Scientific Analyst at Morrison & Foerster LLP
Los Angeles, California, United States
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Activity
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Finally, defended! The total journey has been anything but easy; it was filled with countless late nights, rigorous research, and moments of doubt.…
Finally, defended! The total journey has been anything but easy; it was filled with countless late nights, rigorous research, and moments of doubt.…
Liked by Kristen Muñoz, Ph.D.
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Our Profile of the Month is Marya Ornelas, a PhD student in chemical biology, who is involved in mentoring students through the Chemical Science…
Our Profile of the Month is Marya Ornelas, a PhD student in chemical biology, who is involved in mentoring students through the Chemical Science…
Liked by Kristen Muñoz, Ph.D.
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The American Chemical Society has awarded Rebecca Ulrich of the University of Illinois Urbana-Champaign the 15th Irving S. Sigal Postdoctoral…
The American Chemical Society has awarded Rebecca Ulrich of the University of Illinois Urbana-Champaign the 15th Irving S. Sigal Postdoctoral…
Liked by Kristen Muñoz, Ph.D.
Experience
Education
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University of Illinois Urbana-Champaign
Doctor of Philosophy - PhD Chemistry
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Activities and Societies: NIH Chemical Biology Interface Trainee
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Publications
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A Gram-negative-selective antibiotic that spares the gut microbiome
Nature
Infections caused by Gram-negative pathogens are increasingly prevalent and are typically treated with broad-spectrum antibiotics, resulting in disruption of the gut microbiome and susceptibility to secondary infections. There is a critical need for antibiotics that are selective both for Gram-negative bacteria over Gram-positive bacteria, as well as for pathogenic bacteria over commensal bacteria. Here we report the design and discovery of lolamicin, a Gram-negative-specific antibiotic…
Infections caused by Gram-negative pathogens are increasingly prevalent and are typically treated with broad-spectrum antibiotics, resulting in disruption of the gut microbiome and susceptibility to secondary infections. There is a critical need for antibiotics that are selective both for Gram-negative bacteria over Gram-positive bacteria, as well as for pathogenic bacteria over commensal bacteria. Here we report the design and discovery of lolamicin, a Gram-negative-specific antibiotic targeting the lipoprotein transport system. Lolamicin has activity against a panel of more than 130 multidrug-resistant clinical isolates, shows efficacy in multiple mouse models of acute pneumonia and septicaemia infection, and spares the gut microbiome in mice, preventing secondary infection with Clostridioides difficile. The selective killing of pathogenic Gram-negative bacteria by lolamicin is a consequence of low sequence homology for the target in pathogenic bacteria versus commensals; this doubly selective strategy can be a blueprint for the development of other microbiome-sparing antibiotics.
Other authorsSee publication -
Computational discovery of dynobactin antibiotics
Nature Microbiology
A computational analysis of biosynthetic gene clusters with unique structural features unveils new natural product scaffolds, leading to the discovery of an antibiotic targeting BamA with activity against Gram-negative pathogens.
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An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections
ACS Central Science
Genomic studies and experiments with permeability-deficient strains have revealed a variety of biological targets that can be engaged to kill Gram-negative bacteria. However, the formidable outer membrane and promiscuous efflux pumps of these pathogens prevent many candidate antibiotics from reaching these targets. One such promising target is the enzyme FabI, which catalyzes the rate-determining step in bacterial fatty acid biosynthesis. Notably, FabI inhibitors have advanced to clinical…
Genomic studies and experiments with permeability-deficient strains have revealed a variety of biological targets that can be engaged to kill Gram-negative bacteria. However, the formidable outer membrane and promiscuous efflux pumps of these pathogens prevent many candidate antibiotics from reaching these targets. One such promising target is the enzyme FabI, which catalyzes the rate-determining step in bacterial fatty acid biosynthesis. Notably, FabI inhibitors have advanced to clinical trials for Staphylococcus aureus infections but not for infections caused by Gram-negative bacteria. Here, we synthesize a suite of FabI inhibitors whose structures fit permeation rules for Gram-negative bacteria and leverage activity against a challenging panel of Gram-negative clinical isolates as a filter for advancement. The compound to emerge, called fabimycin, has impressive activity against >200 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, and does not kill commensal bacteria. X-ray structures of fabimycin in complex with FabI provide molecular insights into the inhibition. Fabimycin demonstrates activity in multiple mouse models of infection caused by Gram-negative bacteria, including a challenging urinary tract infection model. Fabimycin has translational promise, and its discovery provides additional evidence that antibiotics can be systematically modified to accumulate in Gram-negative bacteria and kill these problematic pathogens.
