About

Conor Walsh is the Paul A. Maeder Professor of Engineering and Applied Sciences at Harvard University, affiliated with the Harvard John A. Paulson School of Engineering and Applied Sciences. He is also an Associate Faculty Member at the Wyss Institute for Biologically Inspired Engineering. His primary teaching area includes Materials Science & Mechanical Engineering. Walsh's research focuses on bioinspired robotics and computing, biomechanics and motor control, and the development of wearable devices and robotic systems that enhance human capabilities. His work involves applying principles from applied mathematics, data science, and artificial intelligence to model physical and biological phenomena, with particular emphasis on health, medicine, and human-computer interaction. Through his lab, Walsh advances innovations in materials, robotics, and control systems aimed at improving human health and performance.

Research topics

• Chemistry
• Biochemistry
• Computer Science
• Biology
• Biochemical engineering
• Engineering
• Organic chemistry
• Polymer science
• Data science
• Bioinformatics
• Computational biology
• Philosophy
• Risk analysis (engineering)
• Biotechnology
• Medicine
• Business
• Pharmacology

Selected publications

• Development of a Working Definition of Severe Von Willebrand Disease

  Blood · 2024-11-05 · 3 citations

  articleOpen access

  Introduction: von Willebrand Disease (VWD) is a heterogeneous disorder resulting from abnormalities of quantity and function of von Willebrand factor (VWF). The primary symptom of bleeding may manifest in different degrees ranging from mild to severe. The diagnosis and management of severe patients presents with challenges and may require a unique approach that is supported by the ASH ISTH NBDF WFH 2021 guidelines on the management of von Willebrand disease in its recommendation which states “In patients with VWD with a history of severe and frequent bleeds, the guideline panel suggests using long-term prophylaxis rather than no prophylaxis.” Definitions and criteria identifying this group of severe patients vary, taking into account bleeding symptoms, functional level, diagnostic VWD classification, and genetic findings, without meeting any specific standard that would be ideal. This project seeks to establish a working definition of severe von Willebrand disease by consensus amongst a group of experts on VWD. Method: A panel of experts were first identified. A total of 23 individuals were invited, with 17 experts agreeing to participate and contribute their opinion. The panel represented a diverse opinion with 14 residing in North America, 2 in Europe, and 1 in Asia, and consisted of 12 physicians, 4 doctoral experts, 4 patients or family members, and 2 with other fields of expertise. A modified Delphi method was selected to establish a consensus. Responses were shared with everyone, although those providing the responses were able to remain anonymous to the rest of the panel. Modification to the methodology included using electronically disseminated surveys to gather opinions in each round and to anonymously share everyone's comments. An initial meeting occurred at the outset to establish the fields and identify the potential criterion within each field that would become the subject for questioning. Questionnaires probed criterion that potentially could be utilized in a definition from each of the fields of genetics, diagnostic classification, functional laboratory results, and clinical bleeding symptoms and a summary of the responses after each round was completed. Each round of question and answers were disseminated sequentially with the subsequent round narrowed and focused by the previous round. Each expert's opinion was summarized to prevent it from interfering with the other expert's opinion. A predefined criteria of 80% concurring opinions established a consensus. Results: The first round established that 1) genetics alone is currently not enough to establish a patient as having severe disease, 2) no diagnostic classification of VWD was sufficient to determine severe disease and 3) any VWD type may be severe or be at risk for severe symptoms, responding most Type 3 VWD are severe (but not all), many Type 2 VWD are severe, and some Type 1 VWD are severe. A preliminary draft definition was created for the summary and a second-round questionnaire was dispersed to further refine it. The second and final round resulted in the following working definition of severe von Willebrand disease: A. Anyone meeting the diagnostic classification for von Willebrand disease AND B. Any VWF antigen or activity: Result <20% regardless of bleeding phenotype Or Result <30% with excessive bleeding symptoms including: a. Bleeding that resulted in hospitalization, required surgical procedure, red blood cell transfusion, Hemoglobin decrease >2g/dL, or b. Intracranial, intraspinal, pericardial, retroperitoneal, intramuscular bleeding with compartment syndrome, or c. Persistent or recurrent bleeding that is disruptive of work or school. Conclusion: von Willebrand disease is a heterogeneous disorder in which management and treatment of the group of patients with severe disease requires a very different approach; however, no specific or uniform standards exist for defining this patient group. This project creates a working consensus definition of severe von Willebrand disease, being vetted by ISTH Scientific and Standardization Committee, which will allow for consistent identification and therefore improved and more effective care of this population.

