N. Luisa Hiller
Eberly Family Career Development Associate Professor of Biological Sciences
Address:
223 Mellon Institute
Department of Biological Sciences
Ò»±¾µÀÎÞÂë
4400 Fifth Avenue
Pittsburgh, PA 15213
Phone: 412-268-2081
Fax: 412-268-7129
Education
Ph.D., Northwestern University Medical School
Postdoctoral Appointment, Center for Genomic Sciences at Allegheny-Singer Research Institute
Research
Billions of bacteria colonize the healthy human body. Conversely, bacterial infections are among the leading causes of human morbidity and mortality. My laboratory is interested in understanding the role of bacteria in both health and disease. Our current focus is on the commensal pathogen Streptococcus pneumoniae, an organism with enormous genotypic/phenotypic variations among pneumococcal strains, as well as a high degree of genomic plasticity.
To study and better understand this genomic diversity and plasticity in the context of both isolated infections and in epidemics, my laboratory applies techniques of comparative genomics, bioinformatics, and phylogenetics to banked bacterial isolates from clinical infections. Furthermore, the integration of comparative genomics and clinical phenotype provides a rich source of data from which to generate hypotheses on gene function and mechanism, which we verify using molecular and cellular biology techniques in the laboratory.
My laboratory is investigating the following critical questions: (1) if and how the distributions of bacterial strains present in carriage differ from those in infections, (2) how related these different strains are from one another, (3) in what time frame and to what extent do strains modify their genetic compositions, (4) what factors affect their genomic plasticity and, (5) what molecules facilitate intra- and inter-species communications and host interactions.
Publications
Mueller Brown K, Eutsey R, Gazioglu O, Wang D, Vallon A, Rosch JW, Yesilkaya H, Hiller NL. Peptide maturation molecules act as molecular gatekeepers to coordinate cell-cell communication in Streptococcus pneumoniae. Cell Rep. 2024 Jul 23;43(7):114432. doi: 10.1016/j.celrep.2024.114432. Epub 2024 Jul 3. PubMed PMID: 38963762; PubMed Central PMCID: PMC11323143
Abdullah IT, Ulijasz AT, Girija UV, Tam S, Andrew P, Hiller NL, Wallis R, Yesilkaya H. Structure-function analysis for the development of peptide inhibitors for a Gram-positive quorum sensing system. Mol Microbiol. 2022 Jun;117(6):1464-1478. doi: 10.1111/mmi.14921. Epub 2022 May 28. PubMed PMID: 35575437; PubMed Central PMCID: PMC9233744
Yerneni SS, Werner S, Azambuja JH, Ludwig N, Eutsey R, Aggarwal SD, Lucas PC, Bailey N, Whiteside TL, Campbell PG, Hiller NL. Pneumococcal Extracellular Vesicles Modulate Host Immunity. mBio. 2021 Jul 13:e0165721. doi: 10.1128/mBio.01657-21. Epub ahead of print. PMID: 34253061
Aggarwal SD, Gullett JM, Fedder T, Safi JPF, Rock CO, Hiller NL. Competence-Associated Peptide BriC Alters Fatty Acid Biosynthesis in Streptococcus pneumoniae. mSphere. 2021 Jun 30;6(3):e0014521. doi: 10.1128/mSphere.00145-21. Epub 2021 May 26. PMID: 34192504
Aggarwal SD, Lloyd AJ, Yerneni SS, Narciso AR, Shepherd J, Roper DI, Dowson CG, Filipe SR, Hiller NL. A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae. Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e2018089118
Aggarwal SD, Yesilkaya H, Dawid SR, Hiller NL. The Pneumococcal Social Network. PLoS Pathogens 16 (10), Oct 2020
Mueller-Brown K, Le Sage V, French AJ, Jones JE, Padovani GH, Avery AJ, Hiller NL*, Lakdawala SS*. Coinfection of Streptococcus pneumoniae reduces airborne transmission of influenza virus. *co-corresponding authors. bioRxiv 2020.11.10.376442
Aggarwal SD, Eutsey R, West-Roberts J, Domenech A, Xu W, Abdullah IT, Mitchell AP, Veening JW, Yesilkaya H, Hiller NL. Function of BriC peptide in the pneumococcal competence and virulence portfolio. PLoS Pathog. 2018 Oct 11;14(10):e1007328. doi: 10.1371/journal.ppat.1007328. eCollection 2018 Oct. PMID: 30308062
