years 7 months
Education
Visiting K-12 classrooms around the world virtually to introduce students to a scientist and to facilitate a conversation on science as a discipline and a career.
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Health Professions Recruitment & Exposure Program
Harvard Medical School
- 4 years
Education
Mentored high school students from the Boston area, particularly those from underrepresented backgrounds, with the aim of recruiting them into science and medicine through the Health Professions Recruitment & Exposure Program (HPREP) at Harvard Medical School.
Served as an Executive Director for the 2021-22 program. Served as a Pod Leader to facilitate the mentoring sessions of nine mentor-mentee pairs 2019-2021 and as a Mentoring Director to coordinate and oversee the HPREP mentoring…Mentored high school students from the Boston area, particularly those from underrepresented backgrounds, with the aim of recruiting them into science and medicine through the Health Professions Recruitment & Exposure Program (HPREP) at Harvard Medical School.
Served as an Executive Director for the 2021-22 program. Served as a Pod Leader to facilitate the mentoring sessions of nine mentor-mentee pairs 2019-2021 and as a Mentoring Director to coordinate and oversee the HPREP mentoring component 2020-2021. -
Peer Reviewer
Journal of Emerging Investigators, Inc
- 3 years 6 months
Education
Served as a peer-reviewer for manuscripts submitted to the Journal of Emerging Investigators, a science journal and mentorship program that publishes research conducted by middle and high school scientists.
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K-8 Mentor, NE STEM 4U
University of Nebraska at Omaha
- 3 years 1 month
Education
Engaged 15 elementary/middle school students per session in underprivileged Omaha Public School districts with weekly interactive experiments in science, technology, engineering, and mathematics through Nebraska STEM 4U (NE STEM 4U) in the University of Nebraska at Omaha Department of Biology.
Schools included:
Kennedy Elementary, Miller Park Elementary, Norris Middle, King Science/Tech Magnet Middle
Transitioned to paid mentorship from Jan 2016 - May 2018. Served as Curriculum…Engaged 15 elementary/middle school students per session in underprivileged Omaha Public School districts with weekly interactive experiments in science, technology, engineering, and mathematics through Nebraska STEM 4U (NE STEM 4U) in the University of Nebraska at Omaha Department of Biology.
Schools included:
Kennedy Elementary, Miller Park Elementary, Norris Middle, King Science/Tech Magnet Middle
Transitioned to paid mentorship from Jan 2016 - May 2018. Served as Curriculum Director from 2017 - 2018. -
Reading Buddy, Harrison Elementary School
Omaha Public Schools
- 10 months
Education
Mentored and read with a small group of two immigrant/refugee-population elementary children to improve their reading skills and confidence.
Publications
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Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy
Nature Communications
Proteolysis-targeting chimeras (PROTACs) represent a new therapeutic modality involving selectively directing disease-causing proteins for degradation through proteolytic systems. Our ability to exploit targeted protein degradation (TPD) for antibiotic development remains nascent due to our limited understanding of which bacterial proteins are amenable to a TPD strategy. Here, we use a genetic system to model chemically-induced proximity and degradation to screen essential proteins in…
Proteolysis-targeting chimeras (PROTACs) represent a new therapeutic modality involving selectively directing disease-causing proteins for degradation through proteolytic systems. Our ability to exploit targeted protein degradation (TPD) for antibiotic development remains nascent due to our limited understanding of which bacterial proteins are amenable to a TPD strategy. Here, we use a genetic system to model chemically-induced proximity and degradation to screen essential proteins in Mycobacterium smegmatis (Msm), a model for the human pathogen M. tuberculosis (Mtb). By integrating experimental screening of 72 protein candidates and machine learning, we find that drug-induced proximity to the bacterial ClpC1P1P2 proteolytic complex leads to the degradation of many endogenous proteins, especially those with disordered termini. Additionally, TPD of essential Msm proteins inhibits bacterial growth and potentiates the effects of existing antimicrobial compounds. Together, our results provide biological principles to select and evaluate attractive targets for future Mtb PROTAC development, as both standalone antibiotics and potentiators of existing antibiotic efficacy.