  PublisherOA PDFDOI

• Predictability of European winter 2022/23

  Atmospheric Science Letters · 2024-10-22 · 1 citations

  articleOpen accessSenior author

  Abstract The boreal winter of 2022/23 was notable as a third consecutive winter in which La Niña had an influence on the European weather. The GloSea6 seasonal forecast system predicted a blocked circulation pattern in the North Atlantic in early winter (December), and then a transition through mid‐winter (January) into a more zonal pattern in late winter (February), consistent with the canonical La Niña teleconnection pattern seen previously. The seasonal forecast for the UK was an increased likelihood of near average temperatures, and drier‐ and calmer‐than‐average conditions. Both the predicted broad‐scale circulation patterns and UK winter mean weather conditions verified well against observations, and we show that seasonal forecasts of the North Atlantic Oscillation (NAO) over the last 10 winters show similar skill to previously reported hindcasts. Throughout the winter, the Madden–Julian Oscillation (MJO) was particularly active. On three occasions, it exhibited strong phases 6 and 7. There was also a sudden stratospheric warming (SSW) that occurred on 16th February. This was followed by colder conditions and associated impacts similar to the canonical negative NAO response over the UK, although the main impact fell in March and so did not affect the winter (December–January–February) mean conditions.

  PublisherOA PDFDOI

• New Insights into the Mechanism of Action of L-681,217, a Medicinally Promising Polyketide Inhibitor of Bacterial Protein Translation

  Biochemistry · 2024-11-22 · 2 citations

  articleOpen access

  An attractive strategy for combating antibacterial resistance involves the development of new antibiotics whose mechanisms differ from those of existing ones in the clinic. Elfamycin antibiotics, whose prototypes include kirromycin and aurodox, are illustrative examples based on their ability to target EF-Tu, an essential component for protein translation in bacteria. Our efforts to revisit this antibiotic class were enabled by two developments. First, we produced L-681,217, an understudied member of this polyketide family harboring a terminal carboxylic acid in place of a hydroxypyridone ring, and synthesized a biotinylated derivative with comparable activity to the natural product. Second, we established a sensitive cell-free protein synthesis (CFPS) assay in which superfolder green fluorescent protein (sfGFP) production was inhibited by L-681,217. Biotinyl-L-681,217 was used to drain the CFPS system of endogenous EF-Tu, allowing replenishment with orthologs to interrogate pathogen selectivity and propensity toward resistance. Comparative in vitro analysis of kirromycin and L-681,217 showed that, while both antibiotics are equipotent in CFPS assays, they interact distinctly with purified EF-Tu, a feature that presumably correlates with prior observations that kirromycin enhances GTP hydrolysis by EF-Tu whereas L-681,217 does not. Analysis of L-681,217 and kirromycin accumulation in selected mutant E. coli strains also revealed that antibiotic import and efflux contributed to resistance. The promise of L-681,217 as a medicinal lead was underscored by the observation that, unlike aurodox, this polyketide does not inhibit adenylosuccinate synthase.

  PublisherOA PDFDOI

• THE POWER OF CONTINUING MEDICAL EDUCATION IN ADDRESSING THE UNMET NEEDS OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

  Journal of the American College of Cardiology · 2023-03-01

  articleOpen accessSenior author
  PublisherDOI

• The Chemical Biology of Carbon

  2023-03-29 · 2 citations

  book1st authorCorresponding

  Building upon the previous volumes, The Chemical Biology of Sulfur, The Chemical Biology of Phosphorus, and The Chemical Biology of Nitrogen, this book examines the organic chemistry of life, The Chemical Biology of Carbon. It examines chemical biology open to carbon-containing natural metabolites that allow both retrospective and predictive behaviours of both biosynthetic and degradative metabolism in primary and secondary pathways. This book also notes the centrality of a core set of heterocycles in metabolites and coenzyme forms of vitamins and how that chemistry enables life. The organic chemical fundamental considerations are always tied to specific metabolites and metabolic transformations. This context makes this volume not a classical organic or even bioorganic approach to organic chemistry in vivo but instead a unique analysis of how the rules and reactivities of organic chemistry underlie the organic chemistry of life. The Chemical Biology of Carbon is an ideal reference and guide for medicinal chemists, chemical biologists, organic chemists as well as postgraduate, graduate and advanced undergraduate students in these areas and related disciplines.

