Monique Van Hoek, Ph.D., Associate Professor

Biosketch

Dr. Van Hoek received her bachelors degree in Biochemistry from the University of Victoria (Canada). She received her PhD from the University of Virginia, Department of Microbiology working in the Parsons-Weber-Parsons group. Dr. van Hoek then worked for Boehringer-Mannheim, which then became Roche Molecular Biochemical Division, for many years, developing and launching new biochemical products for life-science researchers.  She joined George Mason University in 2002.  Dr. van Hoek conducts her research in the School of Systems Biology and the National Center for Biodefense and Infectious Diseases with a focus on tularemia, novel antimicroibals and host-pathogen interactions.  Dr. van Hoek currently teaches BIOL 404: Medical Microbiology and BIOL 506: Cellular Microbiology.

Contact InformationEmail  mvanhoek@gmu.edu Phone: 703.993.4273 Fax: 703.993.7019

Talks::

TEDxGeorgeMasonU talk: “Healed by a Crocodile: the Search for New Antibiotics”. April 6th 2013

Expert Commentary:

Expert Commentary: Chemistry World: Could wasp venom peptide keep catheters sterile? 14 August 2013

Research Interests

Drug delivery and treatment for Francisella tularensis (tularemia), other gram-negative and gram-positive human pathogens (Pseudomonas, Staphylococcus aureus (MRSA), Acinetobacter, Mycobacterium), Host-Pathogen Interactions (especially phosphorylation-based signal transduction), Development of novel antimicrobials and anti-biofilm compounds, Microbial physiology of Francisella, Bacterial vaccines, Outer Membrane Vesicles, Proteomics, Bacterial biofilms and quorum sensing, exosomes.

Research Program

The van Hoek lab is currently pursuing research projects exploring novel antimicrobials, bacterial physiology and pathogenesis of Francisella tularensis in the mammalian host.  We are particularly interested in developing new classes of antimicrobial agents for this and other gram-negative pathogens to combat antimicrobial resistance. In addition, we are developing anti-biofilm compounds.  Techniques of cell biology, biochemistry, microbiology and proteomics are used to address questions of how Francisella infects its host, and what factors cause it to be virulent. Dr. van Hoek has graduate students from the Biodefense, Bioscience and Biology graduate programs. Current projects involve nano-aerosol drug delivery using an aerosol model of Francisella infection, proteomic, microarray and bioinformatic analysis of host-pathogen interactions and studies of microbial physiology.

Nano-aerosol for antimicrobial drug delivery to pneumonic tularemia. Francisella (F.) tularensis is an important pathogen endemic to Russia, and a Category A Select Agent in the USA. Recently, the technology of nano-aerosols has been developed. Drug delivery by this route reduced the required dose of inhaled drugs by 3-6 orders of magnitude compared to the oral route. The objective of this research is to develop a device to generate nano-aerosols of drugs to treat tularemia infection of the lung, taking advantage of all of the benefits of inhalational therapeutics (reduced systemic exposure, highly local concentration of drug delivery) plus the benefits of nano-aerosol (deep penetration, enhanced deposition and tremendous reduction in required dose). This is a novel approach to treatment of tularemia. In the long-term, nano-aerosol drug delivery could change how inhaled therapeutics are used in medicine. This project contributes to the C-WMD needs by combining the expertise and experience of the Russian team, headed by Dr. Victor Morozov, Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences, in the generation of biologically active nano-aerosols with the expertise of US team, headed by Dr. M. van Hoek, GMU, in the study of Francisella and BSL-3 laboratory capabilities, promoting cooperative science and advancing fundamental research into therapeutics for tularemia. This fundamental research is directed towards the development of new therapeutics for endemic pathogens within Russia.

Host-Pathogen Interactions. Facultative intracellular pathogens such as Francisella must interact intimately with the host to induce their uptake into macrophages and other cell types as part of the infectious process.  Investigating the result of this interaction based on phospho-proteomic analysis of infected cells, through reverse phase protein microarrays (RPMA) demonstrated that many critical host-cell signaling pathways are perturbed by Francisella infection.  These include alteration in MapK/p38, Akt and other molecules consistent with activation of the TLR pathway.  Microarray analysis of Francisella infected lung cells indicated that several biochemical pathways were consistently over-represented, including those related to cytoskeletal organization and macropinocytosis.  The alteration in gene expression of these genes could indicate a role for these cellular-processes in Francisella infection of host cells, which we are currently exploring.  Ongoing research is focused on characterizing the mechanism of Francisella uptake into lung cells in order to identify novel vaccine or therapeutic targets.

Microbial Physiology of Francisella and Vaccine development. Despite intensified study in the last decade, our understanding of the microbial physiology of Francisella still greatly lags behind more well-known bacteria such as E. coli.  Indeed, this organism presents many unique challenges to the microbiologist for study.  In our research, we have demonstrated that Francisella species form biofilms in vitro.  We are currently studying the mechanism by which this process is regulated. We have identified that Francisella species produce Outer Membrane Vesicles, and have studied the mechanism by which this occurs.  We have also shown that these vesicles contribute to Francisella biofilm formation.  Perhaps most importantly, we have demonstrated that these vesicles can be used as an effective vaccine for Francisella.  This study confirms the importance of studying fundamental microbial physiology, as it leads to new understanding of the organism that can then lead to new treatments or in this case, a vaccine.

