Department of Veterinary Pathobiology

Alexander W.E. Franz
Assistant Professor
Ph.D.

  • BS: Christian-Albrechts-University, Kiel Germany
  • Ph.D.: Christian-Albrechts-University, Kiel Germany
  • Postdoctoral Fellowships: Plant Research International, Wageningen, Netherlands;Purdue University, IN; Colorado State University, CO

Building Address: 303 Connaway Hall
Phone Number: (573) 884-2635
Email: franza@missouri.edu

Research Emphasis:

The research work in my laboratory focuses on the molecular interactions of arthropod-borne (arbo)viruses such as dengue, chikungunya, Zika viruses with the yellow fever mosquito, Aedes aegypti. These mosquito-borne viruses are important human pathogens, which have been responsible for recent explosive disease outbreaks throughout the tropical regions of the world.  

Our goal is to understand the molecular basis of mosquito vector competence for arboviruses to develop novel strategies aiming at interrupting the viral disease cycle in the insect. One research effort focuses on the mosquito’s innate RNA interference (RNAi) pathway. We investigate how RNAi modulates arbovirus infections and how the RNAi pathway can be manipulated to block arbovirus replication in relevant mosquito tissues. An important tool for this research is the germline transformation of Ae. aegypti.  As a proof-of-principle study for a novel control strategy in the field, we previously generated transgenic Ae. aegypti, which are refractory to dengue 2 virus by tissue-specifically triggering the RNAi pathway against the virus.

Another research project addresses a long-standing question in arbovirology/vector biology: how do arboviruses traverse the tissue (organ) barriers in their insect vectors? Specifically, we are looking at the mechanism(s) underlying the dissemination of arboviruses from the midgut of Ae. aegypti. Observations with chikungunya virus, an alphavirus, indicate that the midgut basal lamina acts as a barrier for the virus and becomes permissive during bloodmeal digestion allowing virions to exit the midgut. Enzymatic activity is likely required to facilitate extracellular matrix rearrangements, which affect the midgut permissiveness for the virus. Recently, our laboratory has obtained funding from NIH for a five year period to further pursue this exciting research project.

In a continuous effort we are investigating novel approaches to optimize transgene expression in Ae. aegypti, including the use of site-specific integration technology, novel tissue-specific promoters, and gene-knockdown/knockout strategies. For the first time, we successfully applied the CRISPR/Cas9 system in mosquitoes to stably disrupt the coding sequence of a gene.   

A collaboration between our lab and the research group of Dr. Michael Roberts (Life Sciences Center of MU) has been established to investigate the pathobiology of Zika virus in differentiated human embryonic stem cells representing the primitive placental trophoblast. The idea behind this research is to establish a model system to reveal why certain strains of Zika virus can cause birth defects in humans such as microcephaly whereas other viral strains do not seem to cause similar fetal damage.

Teaching Responsibilities: Course Director for MICROB 4303/7303 "Fundamental Virology"; lecturer in MICROB 9001 "Topics in Microbiology - Advanced Virology"

Selected Publications:

  1. Sheridan, M.A., Balaraman, V., Schust, D.J., Ezashi, T., Roberts, R.M., Franz, A.W.E. (2018). African and Asian strains of Zika virus differ in their ability to infect and lyse primitive human placental trophoblast. Virology [under review].
  2. Dong, S., Balaraman, V., Kantor, A.M., Lin J., Grant, D.G., Held, N.L., Franz, A.W.E. (2017). Chikungunya virus dissemination from the midgut of Aedes aegypti is associated with temporal basal lamina degradation during bloodmeal digestion. PLoS Neglected Tropical Diseases 11(9): e0006976.
  3. Dong, S., Behura, K.S., Franz, A.W.E. (2017). The midgut transcriptome of Aedes aegypti fed with saline or protein meals containing chikungunya virus reveals genes potentially involved in viral midgut escape. BMC Genomics 18: 382.
  4. Sheridan, M.A., Yunusov, D., Balaraman, V., Alexenko, A.P., Yabe, S., Verjovski-Almeida, S., Schust, D.J., Franz, A.W., Sadovsky, Y., Ezashi, T., Roberts, R.M. (2017). Vulnerability of primitive human placental trophoblast to Zika virus. Proc Natl Acad Sci U S A. 114(9):E1587-E1596.
  5. Kantor, A.M., Dong, S., Held, N.L., Ishimwe, E., Passarelli, A.L., Clem, R.J., Franz, A.W.E. (2017). Identification and initial characterization of matrix metalloproteinases in the yellow fever mosquito, Aedes aegypti. Insect Molecular Biology 26 (1), 113-126.
  6. Dong, S., Kantor, A.M., Lin, J., Passarelli, A.L., Clem, R.J., Franz, A.W.E. (2016). Infection pattern and transmission potential of chikungunya virus in two New World laboratory-adapted Aedes aegypti strains. Scientific Reports 6: 24729.
  7. Olson, K.E. and Franz, A.W.E. (2016). Genetically Modified Vectors for Control of Arboviruses. In: ‘Nikolaos Vasilakis and Duane Gubler, (eds.), Arboviruses: Molecular Biology, Evolution and Control’, Caister Academic Press, Norwich, U.K., 398 pp.
  8. Franz, A.W.E., Kantor, A.M., Passarelli, A.L., Clem R.J. (2015). Tissue barriers to arbovirus infection in mosquitoes. Viruses 7(7), 3741-3767.
  9. Olson, K.E. and Franz, A.W.E. (2015).  Advances in genetically modified Aedes aegypti to control transmission of dengue viruses. Future Virology 10(5), 609-624. 
  10. Dong, S., Lin, J., Held, N.L., Clem, R.J., Passarelli, A.L., Franz, A.W.E. (2015). Heritable CRISPR/Cas9-mediated genome editing in the yellow fever mosquito, Aedes aegypti. PLoS One 10(3): e0122353.
  11. Franz, A.W.E., Balaraman, V., Fraser, M.J. (2015). Disruption of dengue virus transmission by mosquitoes. Current Opinion in Insect Science 6, 1-9.
  12. Franz, A.W.E., Sanchez-Vargas, I., Raban, R.R., Black, IV, W.C., James, A.A., Olson, K.E. (2014).  Fitness impact and stability of a transgene conferring resistance to dengue-2 virus following introgression into a genetically-diverse Aedes aegypti strain. PLoS Neglected Tropical Diseases 8(5): e2833. 
  13. Franz, A.W.E., Clem, R.J., Passarelli, A.L. (2014). Novel genetic and molecular tools for the investigation and control of dengue virus transmission by mosquitoes. Current Tropical Medicine Reports 1(1), 21-31.   
  14. Steel, J.J., Franz, A.W.E., Sanchez-Vargas, I., Olson, K.E., Geiss, B.J. (2013). Subgenomic reporter RNA system for detection of alphavirus infection in mosquitoes. PLoS One 8(12), e84930.
  15. Khoo, C.C.H., Doty, J.B., Held, N.L., Olson, K.E., Franz, A.W.E. (2013). Isolation of midgut escape mutants of two American genotype dengue 2 viruses from Aedes aegypti. Virology Journal 10(1):257.
  16. Khoo, C.C.H., Doty, J.B., Heersink, M.S., Olson, K.E., Franz, A.W.E. (2013). Transgene-mediated suppression of the RNA interference pathway in Aedes aegypti interferes with gene silencing and enhances Sindbis virus and dengue virus type 2 replication. Insect Molecular Biology 22(1), 104–114.
  17. Franz, A.W.E., Jasinskiene, N., Sanchez-Vargas, I., Isaacs, A.T., Smith, M.R., Khoo, C.C.H., Heersink, M.S., James, A.A., Olson, K.E. (2011). Comparison of transgene expression in Aedes aegypti generated by mariner Mos1 transposition and PhiC31 site-directed recombination. Insect Molecular Biology 20(5), 587-598.
  18. Khoo, C.C.H., Sanchez-Vargas, I., Piper, J., Olson, K.E., Franz, A.W.E. (2010). The RNAi pathway affects midgut infection- and escape barriers for Sindbis virus in Aedes aegypti. BMC Microbiology, 10:130. 
  19. Franz, A.W.E., Sanchez-Vargas, I., Piper, J., Smith, M.R., Khoo, C.C.H., James, A.A., Olson, K.E.  (2009). Stability and loss of a virus resistance phenotype over time in transgenic mosquitoes harboring an antiviral effector gene. Insect Molecular Biology 18(5), 661-672.
  20. Sanchez-Vargas, I., Scott, J.C., Poole, B.K., Franz, A.W.E., Barbosa-Solomieu, V., Wilusz, J., Olson, K.E., Blair, C.D. (2009). Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito’s RNA interference pathway. PLoS Pathogens 5, e1000299. 
  21. Franz, A.W.E., Sanchez-Vargas, I., Adelman, Z.N., Blair, C.D., Beaty, B.J., James, A.A., Olson, K.E. (2006). Engineering RNAi-based transgenic resistance against dengue virus type 2 in Aedes aegypti. Proceedings of the National Academy of Sciences of the U.S.A. 103(11), 4198-4203.

 

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