Davidson P, Eutsey R, Redler B, Hiller NL, Laub MT, Durand D. Flexibility and constraint: Evolutionary remodeling of the sporulation initiation pathway in Firmicutes. PLoS Genet. 2018 Sep 13;14(9):e1007470. doi: 10.1371/journal.pgen.1007470. eCollection 2018 Sep. PMID: 30212463
Motib A, Guerreiro A, Al-Bayati F, Piletska E, Manzoor I, Shafeeq S, Kadam A, Kuipers O, Hiller L, Cowen T, Piletsky S, Andrew P, Yesilkaya H. Modulation of Quorum Sensing in a Gram Positive Pathogen by Linear Imprinted Copolymers with anti-Infective Properties. Angew Chem Int Ed Engl. 2017 Nov 15. doi: 10.1002/anie.201709313 PMID: 29140595
Antic I, Brothers KM, Stolzer M, Lai H, Powell E, Eutsey R, Cuevas RA, Miao X, Kowalski RP, Shanks RMQ, Durand D, Hiller NL. Gene Acquisition by a Distinct Phyletic Group within Streptococcus pneumoniae Promotes Adhesion to the Ocular Epithelium. mSphere. 2017 Oct 25;2(5). pii: e00213-17. doi: 10.1128/mSphere.00213-17. eCollection 2017 Sep-Oct. PMID: 29085912
Cuevas RA, Eutsey R, Kadam A, West-Roberts JA, Woolford CA, Mitchell AP, Mason KM, Hiller NL. A novel streptococcal cell-cell communication peptide promotes pneumococcal virulence and biofilm formation. Mol Microbiol. 2017 May 29. doi: 10.1111/mmi.13721. PMID: 28557053
Kadam A, Eutsey RA, Rosch J, Miao X, Longwell M, Xu W, Woolford CA, Hillman T, Motib AS, Yesilkaya H, Mitchell AP, Hiller NL. Promiscuous signaling by a regulatory system unique to the pandemic PMEN1 pneumococcal lineage. PLoS Pathog. 2017 May 18;13(5):e1006339. doi: 10.1371/journal.ppat.1006339. eCollection 2017 May. PMID: 28542565
Eutsey RA, Powell E, Dordel J, Salter SJ, Clark TA, Korlach J, Ehrlich GD, Hiller NL. Genetic Stabilization of the Drug-Resistant PMEN1 Pneumococcus Lineage by Its Distinctive DpnIII Restriction-Modification System. mBio. 2015; 6(3):e00173.PubMed [journal] PMID: 26081630, PMCID: PMC4471560
Hiller NL, Ahmed A, Powell E, Martin DP, Eutsey R, Earl J, Janto B, Boissy RJ, Hogg J, Barbadora K, Sampath R, Lonergan S, Post JC, Hu FZ, Ehrlich GD. Generation of genic diversity among Streptococcus pneumoniae strains via horizontal gene transfer during a chronic polyclonal pediatric infection. PLoS pathogens. 2010; 6(9):e1001108. PubMed [journal] PMID: 20862314, PMCID: PMC2940740
Donati C, Hiller NL, Tettelin H, Muzzi A, Croucher NJ, Angiuoli SV, Oggioni M, Dunning Hotopp JC, Hu FZ, Riley DR, Covacci A, Mitchell TJ, Bentley SD, Kilian M, Ehrlich GD, Rappuoli R, Moxon ER, Masignani V. Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species. Genome biology. 2010; 11(10):R107. PubMed [journal] PMID: 21034474, PMCID: PMC3218663
Ehrlich GD, Hiller NL, Hu FZ. What makes pathogens pathogenic. Genome biology. 2008; 9(6):225. PubMed [journal] PMID: 18598378, PMCID: PMC2481411
Hiller NL, Janto B, Hogg JS, Boissy R, Yu S, Powell E, Keefe R, Ehrlich NE, Shen K, Hayes J, Barbadora K, Klimke W, Dernovoy D, Tatusova T, Parkhill J, Bentley SD, Post JC, Ehrlich GD, Hu FZ. Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: insights into the pneumococcal supragenome. Journal of bacteriology. 2007; 189(22):8186-95. PubMed [journal] PMID: 17675389, PMCID: PMC2168654
Bhattacharjee S, Hiller NL, Liolios K, Win J, Kanneganti TD, Young C, Kamoun S, Haldar K. The malarial host-targeting signal is conserved in the Irish potato famine pathogen. PLoS pathogens. 2006; 2(5):e50. PubMed [journal] PMID: 16733545, PMCID: PMC1464399
Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estraño C, Haldar K. A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science (New York, N.Y.). 2004; 306(5703):1934-7. PubMed [journal] PMID: 15591203
Hiller NL, Akompong T, Morrow JS, Holder AA, Haldar K. Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites. A role for microbial raft proteins in apicomplexan vacuole biogenesis. The Journal of biological chemistry. 2003; 278(48):48413-21. PubMed [journal