Novel Antimicrobial and Antibiofilm compounds. There is a critical need for new antimicrobial drugs, especially against gram-negative pathogens.  Many pathogens are now multi-drug resistant, with few options for treatment. In collaboration with Dr. Barney Bishop, GMU, we have been studying antimicrobial peptides.  These naturally produced peptides provide “pre-validated” (by evolutionary selection) templates for the design of new classes of antimicrobial agents.  We are also focused on the problem of bacterial biofilms, pursuing the hypothesis that disrupting the bacterial biofilm could be a useful approach to treating a bacterial infection. In collaboration with Dr. Robin Couch, GMU, we have been studying inhibitors of the MEP pathway, including fosmidomycin, as a platform from which to develop other new antimicrobials.

Pathophysiology of the human lung. As a result of our interest in aerosolized and inhaled bacterial threat agents, we have become very interested in the “host” side of this equation, the human lung.   In particular, we are interested in understanding the role of innate immunity in the lung, particularly the alveolus, especially with respect to antimicrobial peptides.  We have shown that bacterial infection of lung cells by Francisella induces certain antimicrobial peptide expression, but not the peptides that are most effective against this organism.  Recent work suggested a role for alpha-defensin antimicrobial peptide expression in the lung disease idiopathic pulmonary fibrosis (IPF).  In collaboration with Dr. Steven Nathan and Dr. Shahzad Ahmed at INOVA Fairfax Hospital, and Dr. Geraldine Grant at GMU, we are studying the expression of some of the 33 newly identified human beta-defensin genes in normal and IPF human lung.

Selected Publications

 

van Hoek ML.  Antimicrobial Peptides in Reptiles. Pharmaceuticals (Basel). 2014 Jun 10;7(6):723-753. Chung MC, Dean S, Marakasova ES, Nwabueze AO, van Hoek ML. Chitinases are negative regulators of Francisella novicida biofilms. PLoS One. 2014 Mar 24;9(3):e93119.

Fleming A, Sampey G, Chung MC, Bailey C, van Hoek ML, Kashanchi F, Hakami RM. The carrying pigeons of the cell: exosomes and their role in infectious diseases caused by human pathogens. Pathog Dis. 2014 Jan 21.

van Hoek ML. Biofilms: an advancement in our understanding of Francisella species. Virulence. 2013 Nov 15;4(8):833-46.

Duplantier AJ, van Hoek ML. The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds. Front Immunol. 2013 Jul 3;4:143.

Pierson T, Learmonth-Pierson S, Pinto D, van Hoek ML. Cigarette smoke extract induces differential expression levels of beta-defensin peptides in human alveolar epithelial cells. Tob Induc Dis. 2013 Apr 29;11(1):10.

Han, S., Bishop, B.M., M.L. van Hoek. Antimicrobial activity of human beta-defensins and induction by Francisella. (2008) Biochem Biophys Res Commun. 371(4): 670-4.

Papanastasiou, E. A., Hua Q., Sandouk A., Son U., Christenson A.J., M.L. van Hoek and B.M. Bishop.  Acetylation, Charge and Antimicrobial Potency in Small Cationic Peptides Based on Human Beta-defensin-3. APMIS. 2009 Jul; 117(7): 492-9.

Durham-Colleran, M.W., Verhoeven, A.B., M.L. van Hoek. Francisella novicida Forms in vitro Biofilms Mediated by an Orphan Response Regulator. Microbial Ecology, September 2009.

Jawaid, S., Seidle, H., Zhou, W., Abdirahman, H., Abadeer, M. Hix, J., van Hoek, M.L. and Couch, R., “Kinetic Characterization and Phosphoregulation of the Francisella tularensis 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (MEP Synthase), PLOS One, 14 Dec 2009.

Ahmad S, Hunter L, Qin A, Mann BJ, van Hoek ML. Azithromycin effectiveness against intracellular infections of F

Amer LS, Bishop BM, van Hoek ML. Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella. Biochem Biophys Res Commun. 2010 Apr. [Selected for Faculty of 1000 review].

de Latour FA, Amer LS, Papanstasiou EA, Bishop BM, van Hoek ML. Antimicrobial activity of the Naja atra cathelicidin and small peptides. Biochem Biophys Res Commun. 2010 Apr 30.

A.B. Verhoeven, M. Durham-Colleran, W. Boswell, T. Pierson and M.L. van Hoek. Francisella philomiragia infects and replicates within the amoeba A. castellanii. Biological Bulletin. 2010 Oct;219(2):178-88.

T. Pierson, Matrakas D, Taylor YU, Manyam G, Morozov VN, Zhou W, van Hoek, ML. Proteomic Characterization and Functional Analysis of Outer Membrane Vesicles of Francisella novicida Suggests Possible Role in Virulence and Use as a Vaccine. J Proteome Res. 2010 Dec 7.