Authors: Harim I. Won, Samuel Zinga, Olga Kandror, Tatos Akopian, Ian D. Wolf, Jessica T. P. Schweber, Ernst W. Schmid, Michael C. Chao, Maya Waldor, Eric J. Rubin & Junhao Zhu -
Spatiotemporal localization of proteins in mycobacteria
Cell Reports
Although prokaryotic organisms lack traditional organelles, they must still organize cellular structures in space and time, challenges that different species solve differently. To systematically define the subcellular architecture of mycobacteria, we perform high-throughput imaging of a library of fluorescently tagged proteins expressed in Mycobacterium smegmatis and develop a customized computational pipeline, MOMIA and GEMATRIA, to analyze these data. Our results establish a spatial…
Although prokaryotic organisms lack traditional organelles, they must still organize cellular structures in space and time, challenges that different species solve differently. To systematically define the subcellular architecture of mycobacteria, we perform high-throughput imaging of a library of fluorescently tagged proteins expressed in Mycobacterium smegmatis and develop a customized computational pipeline, MOMIA and GEMATRIA, to analyze these data. Our results establish a spatial organization network of over 700 conserved mycobacterial proteins and reveal a coherent localization pattern for many proteins of known function, including those in translation, energy metabolism, cell growth and division, as well as proteins of unknown function. Furthermore, our pipeline exploits morphologic proxies to enable a pseudo-temporal approximation of protein localization and identifies previously uncharacterized cell-cycle-dependent dynamics of essential mycobacterial proteins. Collectively, these data provide a systems perspective on the subcellular organization of mycobacteria and provide tools for the analysis of bacteria with non-standard growth characteristics.
Authors: Junhao Zhu, Ian D. Wolf, Charles L. Dulberger, Harim I. Won, Jemila C. Kester, Julius A. Judd, Samantha E. Wirth, Ryan R. Clark, Yawei Li, Yuan Luo, Todd A. Gray, Joseph T. Wade, Keith M. Derbyshire, Sarah M. Fortune, Eric J. RubinOther authorsSee publication -
Inactivation of the Pta-AckA pathway impairs fitness of Bacillus anthracis during overflow metabolism
Journal of Bacteriology
Under conditions of glucose excess, aerobically growing bacteria predominantly direct carbon flux towards acetate fermentation, a phenomenon known as overflow metabolism or the bacterial ‘Crabtree effect’. Numerous studies of the major acetate-generating pathway, the Pta-AckA, revealed its important role in bacterial fitness through the control of central metabolism to sustain balanced growth and cellular homeostasis. In this work, we highlight the contribution of the Pta-AckA pathway to…
Under conditions of glucose excess, aerobically growing bacteria predominantly direct carbon flux towards acetate fermentation, a phenomenon known as overflow metabolism or the bacterial ‘Crabtree effect’. Numerous studies of the major acetate-generating pathway, the Pta-AckA, revealed its important role in bacterial fitness through the control of central metabolism to sustain balanced growth and cellular homeostasis. In this work, we highlight the contribution of the Pta-AckA pathway to fitness of the spore-forming bacterium, Bacillus anthracis. We demonstrate that disruption of the Pta-AckA pathway causes a drastic growth reduction in the mutants and alters the metabolic and energy status of the cells. Our results revealed that inactivation of the Pta-AckA pathway increases the glucose consumption rate, affects intracellular ATP, NAD+ and NADH levels and leads to a metabolic block at the pyruvate and acetyl-CoA nodes. Consequently, accumulation of intracellular acetyl-CoA and pyruvate forces bacteria to direct carbon into the TCA and/or glyoxylate cycles as well as fatty acid and poly(3‐hydroxybutyrate) (PHB) biosynthesis pathways. Notably, the presence of phosphate butyryltransferase in B. anthracis partially compensates for the loss of phosphotransacetylase activity. Furthermore, overexpression of the ptb gene not only eliminates the negative impact of the pta mutation on B. anthracis fitness, but also restores normal growth in the pta mutant of the non-butyrate-producing bacterium, Staphylococcus aureus. Taken together, the results of this study demonstrate the importance of the Pta-AckA pathway for B. anthracis fitness by revealing its critical contribution to the maintenance of metabolic homeostasis during aerobic growth under conditions of carbon overflow.