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Facilitating Compound Entry as a Means to Discover Antibiotics for Gram-Negative Bacteria
Accounts of Chemical Research
It has been over half a century since the last class of antibiotics active against the most problematic Gram-negative bacteria was approved by the Food and Drug Administration (FDA). The major challenge with developing antibiotics to treat these infections is not drug-target engagement but rather the inability of most small molecules to traverse the Gram-negative membranes, be retained, and accumulate within the cell. Despite an abundance of lead compounds, limited understanding of the…
It has been over half a century since the last class of antibiotics active against the most problematic Gram-negative bacteria was approved by the Food and Drug Administration (FDA). The major challenge with developing antibiotics to treat these infections is not drug-target engagement but rather the inability of most small molecules to traverse the Gram-negative membranes, be retained, and accumulate within the cell. Despite an abundance of lead compounds, limited understanding of the physicochemical properties needed for compound accumulation (or avoidance of efflux) in Gram-negative bacteria has precluded a generalizable approach for developing Gram-negative antibiotics. Indeed, in many instances, despite years of intensive derivatization efforts and the synthesis of hundreds of compounds aimed at building in Gram-negative activity, little or no progress has been made in expanding the spectrum of activity for many Gram-positive-only antibiotics. In this Account, we describe the discovery and successful applications of a promising strategy for enhancing the accumulation of Gram-positive-only antibiotics as a means of imbuing compounds with broad-spectrum activity.Utilizing a prospective approach examining the accumulation in Escherichia coli for more than 180 diverse compounds, we found that small molecules have an increased likelihood to accumulate in E. coli when they contain an ionizable Nitrogen, have low Three-dimensionality, and are Rigid. Implementing these guidelines, codified as the "eNTRy rules" and assisted by web application www.entry-way.org, we have facilitated compound entry and systematically built Gram-negative activity into Gram-positive-only antibiotics. Though each antibiotic will have case-specific considerations, we describe a set of important criteria to consider when selecting candidate Gram-positive-only antibiotics for conversion to Gram-negative-active versions via the eNTRy rules.
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Configurable lipid membrane gradients quantify diffusion, phase separations and binding densities
Soft Matter
Single-experiment analysis of phospholipid compositional gradients reveals diffusion coefficients, phase separation parameters, and binding densities as a function of localized lipid mixture. Compositional gradients are formed by directed self assembly where rapid-prototyping techniques (i.e., additive manufacturing or laser-cutting) prescribe lipid geometries that self-spread, heal and mix by diffusion.
More activity by Kristen
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Okay, I’m very excited to share that I’ve recently published two articles, which represent one of the major parts of my Ph.D. work. These papers…
Okay, I’m very excited to share that I’ve recently published two articles, which represent one of the major parts of my Ph.D. work. These papers…
Liked by Kristen Muñoz, Ph.D.
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Deze studie in Nature van Kristen Muñoz, Ph.D. Muñoz et al. laat een hoopvolle ontwikkeling zien: een antibioticum dat darm-microbioom-sparend te…
Deze studie in Nature van Kristen Muñoz, Ph.D. Muñoz et al. laat een hoopvolle ontwikkeling zien: een antibioticum dat darm-microbioom-sparend te…
Liked by Kristen Muñoz, Ph.D.
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Our body is home to billions of gut bacteria that are beneficial to our daily functions. 🦠 But some of the more powerful antibiotics kill both the…
Our body is home to billions of gut bacteria that are beneficial to our daily functions. 🦠 But some of the more powerful antibiotics kill both the…
Liked by Kristen Muñoz, Ph.D.
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MoFo’s Intellectual Property Group was recognized in 11 practice areas, with 27 lawyers achieving 33 recognitions in the 2024 edition of IAM Patent…
MoFo’s Intellectual Property Group was recognized in 11 practice areas, with 27 lawyers achieving 33 recognitions in the 2024 edition of IAM Patent…
Liked by Kristen Muñoz, Ph.D.
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Congratulations to MoFo's Patent Strategy + Prosecution Practice for being recognized once again by Chambers USA as Band 1 for Patent Prosecution…
Congratulations to MoFo's Patent Strategy + Prosecution Practice for being recognized once again by Chambers USA as Band 1 for Patent Prosecution…
Liked by Kristen Muñoz, Ph.D.
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Congratulations to MoFo's Patent Strategy + Prosecution Practice for being recognized once again by Chambers USA as Band 1 for Patent Prosecution…
Congratulations to MoFo's Patent Strategy + Prosecution Practice for being recognized once again by Chambers USA as Band 1 for Patent Prosecution…
Liked by Kristen Muñoz, Ph.D.
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Really excited to be able to share Eikon's first organic chemistry-related paper! It was a huge pleasure to work on this publication with a highly…
Really excited to be able to share Eikon's first organic chemistry-related paper! It was a huge pleasure to work on this publication with a highly…
Liked by Kristen Muñoz, Ph.D.
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What if there was an antibiotic that doesn't disrupt the gut microbiome? There is now. A discovery published at Nature today https://lnkd.in/g8D9hhTc
What if there was an antibiotic that doesn't disrupt the gut microbiome? There is now. A discovery published at Nature today https://lnkd.in/g8D9hhTc
Liked by Kristen Muñoz, Ph.D.
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I am thrilled to share that I successfully defended my doctoral dissertation and graduated with a PhD in Chemical Engineering from the University of…
I am thrilled to share that I successfully defended my doctoral dissertation and graduated with a PhD in Chemical Engineering from the University of…
Liked by Kristen Muñoz, Ph.D.
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A team led by Paul Hergenrother at the University of Illinois Urbana-Champaign has discovered a new antibiotic that exclusively targets gram-negative…
A team led by Paul Hergenrother at the University of Illinois Urbana-Champaign has discovered a new antibiotic that exclusively targets gram-negative…
Liked by Kristen Muñoz, Ph.D.
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