  PublisherDOI

• Covalent Catalytic Strategies for Enzymes That Modify RNA Molecules on their Tripartite Building Blocks

  ACS Chemical Biology · 2022-09-14 · 5 citations

  review1st authorCorresponding

  The tripartite structures of the four 5′-nucleotide monophosphate (NMP) building blocks in all RNAs enable enzyme-catalyzed chemical modifications to three types of sites: the heterocyclic bases via N- and C-methylations and other alkylations, conversion of the N-glycoside linkages of the uridine moiety to the C–C glycoside link in pseudouridines, and the phosphodiester-mediated processes of 5′-capping, splicing, and 3′-tailing of premRNAs. We examine known cases for enzymatic covalent catalytic strategies that entail transient formation and breakdown of covalent enzyme–RNA adducts in each catalytic cycle. One case involves generation of the required carbon nucleophile during C5 methylation of cytosine residues in RNAs. A second examines the mechanism proposed for pseudouridine synthases and for replacement of a guanine residue in tRNAs by queuosine. The third category involves phosphoric anhydride and phosphodiester chemistry by which viral RNAs encode enzymes for making their own mRNA 5′-caps. This strategy includes the recent finding that the SARS-CoV2 proteins assemble a canonical 5′,5′-GTP cap on their 28 900 nucleotide genomic RNA to enable its translation as an mRNA by host translational machinery by way of a covalent RNA–viral enzyme intermediate.

  PublisherDOI

• Propofol: Milk of Amnesia

  Cell · 2022-12-01 · 4 citations

  erratumOpen access1st authorCorresponding
  PublisherOA PDFDOI

• World Bank speeds Africa’s COVID vaccination

  Nature · 2022-04-26

  letter1st authorCorresponding
  PublisherDOI

• Natural Product Biosynthesis

  2022-12-14 · 41 citations

  bookOpen access1st authorCorresponding

  Authored by leading experts in the enzymology of natural product biosynthesis, this completely revised and updated edition provides a description of the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era. Although some 500 000 – 600 000 natural products have been isolated and characterized over the past two centuries, there may be a 10-fold greater inventory awaiting immediate exploration based on biosynthetic gene cluster predictions. The approach of this book is to codify the chemical logic that underlies each natural product structural class as they are assembled from building blocks of primary metabolism. This second edition integrates many new findings into the sets of principles of the first edition that parsed categories of natural product chemistries into the underlying enzymatic mechanisms and the catalytic machinery for building the varied and complex end product metabolites. New chapters include evaluation of a core set of thermodynamically activated but kinetically stable metabolites that power both primary and secondary metabolic pathways. Also, after decades of uncertainty about the existence of various pericyclase classes, a series of genome mining, heterologous expression, and enzymatic activity characterization have validated a plethora of pericyclases over the past decade. The several types of pericyclases are involved in biosynthetic complexity generation of almost every major category of natural products. This text will serve as a reference point for chemists of every subdiscipline, including synthetic organic chemists and medicinal chemists. It will also be valuable to bioinformatic and computational biologists, pharmacognocists and chemical ecologists, and bioengineers and synthetic biologists.

  PublisherOA PDFDOI

• Tailoring enzyme strategies and functional groups in biosynthetic pathways

  Natural Product Reports · 2022-10-21 · 40 citations

  review1st authorCorresponding

  Secondary metabolites are assembled by drawing off and committing some of the flux of primary metabolic building blocks to sets of enzymes that tailor the maturing scaffold.

  PublisherDOI

Recent grants

• NIH Grant P01GM047467

  NIH · $55.8M · 2019

• Medical Scientist Training Program

  NIH · $64.1M · 1979–2022

• NIH Grant R01GM021643

  NIH · $2.3M · 1993

• Training in Pharmacological Sciences

  NIH · $9.1M · 1975–2019

• NIH Grant R01GM020011

  NIH · $10.3M · 2015

Frequent coauthors

• Neil L. Kelleher

  Northwestern University

  110 shared

• Chaitan Khosla

  Stanford University

  62 shared

• Michael A. Fischbach

  Stanford University

  61 shared

• Daniel Kahne

  Harvard University

  55 shared

• J. Martin Bollinger

  Pennsylvania State University

  52 shared

• Mohamad Mouchli

  Cleveland Clinic

  44 shared

• Bruce Furie

  41 shared

• Shravani Reddy

  40 shared