Office Location
3303 Microbial Sciences Building
Education
B.A. – 1989; Saint Olaf College; Northfield, MN
Ph.D. – 1994; Washington University School of Medicine; St. Louis, MO
Postdoctoral Research- Stanford University; Stanford, CA
Laura Knoll graduated from St. Olaf College with a BA in Chemistry and Biology. Her thesis research was in lipid metabolism with Dr. Jeffrey Gordon at Washington University in St. Louis. Laura did her postdoctoral research with Dr. John Boothroyd at Stanford University where she used molecular genetic techniques to study the parasite Toxoplasma gondii. In 2001, she moved to the University of Wisconsin-Madison to join the Medical Microbiology and Immunology Department. When she is not in the lab, Laura likes to play Dungeons and Dragons with her teenage sons.
Selected publications:
2020
Mendoza Cavazos C, Knoll LJ. Entamoeba histolytica: Five facts about modeling a complex human disease in rodents. PLoS Pathog. 2020 Nov 12;16(11):e1008950. doi: 10.1371/journal.ppat.1008950. PMID: 33180884; PMCID: PMC7660559.
Wilson SK, Heckendorn J, Martorelli Di Genova B, Koch LL, Rooney PJ, Morrissette N, Lebrun M, Knoll LJ. A Toxoplasma gondii patatin-like phospholipase contributes to host cell invasion. PLoS Pathog. 2020 Jul 6;16(7):e1008650. doi: 10.1371/journal.ppat.1008650. PMID: 32628723; PMCID: PMC7365478.
Olson WJ, Martorelli Di Genova B, Gallego-Lopez G, Dawson AR, Stevenson D, Amador-Noguez D, Knoll LJ. Dual metabolomic profiling uncovers Toxoplasma manipulation of the host metabolome and the discovery of a novel parasite metabolic capability. PLoS Pathog. 2020 Apr 7;16(4):e1008432. doi: 10.1371/journal.ppat.1008432. PMID: 32255806; PMCID: PMC7164669.
2019
Garfoot AL, Wilson GM, Coon JJ, Knoll LJ. Proteomic and transcriptomic analyses of early and late-chronic Toxoplasma gondii infection shows novel and stage specific transcripts. BMC Genomics. 2019 Nov 14;20(1):859. doi: 10.1186/s12864-019-6213-0. PMID: 31726967; PMCID: PMC6857164.
Arendt M, Elissa J, Schmidt N, Michael E, Potter N, Cook M, Knoll LJ. Investigating the role of interleukin 10 on Eimeria intestinal pathogenesis in broiler chickens. Vet Immunol Immunopathol. 2019 Dec;218:109934. doi: 10.1016/j.vetimm.2019.109934. Epub 2019 Aug 31. PMID: 31520870; PMCID: PMC6861699.
Martorelli Di Genova B, Wilson SK, Dubey JP, Knoll LJ. Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction. PLoS Biol. 2019 Aug 20;17(8):e3000364. doi: 10.1371/journal.pbio.3000364. PMID: 31430281; PMCID: PMC6701743.
Garfoot AL, Cervantes PW, Knoll LJ. Transcriptional Analysis Shows a Robust Host Response to Toxoplasma gondii during Early and Late Chronic Infection in Both Male and Female Mice. Infect Immun. 2019 Apr 23;87(5):e00024-19. doi: 10.1128/IAI.00024-19. PMID: 30858341; PMCID: PMC6479041.
2018
Wilson SK, Knoll LJ. Patatin-like phospholipases in microbial infections with emerging roles in fatty acid metabolism and immune regulation by Apicomplexa. Mol Microbiol. 2018 Jan;107(1):34-46. doi: 10.1111/mmi.13871. Epub 2017 Nov 23. PMID: 29090840; PMCID: PMC5739999.
Knoll LJ, Hogan DA, Leong JM, Heitman J, Condit RC. Pearls collections: What we can learn about infectious disease and cancer. PLoS Pathog. 2018 Mar 29;14(3):e1006915. doi: 10.1371/journal.ppat.1006915. PMID: 29596508; PMCID: PMC5875890.
2016
Milligan-Myhre K, Wilson SK, Knoll LJ. Developmental change in translation initiation alters the localization of a common microbial protein necessary for Toxoplasma chronic infection. Mol Microbiol. 2016 Dec;102(6):1086-1098. doi: 10.1111/mmi.13538. Epub 2016 Oct 14. PMID: 27671212; PMCID: PMC5161674.