Dean, S.N., Bishop, B.M., van Hoek, ML. Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphyloccus aureus. BMC Microbiology. May 23, 2011. [“Highly Accessed” paper].

Dean, S.N., Bishop, B.M., van Hoek, ML. Susceptibility of Pseudomonas aeruginosa biofilm to alpha-helical peptides: D-enantiomer of LL-37. Frontiers in Cellular and Infection Microbiology. E-pub May 24, 2011.

Amaya M, Baranova A, van Hoek ML. Protein prenylation: a new mode of host-pathogen interaction. Biochem Biophys Res Commun. 2011 Dec 9;416(1-2):1-6. doi: 10.1016/j.bbrc.2011.10.142. Epub 2011 Nov 6. Review. PMID: 22079293

Bradburne CE, Verhoeven AB, Manyam GC, Chaudhry SA, Chang EL, Thach DC, Bailey CL, van Hoek ML. Temporal transcriptional response during infection of Type II alveolar epithelial cells with Francisella tularensis LVS supports a general host suppression and bacterial uptake by macropinocytosis. J Biol Chem. 2013 Jan 15.

Mackie RS, McKenney ES, van Hoek ML. Resistance of Francisella novicida to fosmidomycin associated with mutations in the glycerol-3-phosphate transporter. Front Microbiol. 2012;3:226. doi: 10.3389/fmicb.2012.00226. Epub 2012 Aug 13. PMID: 22905031

McKenney ES, Sargent M, Khan H, Uh E, Jackson ER, San Jose G, Couch RD, Dowd CS, van Hoek ML. Lipophilic prodrugs of FR900098 are antimicrobial against Francisella novicida in vivo and in vitro and show GlpT independent efficacy. PLoS One. 2012;7(10):e38167. doi: 10.1371/journal.pone.0038167. Epub 2012 Oct 15. PMID: 23077474

Richard J. Byers, Steven R. Medley, Michael L. Dickens, Kent C. Hofacre, Melanie A. Samsonow and Monique L. van Hoek, Transfer and Reaerosolization of Biological Contaminant following Field Technician Servicing of an Aerosol Sampler Research Article  J Bioterr Biodef 2013, S3:011

JSTO-In the News (CBS Input – December 2012)

DTRA Funded Effort Studies Anti-infective Properties of Reptile Serum

Seven months ago, DTRA initiated a research effort to take advantage of the anti-infective properties of reptile serum. The concept is to identify and use constitutive parts of serum that enables animals to fight infection, notably cationic antimicrobial peptides. These peptides will be isolated using a novel, nanoparticle-based approach.

The foundation for this DTRA-funded work is research performed at George Mason University (GMU) in the laboratories of Dr. Monique van Hoek (National Center for Biodefense and Infectious Diseases) and Dr. Barney Bishop (Department of Chemistry) that demonstrated anti-microbial and anti-biofilm properties of these CAMPs. Recently, their published work has been recognized by the respective journals as being among the highest viewed articles.  For example, their paper in Frontiers in Microbiology has received 1391 views [1]. The companion paper in BMC Microbiology was “Highly Accessed” with 5647 views so far [2], and a second companion paper in BBRC received a favorable score in a Faculty of 1000 review [3,4]. All of the researchers and students involved are very excited to be working on this project. The principal investigator on the project HDTRA1-12-C-0039 “Translational Peptides for Personal Protection” is Dr. Joel Schnur. (POC Al Graziano, 767-3360)

1. Dean, S. N., Bishop, B. M., & Van Hoek, M. L. (2011). Susceptibility of Pseudomonas aeruginosa biofilm to alpha-helical peptides: D-enantiomer of LL-37. Frontiers in Microbiology, 2.

2. Dean, S. N., Bishop, B. M., & van Hoek, M. L. (2011). Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus. BMC Microbiology, 11(1), 114.

3. Amer, L. S., Bishop, B. M., & van Hoek, M. L. (2010). Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella. Biochemical and Biophysical Research Communications, 396(2), 246-251.

4. http://f1000.com/prime/6167956

Awards

1.  2013 OSCAR Mentoring Excellence Award

http://oscar.gmu.edu/fac-staff/oscar-mentor-award.cfm

2. College of Science Teaching Award Apr 2012

Awarding Authority: George Mason University College of Science

Website: http://cos.gmu.edu/news/spring-12/college-science-publication-teaching-awards

The Teaching Award recognizes COS faculty members at George Mason University who are outstanding teachers or mentors or who have made major contributions to COS educational activities during the 2010–2011 academic year.

3. J. Shelton Horsley Research Award  01 May 2009

Awarding Authority: Virginia Academy of Science

Website: http://www.vacadsci.org/funding2010/Horsley.pdf

The J. Shelton Horsley Research Award is the highest honor bestowed by the Virginia Academy of Science for original research. The presentation of a certificate and a monetary award are a highlight of the Annual Meeting.