Welcome

Our lab studies how pathogens evolve and spread. We use experimental and computational tools to test our hypotheses, and collaborate with clinical and public health institutions. We focus on questions of antibiotic resistance, within-host evolution and between-host transmission, and pathogen response to host immune pressures. Our overall aim is to improve diagnostics, therapeutics, and clinical and public health strategies to aid in the control of infectious diseases.

Updates from the Lab

May 2019 A preprint of Katie’s paper on TnSeq in multiple strains of S. aureus is now up on biorxiv. Using transposons with outward-facing promoters, she shows how gene essentiality varies across S. aureus strains under baseline growth conditions, but that under daptomycin exposure some of those variable genes/pathways (e.g., lipoteichoic acid synthesis) become consistently essential. Great work, Katie and team!

May 2019 Great work by Brian Arnold using N. gonorrhoeae datasets to investigate linkage and understand what has given rise to the particular patterns we see — there’s a lot more coupling linkage than expected at close distances (gonococcus is not quite as panmictic as previously thought!), and this close-distance coupling linkage is driven by a small fraction of genes undergoing either adaptive interspecies admixture (hello, commensal Neisseria) or balancing selection. Exciting to use genomics to uncover the forces shaping the gonococcal genome!

May 2019 A new publication led by Scott on antibiotic prescribing, looking at the cumulative probability of prescribing over 4 years. We described previously that 10% of the population accounts for 57% of the outpatient antibiotic prescribing and that 1/3 of the population gets a prescription each year; is it the same 1/3 from year to year? Here we show that after 4 years around 60% of the population received an antibiotic prescription and that this is reaching an apparent asymptote.

May 2019 A new manuscript from Sam and co. demonstrating a novel pathway to ceftriaxone (CRO) resistance in clinical isolates of Neisseria gonorrhoeae. Most CRO resistant isolates have penA mutations, but not all. Here we dig into those that have unexplained resistance, and we show resistance arose via mutations in rpoD and rpoB (components of RNA polymerase holoenzyme), that this has happened multiple times in clinical gonococcal populations, & multiple lineages of N. gonorrhoeae are a single mutation from CRO resistance.

Apr 2019 Congrats to Allie on her preprint, asking how much performance and reliability of machine learning-based prediction of AMR phenotype from genome seqs depend on dataset biases, resistance metrics, antibiotic-bacteria pairs, ML methods, parameters, etc. Answer: a lot!

Apr 2019 In a collaboration with colleagues at Massachusetts Department of Public Health, we used insurance claims data to look at trends in antibiotic prescribing in MA from 2011-15, now published in Open Forum Infectious Diseases. Prescribing decreased markedly! Raises lots of interesting hypotheses about what might explain these changes and the impact on resistance.

Apr 2019 A commentary by Scott and Yonatan on bystander selection in gonococcus is now published in the Journal of Infectious Diseases. How much bystander selection is there? How do we quantify it? What’s the relative impact of direct vs bystander selection for each drug? Lots of questions we need to consider that play into how we approach the problems of antimicrobial resistance generally.

Mar 2019 Hurray for Kevin on passing his PQE!

Mar 2019 Congratulations to Jess on being named a Harvard College PRISE (Program for Research in Science and Engineering) fellow for this summer!

Mar 2019 Thanks so much to the Broad Institute for the BroadIgnite award! I’m very excited for the support for this project!

Feb 2019 Thrilled for Crista, who will become an assistant professor at the Rochester Institute of Technology starting this summer! Very proud and excited to see you achieve exactly what you aimed to do when you started as a post-doc!

Feb 2019 Congratulations to Mohamad, who has accepted an offer at Day Zero Diagnostics for a position as Senior Computational Biologist. Bittersweet, but we’re excited for your new venture!

Feb 2019 A new manuscript from Scott in which we use modeling and empirical data to start to tackle the following questions: what’s the right geographic scale to test outpatient antibiotic stewardship interventions? How much does spillover from neighbors impact results?

Feb 2019 Crista’s new pre-print on developing RNA-based diagnostics for antibiotic resistance detection in gonococcus and the importance of considering population structure in doing so is now up on bioRxiv. Great work, Crista!

