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Julie C. Dunning Hotopp, PhD

Academic Title:

Associate Professor

Primary Appointment:

Microbiology and Immunology

Additional Title:

Associate Professor, Institute for Genome Science

Location:

BioPark II, 631

Phone (Primary):

(410) 706-5673

Fax:

(410) 706-1482

Education and Training

  • 1993-1997: B.S., magna cum laude, Microbiology and Immunology, Univeristy of Rochester, Rochester, NY
  • 1997-2002: Ph.D., Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI. Mentor: Dr. Robert Hausinger
  • 2002-2005: Postdoctoral Fellow, The Institute for Genomic Research, Rockville, MD. Mentor: Dr. Hervé Tettelin

Biosketch

Our most significant scientific contribution relates to our ground breaking work documenting extensive lateral gene transfer between symbionts and invertebrates (Dunning Hotopp et al. 2007 Science 317: 1753-1756). This paradigm-shifting discovery was highlighted in numerous news articles for both the science community and the general public. This includes a 73rd place ranking by Discover Magazine in its listing of the top 100 discoveries of 2007. Following this discover in invertebrates, we sought to understand if bacterial DNA can also integrate into vertebrate somatic genomes, most notably the human somatic genome. In 2013, we presented computational evidence that such integrations occur in humans and can be detected in cancer genomes.  Currently our group is focusing on validating these results and extending the analysis to more cancer types. In addition to our research emphasis on bacteria-animal lateral gene transfer, we also focus on the the genomics of numerous pathogens and their hosts, including Wolbachia of insects and nematodes, Ehrlichia, Anaplasma, and Neisseria.

Research/Clinical Keywords

lateral gene transfer, horizontal gene transfer, genomics, human somatic genome, Wolbachia, Drosophila ananassae, filarial nematodes, Neisseria meningitidis, Ehrlichia, Anaplasma, Rickettisales, Anaplasmataceae

Highlighted Publications

Dunning Hotopp, J. C., M. E. Clark, D. C. S. G. Oliveira, J. M. Foster, P. Fischer, M. C. Muñoz Torres, J. D. Giebel, N. Kumar, N. Ishmael, S. Wang, J. Ingram, R. V. Nene, J. Shepard, J. Tomkins, S. Richards, D. J. Spiro, E. Ghedin, B. E. Slatko, H. Tettelin, and  J. H. Werren. (2007) “Widespread Lateral Gene Transfer from Intracellular Bacteria to Multicellular Eukaryotes.” Science 317(5845):1753-6.

Riley, D. R., K. B. Sieber, K. M. Robinson, J. R. White, A. Ganesan, S. Nourbakhsh, and J. C. Dunning Hotopp. 2013. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS Comput Bio, 9(6): e1003107.

Ioannidis, P, K. L. Johnston, D. R. Riley, N. Kumar, J. R. White, K. T. Olarte, S. Ott, L. J. Tallon, J. M. Foster, M. J. Taylor, and J. C. Dunning Hotopp. (2013) “Extensively duplicated and transcriptionally active recent lateral gene transfer from a bacterial Wolbachia endosymbiont to its host filarial nematode Brugia malayi.” BMC Genomics 14:639.

Tallon, L. J., X. Liu, S. Bennuru, M. C. Chibucos, A. Godinez, S. Ott, X. Zhao, L. Sadzewicz, C. M. Fraser, T. B. Nutman, and J. C. Dunning Hotopp. (2014.) “Single molecule sequencing and genome assembly of a clinical specimen of Loa loa, the causative agent of loiasis.” BMC Genomics 15:788.

Klasson, L., N. Kumar, R. Bromley, K. Sieber, M. Flowers, S. H. Ott, L. J. Tallon, S. G. Andersson, and J. C. Dunning Hotopp. (2014) “Extensive duplication of the Wolbachia DNA in chromosome four of Drosophila ananassae.” BMC Genomics 15:1097.

Additional Publication Citations

Dunning Hotopp, J. C., M. Lin, R. Madupu, J. Crabtree, S. V. Angiuoli, J. Eisen, R. Seshadri, Q. Ren, M. Wu, T. R. Utterback, S. Smith, M. Lewis, H. Khouri, C. Zhang, N. Hua, Q. Lin, N. Ohashi, N. Zhi, W. Nelson, L. M. Brinkac, R. J. Dodson, M. J. Rosovitz, J. Sundaram, S. C. Daugherty, T. Davidsen, A. Durkin, M. Gwinn, D. H. Haft, J. D. Selengut, S. A. Sullivan, N. Zafar, L. Zhou, F. Benahmed, H. Forberger, R. Halpin, S. Mulligan, J. Robinson, Y. Rikihisa, and H. Tettelin. (2006) “Comparative Genomics of Emerging Human Ehrlichiosis Agents.” PLoS Genet. 2(2):e21.