Rall G, Knoll LJ. Development of Complex Models to Study Co- and Polymicrobial Infections and Diseases. PLoS Pathog. 2016 Sep 8;12(9):e1005858. doi: 10.1371/journal.ppat.1005858. PMID: 27607188; PMCID: PMC5015861.
Pittman KJ, Cervantes PW, Knoll LJ. Z-DNA Binding Protein Mediates Host Control of Toxoplasma gondii Infection. Infect Immun. 2016 Sep 19;84(10):3063-70. doi: 10.1128/IAI.00511-16. PMID: 27481249; PMCID: PMC5038082.
Knoll LJ. Functional Analysis of the Rhoptry Kinome during Chronic Toxoplasma gondii Infection. mBio. 2016 Jun 14;7(3):e00842-16. doi: 10.1128/mBio.00842-16. PMID: 27302762; PMCID: PMC4916387.
Knoll LJ. Conveying Discovery to a Broad Audience. PLoS Pathog. 2016 May 19;12(5):e1005425. doi: 10.1371/journal.ppat.1005425. PMID: 27196056; PMCID: PMC4873215.
2011-2015
Pittman KJ, Knoll LJ. Long-Term Relationships: the Complicated Interplay between the Host and the Developmental Stages of Toxoplasma gondii during Acute and Chronic Infections. Microbiol Mol Biol Rev. 2015 Dec;79(4):387-401. doi: 10.1128/MMBR.00027-15. PMID: 26335719; PMCID: PMC4557073.
Pittman KJ, Aliota MT, Knoll LJ. Dual transcriptional profiling of mice and Toxoplasma gondii during acute and chronic infection. BMC Genomics. 2014 Sep 20;15(1):806. doi: 10.1186/1471-2164-15-806. PMID: 25240600; PMCID: PMC4177681.
Neal LM, Knoll LJ. Toxoplasma gondii profilin promotes recruitment of Ly6Chi CCR2+ inflammatory monocytes that can confer resistance to bacterial infection. PLoS Pathog. 2014 Jun 12;10(6):e1004203. doi: 10.1371/journal.ppat.1004203. PMID: 24945711; PMCID: PMC4055779.
Tobin Magle C, Pittman KJ, Moser LA, Boldon KM, Knoll LJ. A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis. Infect Immun. 2014 Feb;82(2):618-25. doi: 10.1128/IAI.00444-13. Epub 2013 Nov 25. PMID: 24478077; PMCID: PMC3911373.
Settles EW, Moser LA, Harris TH, Knoll LJ. Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria. Infect Immun. 2014 Mar;82(3):1343-53. doi: 10.1128/IAI.01259-13. Epub 2014 Jan 6. PMID: 24396042; PMCID: PMC3957979.
Payne AJ, Neal LM, Knoll LJ. Fusidic acid is an effective treatment against Toxoplasma gondii and Listeria monocytogenes in vitro, but not in mice. Parasitol Res. 2013 Nov;112(11):3859-63. doi: 10.1007/s00436-013-3574-1. Epub 2013 Aug 16. PMID: 23949312; PMCID: PMC4096717.
Moser LA, Pollard AM, Knoll LJ. A genome-wide siRNA screen to identify host factors necessary for growth of the parasite Toxoplasma gondii. PLoS One. 2013 Jun 28;8(6):e68129. doi: 10.1371/journal.pone.0068129. PMID: 23840822; PMCID: PMC3695992.
Hsiao CH, Luisa Hiller N, Haldar K, Knoll LJ. A HT/PEXEL motif in Toxoplasma dense granule proteins is a signal for protein cleavage but not export into the host cell. Traffic. 2013 May;14(5):519-31. doi: 10.1111/tra.12049. Epub 2013 Feb 26. PMID: 23356236; PMCID: PMC3622808.
Payne TM, Payne AJ, Knoll LJ. A Toxoplasma gondii mutant highlights the importance of translational regulation in the apicoplast during animal infection. Mol Microbiol. 2011 Dec;82(5):1204-16. doi: 10.1111/j.1365-2958.2011.07879.x. Epub 2011 Nov 7. PMID: 22059956; PMCID: PMC4348008.