Other authorsSee publication -
In vitro selection implicates ROP1 as a resistance gene for an experimental therapeutic benzoquinone acyl hydrazone in Toxoplasma gondii
Antimicrobial Agents and Chemotherapy
Toxoplasma gondii is a globally distributed apicomplexan parasite and the causative agent of toxoplasmosis in humans. While pharmaceuticals exist to combat acute infection, they can produce serious adverse reactions, demonstrating a need for enhanced therapies. KG8 is a benzoquinone acyl hydrazone chemotype identified from a previous chemical screen for which we previously showed in vitro and in vivo efficacy against T. gondii. However, the genetic target and mechanism of action of KG8 remain…
Toxoplasma gondii is a globally distributed apicomplexan parasite and the causative agent of toxoplasmosis in humans. While pharmaceuticals exist to combat acute infection, they can produce serious adverse reactions, demonstrating a need for enhanced therapies. KG8 is a benzoquinone acyl hydrazone chemotype identified from a previous chemical screen for which we previously showed in vitro and in vivo efficacy against T. gondii. However, the genetic target and mechanism of action of KG8 remain unknown. To investigate potential targets, we generated resistant T. gondii lines by chemical mutagenesis followed by in vitro selection. Whole-genome sequencing of resistant clones revealed a P207S mutation in the gene encoding rhoptry organelle protein 1 (ROP1) in addition to two lesser resistance-conferring mutations in the genes for rhoptry organelle protein 8 (ROP8) and a putative ADP/ATP carrier protein (TGGT1_237700). Expressing ROP1P207S in parental parasites was sufficient to confer significant (10.3-fold increased half-maximal effective concentration [EC50]) KG8 resistance. After generating a library of mutants carrying hypermutated rop1 alleles followed by KG8 pressure, we sequenced the most resistant clonal isolate (>16.9-fold increased EC50) and found independent recapitulation of the P207S mutation, along with three additional mutations in the same region. We also demonstrate that a rop1 knockout strain is insensitive to KG8. These data implicate ROP1 as a putative resistance gene of KG8. This work further identifies a compound that can be used in future studies to better understand ROP1 function and highlights this novel chemotype as a potential scaffold for the development of improved T. gondii therapeutics.
Other authorsSee publication -
De novo Assembly of the Burying Beetle Nicrophorus orbicollis (Coleoptera: Silphidae) Transcriptome Across Developmental Stages with Identification of Key Immune Transcripts
Journal of Genomics
Burying beetles (Nicrophorus spp.) are among the relatively few insects that provide parental care while not belonging to the eusocial insects such as ants or bees. This behavior incurs energy costs as evidenced by immune deficits and shorter life-spans in reproducing beetles. In the absence of an assembled transcriptome, relatively little is known concerning the molecular biology of these beetles. This work details the assembly and analysis of the Nicrophorus orbicollis transcriptome at…
Burying beetles (Nicrophorus spp.) are among the relatively few insects that provide parental care while not belonging to the eusocial insects such as ants or bees. This behavior incurs energy costs as evidenced by immune deficits and shorter life-spans in reproducing beetles. In the absence of an assembled transcriptome, relatively little is known concerning the molecular biology of these beetles. This work details the assembly and analysis of the Nicrophorus orbicollis transcriptome at multiple developmental stages. RNA-Seq reads were obtained by next-generation sequencing and the transcriptome was assembled using the Trinity assembler. Validation of the assembly was performed by functional characterization using Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Differential expression analysis highlights developmental stage-specific expression patterns, and immunity-related transcripts are discussed. The data presented provides a valuable molecular resource to aid further investigation into immunocompetence throughout this organism's sexual development.