Dunning Hotopp, J. C., R. Grifantini, N. Kumar, Y. L. Tzeng, D. Fouts, E. Frigimelica, M. Draghi, M. M. Giuliani, R. Rappuoli, D. S. Stephens, G. Grandi, and H. Tettelin. (2006) “Comparative Genomics of Neisseria meningitidis: Core Genome, Islands of Horizontal Transfer and Pathogen Specific Genes.” Microbiology 152(12):3733-49.

Dunning Hotopp, J. C., M. E. Clark, D. C. S. G. Oliveira, J. M. Foster, P. Fischer, M. C. Muñoz Torres, J. D. Giebel, N. Kumar, N. Ishmael, S. Wang, J. Ingram, R. V. Nene, J. Shepard, J. Tomkins, S. Richards, D. J. Spiro, E. Ghedin, B. E. Slatko, H. Tettelin, and  J. H. Werren. (2007) “Widespread Lateral Gene Transfer from Intracellular Bacteria to Multicellular Eukaryotes.” Science 317(5845):1753-6.

Bordenstein, S.R., C. Paraskevopoulos, J. C. Dunning Hotopp, P. Sapountzis, N. Lo, C. Bandi, H. Tettelin, J. Werren, and K. Bourtzis. (2009) “Parasitism and mutualism in Wolbachia: what the phylogenomic trees can and cannot say,” Mol Biol Evol 26(1):231-41.

Ishmael, N., J. C. Dunning Hotopp, P. Ioannidis, S. Biber, J. Sakamoto, S. Siozios, V. Nene, J. H. Werren, K. Bourtzis, S. R. Bordenstein, and H. Tettelin. (2009). “Extensive genomic diversity of closely related Wolbachia strains.” Microbiology 155:2211-2222.

McNulty, S. N., J. Foster, M. Mitreva, J. C. Dunning Hotopp, J. Martin, K. Fischer, B. Wu, P. J. David, S. Kumar, N. W. Brattig, B. E. Slatko, G. J. Weil, and P. U. Fischer. (2010) “Endosymbiont DNA in endobacteria-free filarial nematodes indicates past symbiosis and ancient horizontal genetic transfer.” PLoS ONE 5(6): e11029.

Donati, C., N. L. Hiller, H. Tettelin, A. Muzzi, N. J. Croucher, S. V. Angiuoli, M. Oggioni, J. C. Dunning Hotopp, F. Z. Hu, D. R. Riley, A. Covacci, T. J. Mitchell, S. D. Bentley, M. Kilian, G. D. Ehrlich, R. Rappuoli, E. R. Moxon, and V. Masignani. (2010) “Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species.” Genome Biol. 11:R107.

Budroni, S., E. Siena, J. C. Dunning Hotopp, K. Sieb, D. Serruto, C. Nofroni, M. Comanducci, D. Riley, S. Daugherty, S. Angiuoli, A. Covacci, M. G. Pizza, R. Rappuoli, R. Moxon, H. Tettelin, and D. Medini. (2011) “Neisseria meningitidis population is structure in phylogenetic clades, associated with restriction-modification systems that modulate the effect of homologous recombination.” Proc Natl Acad Sci U S A 108(11):4494-9.

Dunning Hotopp, J. C. (2011) “Horizontal Gene Transfer Between Bacteria and Animals” Trends in Genetics, 27(4):157-63.

Angiuoli, S. V., J. C. Dunning Hotopp, S. L. Salzberg, and H. Tettelin. (2011) “Improving pan-genome annotation using whole genome multiple alignment.” BMC Bioinformatics, 12:272.

Riley D. R., S. V. Angiuoli, J. Crabtree, J. C. Dunning Hotopp, and H. Tettelin. (2012) “Using Sybil for interactive comparative genomics of microbes on the web.” Bioinformatics 28(2):160-6.

Krauland, M. G., J. C. Dunning Hotopp, D. R. Riley, S. C. Daugherty, J. W. Marsh, N. E. Messonnier, L. W. Mayer, H. Tettelin, and L. H. Harrison. (2012) “Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States.” PLoS One 7(4):e35699.