Tobin CM, Knoll LJ. A patatin-like protein protects Toxoplasma gondii from degradation in a nitric oxide-dependent manner. Infect Immun. 2012 Jan;80(1):55-61. doi: 10.1128/IAI.05543-11. Epub 2011 Oct 17. PMID: 22006568; PMCID: PMC3255658.
Click here for a full list of publications at NCBI’s PubMed
Current Projects
Toxoplasma gondii sexual stage
The Apicomplexan parasite Toxoplasma gondii has a complex life cycle that includes an asexual stage and a sexual stage. In nature, the sexual stage occurs only in cats. Until recently, the reasons for this feline specificity were unknown. Our lab showed that inhibition of the mammalian enzyme delta-6-desaturase (D6D) and consequent elevation of its substrate linoleic acid (LA) can break the species barrier to enable T. gondii sexual development in non-feline hosts.
We are now following up on that finding by asking:
- How does lack of D6D activity enable T. gondii to enter its sexual stage?
- Does build-up of LA create lipid mediators that signal to T. gondii to enter sexual stage?
- What other host/parasite factors are required for T. gondii to undergo sexual reproduction?
- How does T. gondii sense the factors that trigger the switch to the sexual cycle?
We are using mice, mouse-derived organoids, and organoids derived from other species (e.g. cats) in conjunction with genetic, biochemical, and molecular biology tools to answer these questions.
Developing models for Entamoeba histolytica infection
Entamoeba histolytica is another single-celled eukaryotic intestinal parasite that causes diarrhea. E. histolytica is a challenging organism to work with in the laboratory, but the Knoll Lab recently developed a reliable animal model for an oral route of E. histolytica infection. We are further developing this model by characterizing pathology and parasite load in the intestine, and by building additional in vivo and in vitro tools to model invasive disease. Future work will enable us to identify host, parasite, and environmental factors that affect E. histolytica infection.
Understanding diseases caused by Cryptosporidium parvum infection
Cryptosporidium parvum is an Apicomplexan parasite that causes non-bloody diarrhea. It is also associated with colorectal cancer in humans and causes cancer in some mouse models. To understand how C. parvum causes acute intestinal disease and cancer, we are using RNA-seq and metabolomics to identify host and parasite factors that differentiate healthy from diseased states. Future efforts will determine the mechanisms by which these factors cause or limit C. parvum-induced disease.
Host factors in parasitic infections
Numerous host genes affect the outcomes of parasitic infection. We are interested in host immune genes that affect infection outcomes by modulating interferon responses (e.g. IFN-γ, ZBP1) and necroptosis (ZBP1, RIPK3). To understand how these genes alter parasite and/or host biology during infection, we first identify candidate molecular mechanisms by comparing parasite-infected knockout mice to their wildtype controls. We then use biochemical, molecular biology, and immunological tools to further dissect how these mechanisms work.
Ongoing Interests
Multi-omics
Recent advances in “omics” technologies enabled widespread collection of transcriptomic, proteomic, and metabolomic data that reveal the regulatory and biochemical landscapes of biological systems. Our lab has employed multi-omics to understand different facets of parasite biology, especially in T. gondii. Examples include discovery of host sex-specific differences in infection dynamics, identification of factors that differentiate acute and chronic infection, and new insights into microbial metabolism.
Microbial metabolism
Parasites rely on their hosts to obtain nutrients, so it is not surprising that metabolic genes are often critical for parasites to grow, replicate, and disseminate throughout a host. Parasite metabolism can also alter host physiology and manipulate immune responses. We are interested in understanding the mechanisms by which parasite metabolism genes enable colonization and affect the host.
Chronic infection
Toxoplasma gondii is an immensely successful parasite in the sense that once it colonize a host, the host is infected for life. T. gondii persists in the host tissues in cyst form, a unique lifestyle that requires many parasite adaptations. We want to determine which parasite and host genes enable persistent T. gondii infection and how those genes work.
Awards
- 2024, UW-Madison Kellett Mid-Career Award
- 2012, UW-Madison WARF Romnes Faculty Fellow
- 2009, Biomedical Research Award from the Hartwell Foundation
- 2008, Established Investigator Award from the American Heart Association
- 2007, Research Scholar Award from the American Cancer Society
- 2003, Shaw Scientist Award, funded by the Greater Milwaukee Foundation
- 2000, Burroughs Wellcome Career Award