Jan 2019 Yonatan had a great time visiting the Institute of Microbiology and Infection at the University of Birmingham, catching up with colleagues and friends, and meeting new ones. Thanks for having me!

Jan 2019 Hurray for Scott, who accepted a job offer as Scientific Director at OpenBiome! The lab will miss you, but we’re excited to see the amazing things you’ll do!

Dec 2018 Congrats to Scott and our co-authors on the publication of The distribution of antibiotic use and its association with antibiotic resistance in eLife! We show: 10% of the population in the US uses 57% of the antibiotics; around 1/3 of people take an antibiotic every year; for most of 72 pairs of antibiotics and bacteria, there’s a positive correlation between use and resistance across the US; breadth of use (the fraction of the population consuming antibiotics) is more positively associated than repeat use with resistance in a population.

Dec 2018 Yonatan gave a keynote lecture at the One2Many systems biology conference at the Weizmann Institute. Such an honor to be invited by the graduate students!

Nov 2018 Allison and Kevin both spoke at the Wellcome Genome Campus meeting on “Antimicrobial Resistance – Genomes, Big Data and Emerging Technologies” — and Kevin received a commendation for his talk. Well done, Allie and Kevin!

Nov 2018 Yonatan gave a lecture in the NDPIA/IBA course on ”Antibiotics and Antibiotic Resistance” at Hjortviken, Hindås / Gothenburg. Great course, wonderful students and faculty.

Nov 2018 The 2nd SMBE satellite workshop on pathogen genomics was fantastic! A community of scientists and public health folks, all eager to apply innovations in genomics to disease control. Thanks so much to the organizers for the invitation and opportunity to participate!

Oct 2018 Yonatan visited NYC for the Doris Duke Charitable Foundation Clinical Scientist Developmental Award meeting — inspiring to hear about a lot of exciting science, meet new colleagues, and catch up with old friends.

Oct 2018 Yonatan had a great trip to Indiana University School of Medicine — thanks, Dave Nelson, for the invite! Fun to learn more about the exciting ongoing work, meet colleagues, and share what we’re up to.

Sept 2018 Kevin and Yonatan attended the International Pathogenic Neisseria Conference, where Kevin presented a poster of his GWAS work, and Yonatan had the pleasure of presenting work by Sam and Crista. Great conference, wonderful community.

Sept 2018 Scott’s paper on racial/ethnic disparities in antibiotic use, using MEPS 2014-15 survey of prescription fill rates, is now up at Emerging Infectious Diseases. Whites use more antibiotics (across all classes) than all other races/ethnicities. Raises many questions, including how this may impact on emergence and spread of AMR.

Sept 2018 New preprint up on bioRxiv, in which we present a Bayesian model of acquisition and clearance of bacterial colonization, with the goal of improving on the heuristic SNP distance often used to say whether two isolates represent the “same” strain. Great work led by Marko Järvenpää and together with Pekka Marttinen and a wonderful group of collaborators.

Sept 2018 Scott’s paper on azithromycin susceptibility in gonococcus and seasonal macrolide use is now out at the Journal of Infectious Diseases. Highlighted in CIDRAP!

Aug 2018 Scott and Yonatan attended and spoke at the STD Prevention Conference, with Scott talking about his project investigating the relationship between seasonal variations in azithromycin prescribing and resistance in gonococcus and Yonatan presenting on modeling to help slow and control the spread of resistance. CDC colleagues presented data showing a continued and marked increase in rates of gonorrhea and the extent of resistance — lots of work to do!

Aug 2018 Crista’s paper on gonococcal acquisition of azithromycin resistance through interspecies recombination (and a lot of great work exploring epistasis and integrating population genomics and basic microbiology) is now out at mBio. Highlighted in an accompanying commentary!

July 2018 Scott’s paper on trends in antibiotic prescribing in the elderly is now out at BMJ.

June 2018 Yonatan gave a talk on mumps at the Virus Genomics and Evolution meeting at the Wellcome Genome Campus. Excellent meeting!

June 2018 Tatum and Yonatan’s review on genomics and MDR gonococci is now out.

Apr 2018 Congratulations to both Daphne and Allison on passing their PQEs!

Mar 2018 Our paper on the resurgence of mumps in highly vaccinated populations is now out in Science Translational Medicine.