Kumar, N., T. Creasy, Y. Sun, M. Flowers, L. J. Tallon, and J. C. Dunning Hotopp. (2012) “Efficient subtraction of insect rRNA prior to transcriptome analysis of Wolbachia-Drosophila lateral gene transfer.” BMC Res Note 5(1):230.

Desjardins, C. A., G. C. Cerqueira, J. M. Goldberg, J. C. Dunning Hotopp, B. J. Haas, J. Zucker, J. M. Ribeiro, S. Saif, J. Z. Levin, L. Fan, Q. Zeng, C. Russ, J. R. Wortman, D. L. Fink, B. W. Birren, T. B. Nutman. (2013) “Genomics of Loa loa, a Wolbachia-free filarial parasite of humans.” Nat Genet 45(5):495-500.

Riley, D. R., K. B. Sieber, K. M. Robinson, J. R. White, A. Ganesan, S. Nourbakhsh, and J. C. Dunning Hotopp. 2013. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS Comput Bio, 9(6): e1003107.

Ioannidis, P, K. L. Johnston, D. R. Riley, N. Kumar, J. R. White, K. T. Olarte, S. Ott, L. J. Tallon, J. M. Foster, M. J. Taylor, and J. C. Dunning Hotopp. (2013) “Extensively duplicated and transcriptionally active recent lateral gene transfer from a bacterial Wolbachia endosymbiont to its host filarial nematode Brugia malayi.” BMC Genomics 14:639.

Estes, A. M., D. J. Hearn, E. C. Snell-Rood, M. Feindler, K. Feeser, T. Abebe, J. C. Dunning Hotopp and Armin P. Moczek. (2013) “Brood ball-mediated transmission of microbiome members in the dung beetle, Onthophagus taurus (Coleoptera: Scarabaeidae).” PLoSOne 8(11):e79061.

Robinson, K. M., K. B. Sieber, and J. C. Dunning Hotopp. (2013) “A review of bacteria-animal lateral gene transfer may inform our understanding of diseases like cancer” PLoS Genetics 9(10):e1003877.

Dugan V. G. , S. J. Emrich, G. I. Giraldo-Calderón, O. S. Harb, R. M. Newman, B. E. Pickett, L. M. Schriml, T. B. Stockwell, C. J. Stoeckert, D. E. Sullivan, I. Singh, D. V. Ward, A. Yao, J. Zheng, T. Barrett, B. Birren, L. Brinkac, V. M. Bruno, E. Caler, S. Chapman, F. H. Collins, C. A. Cuomo, V. Di Francesco, S. Durkin, M. Eppinger, M. Feldgarden, C. Fraser, W. F. Fricke, M. Giovanni, M. R. Henn, E. Hine, J. Dunning Hotopp, I. Karsch-Mizrachi, J. C. Kissinger, E. M. Lee, P. Mathur, E. F. Mongodin, C. I. Murphy, G. Myers, D. E. Neafsey, K. E. Nelson, W. C. Nierman, J. Puzak, D. Rasko, D. S. Roos, L. Sadzewicz, J. C. Silva, B. Sobral, R. B. Squires, R. L. Stevens, L. Tallon, H. Tettelin, D. Wentworth, O. White, R. Will, J. Wortman, Y. Zhang, R. H. Scheuermann. (2014) “Standardized Metadata for Human Pathogen/Vector Genomic Sequences.” PLoSOne 9(6):e99979.

Tallon, L. J., X. Liu, S. Bennuru, M. C. Chibucos, A. Godinez, S. Ott, X. Zhao, L. Sadzewicz, C. M. Fraser, T. B. Nutman, and J. C. Dunning Hotopp. (2014.) “Single molecule sequencing and genome assembly of a clinical specimen of Loa loa, the causative agent of loiasis.” BMC Genomics 15:788.

Ioannidis, P., Y. Lu, N. Kumar, T. Creasy, S. Daugherty, M. C. Chibucos, J. Orvis, A. Shetty, S. Ott, M. Flowers, N. Sengamalay, L. J. Tallon, L. Pick and J. C. Dunning Hotopp. (2014) “Rapid transcriptome sequencing of an invasive pest, the brown marmorated stink bug Halyomorpha halys.” BMC Genomics 15:738.

Klasson, L., N. Kumar, R. Bromley, K. Sieber, M. Flowers, S. H. Ott, L. J. Tallon, S. G. Andersson, and J. C. Dunning Hotopp. (2014) “Extensive duplication of the Wolbachia DNA in chromosome four of Drosophila ananassae.” BMC Genomics 15:1097.

