Malik Lab

Malik Lab Members

Kevin Forsberg

Background

Kevin grew up outside of Madison, Wisconsin and, like any good Wisconsinite, eats way too much cheese. He also maintains a reverent love of the Green Bay Packers, as is custom.

Kevin’s first research experience was at the Translational Genomics Research Institute in Phoenix, where he led an effort to identify copy number variation associated with autism spectrum disorders while an undergraduate at Arizona State University. After graduation, Kevin began his PhD work in the lab of Gautam Dantas at Washington University in St. Louis, researching antibiotic resistance genes in soil microbial communities. His worked focused on the potential for antibiotic resistance genes to move between innocuous soil bacteria and human pathogens as well as identifying the factors governing resistance gene composition in natural soil communities. He also discovered a new family of tetracycline-inactivating enzymes, demonstrating that these enzymes of oxidize tetracycline via a previously undescribed mechanism.

Research Interests

As he concluded his PhD work, Kevin became fascinated with phages as agents of horizontal gene transfer, which led to a broader interest in phage-bacterial conflicts. To prevent phage infection, bacteria have devised anti-phage defenses which has spurred phages to develop counter-defense strategies. This arms race has been raging for billions of years, which means there is a huge diversity of defense and counter-defense systems in nature – most of which have not been discovered! As a postdoc in the Malik lab, Kevin has focused on one aspect of this phage-bacterial arms race: how phages overcome CRISPR-Cas defenses in bacteria. He developed a functional selection scheme to find to CRISPR-Cas inhibitors from large DNA libraries (e.g. metagenomic libraries). Applied to human oral and fecal microbiomes, this selection revealed many new examples of these phage counter-defenses, including CRISPR-Cas inhibitors with new mechanisms. Kevin’s future lab will continue to use functional selections to reveal new bacterial defenses and phage counter-defenses, which he will pursue in mechanistic detail.

kevin_hiking

Publications

  • Forsberg KJ, Schmidtke DT, Werther R, Hausman D, Stoddard BL, Kaiser BK, Malik HS. AcrIIA22 is a novel anti-CRISPR that impairs SpyCas9 activity by relieving DNA torsion of target plasmids. BioRxiv. 2020, doi: 10.1101/2020.09.28.317578.
  • Forsberg KJ, Bhatt IV, Schmidtke DT, Javanmardi K, Dillard KE, Stoddard BL, Finkelstein IJ, Kaiser BK, Malik HS. Functional metagenomics-guided discovery of potent Cas9 inhibitors in the human microbiome. eLife. 2019; Sep 10(8): e46540. (PMID: 31502535)
  • Forsberg KJ, Malik HS. Microbial Genomics: The Expanding Universe of Bacterial Defense Systems. Current Biology. 2018; 28(8):R361-364.
  • Crofts TS, Wang B, Spivak A, Gianoulis TA, Forsberg KJ, Gibson MK, Johnsky LA, Broomall SM, Rosenzweig CN, Skowronski EW, Gibbons HS, Sommer MO, Dantas G. Shared strategies for β-lactam catabolism in the soil microbiome. Nature Chem Bio. 2018, doi: 10.1038/s41589-018-0052-1.
  • Xu Z, Stogios PJ, Quaile AT, Forsberg KJ, Patel S, Skarina T, Houliston S, Arrowsmith C, Dantas G, Savchenko A. Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes. ACS Infectious Diseases. 2017; 9(3), 653-665.
  • Crofts TS, Wang B, Spivak A, Gianoulis TA, Forsberg KJ, Gibson MK, Johnsky LA, Broomall SM, Rosenzweig CN, Skowronski EW, Gibbons HS, Sommer MO, Dantas G. Draft genome sequences of three β-lactam-catabolizing soil Proteobacteria. Genome Announcements. 2017; 32(5), e00653-17.
    Yoneda A, Henson WR, Goldner NK, Park KJ, Forsberg KJ, Kim SJ, Pesesky MW, Foston M, Dantas G, and Moon TS. Comparative transcriptomics elucidates adaptive phenol tolerance and utilization in lipid-accumulating Rhodococcus opacus PD630. Nucl. Acids Res, 2016; doi:10.1093/nar/gkw055
  • Forsberg KJ, Patel S, Witt E, Wang B, Ellison T, Dantas G. Identification of genes conferring tolerance to lignocellulose-derived inhibitors by functional selections in soil metagenomes. Appl Environ Microbiol, 2016; 82(2), 528-537.
  • Forsberg KJ, Patel S, Wencewicz TA, Dantas G. The tetracycline destructases: a novel family of tetracycline-inactivating enzymes. Chemistry & Biology, 2015; 22(7), 888-897.
  • Gibson MK, Forsberg KJ, Dantas G. Improved Annotation of Antibiotic Resistance Determinants Reveals Microbial Resistomes Cluster by Ecology. The ISME Journal. 2015; 9:207
  • Forsberg KJ, Patel S, Gibson MK, Lauber CL, Knight R, Fierer, N, Dantas G. Bacterial phylogeny structures soil resistomes across habitats. Nature. 2014; 509 (7502): 612.
  • Pehrsson EC, Forsberg KJ, Gibson MK, Ahmadi S, Dantas G. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs. Frontiers in Microbiology. 2013; 4(145).
  • Moore AM, Patel S, Forsberg KJ, Wang B, Bentley G, Razia Y, Qin X, Tarr PI, Dantas G. Pediatric Fecal Microbiota Harbor Diverse and Novel Antibiotic Resistance Genes. PLOS ONE. 2013; 8 (11): e78822.
  • Forsberg KJ, Reyes A, Wang B, Selleck EM, Sommer MO, Dantas G. The shared antibiotic resistome of soil bacteria and human pathogens. Science. 2012; 337(6098):1107-11.
  • Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C, Downey SL, Johnson BE, Fouse SD, Delaney A, Zhao Y, Olshen A, Ballinger T, Zhou X, Forsberg KJ, Gu J, Echipare L, O`Geen H, Lister R, Pelizzola M, Xi Y, Epstein CB, Bernstein BE, Hawkins RD, Ren B, Chung WY, Gu H, Bock C, Gnirke A, Zhang MQ, Haussler D, Ecker JR, Li W, Farnham PJ, Waterland RA, Meissner A, Marra MA, Hirst M, Milosavljevic A, Costello JF.  Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.   Nat Biotechnol. 2010; 28(10):1097-105.

Authors contributed equally

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