Feb 2018 Our paper on why the influenza H3N2 vaccine effectiveness in the 2012-13 season was modest at best is now out in CID.

Feb 2018 Yonatan visited EBI and the Wellcome Sanger Institute — had a great time visiting folks and giving a talk!

Feb 2018 Yonatan participated in a panel discussion about the flu season — thanks very much to the folks at The Forum at HSPH!

Feb 2018 Dan Rubin from the MD-PhD program is rotating in the lab. Welcome, Dan!

Nov 2017 Congrats to Sanjat, whose paper just came out in JCM!

Oct 2017 Yonatan gave a talk in the 116th International Titisee Conference, a conference titled, “From pathogen evolution to microbiome dynamics”. A great group of people, lots of exciting science.

Oct 2017 Yonatan gave a keynote talk at the ASM conference on rapid applied microbial sequencing and bioinformatics pipelines. Notes on the talks from this conference can be found here.

Sept 2017 Congratulations to Kevin, whose undergraduate thesis work was just published!

Sept 2017 Now on bioRxiv: work with Joe Lewnard on what explains the resurgence of mumps in the US. Our take: it’s waning vaccine induced immunity.

Sept 2017 Welcome to new post-doc Tatum Mortimer, bringing her bioinformatics and pathogen genomics expertise to the lab! We’re excited to have you join the group!

Aug 2017 A new paper from the lab, working closely with Ashleigh Tuite and colleagues from the Prevention Policy Modeling Lab to investigate the potential impact of rapid diagnostics on antibiotic resistance in gonorrhea.

August 2017 Welcome to Yi Wang, who has joined the lab as a research assistant!

August 2017 New paper on the intrahost diversity of respiratory syncytial virus (RSV) over the course of individual infections in experimentally infected healthy adults and naturally infected infants; building on our prior work in collaboration with colleagues at the Broad Institute and the DeVincenzo lab at UTHSC.

July 2017 New paper reporting genome sequence of an enterovirus from CSF of a patient with orchitis and aseptic meningitis — bringing genomics into the clinical lab! Fun collaboration with the Sabeti lab, among others at the Broad Institute and BWH/MGH.

July 2017 At the STI & HIV World Conference, Yonatan gave a talk entitled, “Integrating population genomics and mathematical modeling to control antibiotic resistance in gonococcus,” as part of the symposium on “Mathematical modeling and decision making in the world of STIs.”

July 2017 Lucas Buyon from the Biological Sciences in Public Health  program is rotating in the lab. Welcome, Lucas! And to our delight, Kevin Ma, now also in BPH, is doing his first rotation with us.

July 2017 From project started a few years ago with Sarah Cobey, and done in collaboration with Scott Hensley, and colleagues at JCVI, UChicago, Boston Children’s Hospital, and Stanford, our bioRxiv preprint: Despite egg-adaptive mutations, the 2012-13 H3N2 influenza vaccine induced comparable antibody titers to the intended strain

May 2017 Yonatan had a fantastic visit to the University of Oslo — thanks to Mike Koomey for hosting and his amazing hospitality!

April 2017  A BioRxiv preprint of great work from Sanjat and a number of great lab members and colleagues: Increasing Antibiotic Susceptibility In Staphylococcus aureus In Boston, Massachusetts, 2000-2014: An Observational Study

April 2017 Our first BioRxiv preprint: the impact of rapid susceptibility testing and antibiotic selection strategy on the emergence and spread of antibiotic resistance in gonorrhea — great work with Ashleigh Tuite and colleagues!

March 2017 Debra Van Egeren from the Systems Biology program is rotating in the lab. Welcome, Debra!

March 2017 Hurray, Kevin! We’re delighted that Kevin won an NSF Graduate Research Fellowship. Well done!

March 2017 Congratulations to Sanjat, selected to be the Clinical Microbiology Fellow at Brigham and Women’s Hospital starting in July!

February 2017 Yonatan spoke at the US-Japan Cooperative Medical Sciences Program 2017 meeting in Seoul.

January 2017 Jacob Shenker from the Systems Biology program is rotating in the lab. Welcome, Jacob!

January 2017 Adam Nitido, a graduate student in the Harvard Virology PhD program, is doing a rotation in the lab. Welcome, Adam!

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