Other authorsSee publication -
De novo Assembly and Analysis of the Chilean Pencil Catfish Trichomycterus areolatus Transcriptome
Journal of Genomics
Additional Authors: Nicolas Gouin, Alan S. Kolok, Paul H. Davis
Trichomycterus areolatus is an endemic species of pencil catfish that inhabits the riffles and rapids of many freshwater ecosystems of Chile. Despite its unique adaptation to Chile's high gradient watersheds and therefore potential application in the investigation of ecosystem integrity and environmental contamination, relatively little is known regarding the molecular biology of this environmental sentinel. Here, we detail the…Additional Authors: Nicolas Gouin, Alan S. Kolok, Paul H. Davis
Trichomycterus areolatus is an endemic species of pencil catfish that inhabits the riffles and rapids of many freshwater ecosystems of Chile. Despite its unique adaptation to Chile's high gradient watersheds and therefore potential application in the investigation of ecosystem integrity and environmental contamination, relatively little is known regarding the molecular biology of this environmental sentinel. Here, we detail the assembly of the Trichomycterus areolatus transcriptome, a molecular resource for the study of this organism and its molecular response to the environment. RNA-Seq reads were obtained by next-generation sequencing with an Illumina® platform and processed using PRINSEQ. The transcriptome assembly was performed using TRINITY assembler. Transcriptome validation was performed by functional characterization with KOG, KEGG, and GO analyses. Additionally, differential expression analysis highlights sex-specific expression patterns, and a list of endocrine and oxidative stress related transcripts are included.Other authorsSee publication
Honors & Awards
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Harvard Horizons Scholar
Harvard Graduate School of Arts and Sciences
Selected by the Graduate School of Arts and Sciences for the 2022 cohort, comprising seven PhD candidates chosen from among the 57 GSAS programs. Scholars receive in-depth, personalized training and coaching, culminating in presentation of their dissertation research at the Harvard Horizons Symposium in Sanders Theatre.
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NSF Graduate Research Fellowship
National Science Foundation
The National Science Foundation Graduate Research Fellowship Program (GRFP) recognizes and supports outstanding graduate students in NSF-supported STEM disciplines who are pursuing research-based master's and doctoral degrees at accredited United States institutions.
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Herchel Smith Graduate Fellowship
Harvard Graduate School of Arts and Sciences
Awarded by the Graduate School of Arts and Sciences to six incoming Harvard Integrated Life Sciences students with the aim of promoting scientific inquiry and collaboration among PhD students at Harvard University and the University of Cambridge.
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James Turpen INBRE Scholar Excellence Award
Nebraska IDeA Networks of Biomedical Research Excellence (INBRE) Program
Awarded by the Nebraska INBRE Program to an INBRE Scholar who has completed the program and has been accepted by a graduate school for a PhD program.
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Marcus L. Urann Fellowship
The Honor Society of Phi Kappa Phi
National fellowship awarded by the Honor Society of Phi Kappa Phi to six students in the United States entering their first year of graduate or professional training. Endowed through a Yoerger Presidential Fellowship, which is awarded each year to a student in one of the basic science disciplines.
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Barry M. Goldwater Scholarship
Barry M. Goldwater Scholarship and Excellence in Education Foundation
National scholarship awarded by the Board of Trustees of the Barry M. Goldwater Scholarship and Excellence in Education Foundation to ~300 undergraduate students in the United States intending to pursue a research career in a natural science, mathematics, or engineering.
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IDeA Networks of Biomedical Research Excellence (INBRE) Fellowship
University of Nebraska at Omaha and the National Institutes of Health
Awarded by the University of Nebraska at Omaha to four rising third-year undergraduates with the aim of underwriting the training of future biomedical researchers in the state of Nebraska. Funded through a grant awarded by the National Institutes of Health to a cohort of Nebraska colleges and universities.
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Regents Scholarship
University of Nebraska Board of Regents
Full-tuition merit-based scholarship awarded by the University of Nebraska Board of Regents for the duration of undergraduate studies.
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