N. Luisa Hiller
223 Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Ph.D., Northwestern University Medical School
Postdoctoral Appointment, Center for Genomic Sciences at Allegheny-Singer Research Institute
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.
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 Jun 16;6(3). pii: e00173-15.
Kadam A, Janto B, Eutsey R, Earl JP, Powell E, Dahlgren ME, Hu FZ, Ehrlich GD, Hiller NL. Streptococcus pneumoniae Supragenome Hybridization Arrays for Profiling of Genetic Content and Gene Expression. Curr Protoc Microbiol. 2015 Feb 2;36:9D.4.1-9D.4.20.
Eutsey RA, Hiller NL, Earl JP, Janto BA, Dahlgren ME, Ahmed A, Powell E, Schultz MP, Gilsdorf JR, Zhang L, Smith A, Murphy TF, Sethi S, Shen K, Post JC, Hu FZ, Ehrlich GD. Design and validation of a supragenome array for determination of the genomic content of Haemophilus influenzae isolates. BMC Genomics. 2013 Jul 17;14:484.
Hu FZ, Eutsey R, Ahmed A, Frazao N, Powell E, Hiller NL, Hillman T, Buchinsky FJ, Boissy R, Janto B, Kress-Bennett J, Longwell M, Ezzo S, Post JC, Nesin M, Tomasz A, Ehrlich GD. In vivo capsular switch in Streptococcus pneumoniae--analysis by whole genome sequencing. PLoS One. 2012;7(11):e47983.
Ahmed A, Earl J, Retchless A, Hillier SL, Rabe LK, Cherpes TL, Powell E, Janto B, Eutsey R, Hiller NL, Boissy R, Dahlgren ME, Hall BG, Costerton JW, Post JC, Hu FZ, Ehrlich GD. Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. J Bacteriol. 2012 Aug;194(15):3922-37.
Hiller NL, Eutsey RA, Powell E, Earl J, Janto B, Martin D, Dawid S, Ahmed A, Longwell M, Dahlgren ME, Ezzo S, Tettelin H, Daugherty SC, Mitchell T ,Hillman T,Buchinsky FJ, Tomasz A, de Lencastre H, Sá-Leão R, Post JC, Hu FZ, Ehrlich GD. Differences in Genotype and Virulence among Four Multidrug-Resistant Streptococcus pneumoniae Isolates belonging to the PMEN1 clone. PLoS One 6(12): e28850, 2011.
Hiller NL, Ahmed A, Powell E, Eutsey RA, Earl J, Janto B, Boissy R, Hogg J, Barbadora K, 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 Pathog 6(9): e1001108. doi:10.1371/journal.ppat.1001108, 2010.
Comments in News and Analysis in Nature Reviews Microbiology 9, 230, 2011.
Donati C, Hiller NL, Tettelin H, Muzzi A, Croucher NJ, Angiuoli SV, Oggioni M, Dunning Hotopp JC, Hu FZ, Riley D, 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 Biology11:R107, 2010.
Ehrlich GD, Hiller NL, Hu FZ. What makes pathogens pathogenic. Genome Biol 9; 6:225, 2008
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. J Bacteriol 189; 22: 8186-8195, 2007.
Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estrano C, Haldar K. A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 306; 5703:1934-1937, 2004.
Perspective Article in: Science 306.
Comment in Nature Reviews Microbiology 3, 97-98, 2005.
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 2; 5:e50, 2006.
Comment in Editor's Choice in Science 312; 5780: 1574, 2006.
Haldar K, Kamoun S, Hiller NL, Bhattacharje S, van Ooij C. Common infection strategies of pathogenic eukaryotes. Nat Rev Microbiol 4; 12: 922-931, 2006.
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. J Biol Chem 278; 48: 48413-48421, 2003.