Robinson, K. M., and J. C. Dunning Hotopp. (2014) “Mobile elements and viral integrations prompt considerations for bacterial DNA integration as a novel carcinogen.” Cancer Lett 352:137-44.

Dunning Hotopp, J. C., A. M. Estes (2014) “Biology wars: the eukaryotes strike back.” Cell Host Microbe 16:701-3.

Mustapha, M. M., J. W. Marsh, M. G. Krauland, J. O. Fernandez, A. P. de Lemos, J. C. Dunning Hotopp, X. Wang, L. W. Mayer, J. G. Lawrence, N. L. Hiller, L. H. Harrison (2015) “Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis.” EBioMedicine 2(10):1447-55.

Sieber, K. B., P. Gajer, and J. C. Dunning Hotopp. (2016) “Modeling the integration of bacterial rRNA fragments into the human cancer genome.” BMC Bioinformatics 17:134.

Mustapha, M. M., J. W. Marsh, M. G. Krauland, J. O. Fernandez, A. P. de Lemos, J. C. Dunning Hotopp, X. Wang, L. W. Mayer, J. G. Lawrence, N. L. Hiller, L. H. Harrison (2016) “Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains,” Genome Biol Evol 8(6):2065-75.

Kumar N., M. Lin, X. Zhao, S. Ott, I. Santana-Cruz, S. Daugherty, Y. Rikihisa, L. Sadzewicz, L. J. Tallon, C. M. Fraser, J. C. Dunning Hotopp (2016) “Efficient Enrichment of Bacterial mRNA from Host-Bacteria Total RNA Samples,” Sci Rep 6:34850.

 

Research Interests

Lateral Gene Transfer in Drosophila ananassae

Our goal is to elucidate the genomic changes resulting from LGT from Wolbachia bacteria to their animal hosts. In the fruit flyDrosophila ananassae, an entire Wolbachia genome has inserted into the host 2L chromosome. We have sequenced both the insert and the endosymbiont genome and have analyzed them using comparative genomic and molecular population genetic techniques to determine the mutational pressures acting on bacterial DNA in a eukaryotic genome.

Lateral Gene Transfer in Filarial Nematodes

Approximately 120 million people worldwide have lymphatic filariasis and another 1.2 billion people, predominantly in the developing world, are at risk of infection in 83 countries and territories in Asia, Africa, the Pacific, and the Americas. Although rarely fatal, the disease causes significant pain, profound disfigurement, and substantial stigma. Our goal is to identify and target bacterial genes transferred to filarial nematodes chromosomes that may provide novel drug targets in the treatment of lymphatic filariasis and the related river blindness.

Lateral Gene Transfer in the Human Somatic Genome

Approximately 90% of the cells in the human body are commensal and pathogenic bacteria. Thus, our mucosal cells are bathed in bacterial DNA. The American Cancer Society estimates that 10% of cancers in developed countries are linked to infections, although many of the mechanisms are unknown. We hypothesize that bacterial DNA incorporates into the chromosomes of our somatic cells. Such integrations can lead to gene disruptions in somatic cells analogous to disease causing mutations resulting from insertion of retroviruses, transposons, or mitochondrial DNA.

Genomics of Neisseria meningitidis

Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia globally and can lead to death or serious, permanent and disabling sequelae. Meningococcal disease incidence is cyclical, with peaks and troughs of incidence.The primary objective of this study is to identify genetic factors associated with the emergence of endemic and epidemic meningococcal disease worldwide. Long term, this research project is designed to improve our understanding of meningococcal disease dynamics and provide a basis for development of a cost-effective universal vaccine that could be used globally.

Genomics of Human Ehrlichiosis Agents

Ehrlichia chaffeensis is the etiologic agent of human monocytic ehrlichiosis (HME), one of the most prevalent, life-threatening emerging tick-borne zoonoses in the United States. By correlating the genome sequences and the transcriptome profiles of E. chaffeensis strains with the diverse disease phenotypes of these strains, we will identify the virulence determinants responsible for particular disease manifestations, disease severity, and bacterial pathogenesis.

Awards and Affiliations

  • 2010                NIH Director’s New Innovator Award, NIH
  • 2010                Leading Women of Maryland, Maryland Daily Record
  • 2010                Genome Technology Young Investigator, Genome Technology

Links of Interest

http://www.igs.umaryland.edu/labs/lgthgt/

http://www.igs.umaryland.edu/labs/hotopp/

https://www.youtube.com/channel/UC7xumz0lLSolW8XKIHNJ-GQ