Steven R Blanke
Professor of Microbiology
Genetics, Host-Pathogen Interactions, Membrane Biology, Microbial Physiology, Molecular Immunology, Receptor Biochemistry, Signal Transduction, Toxins
B.A. (Biochemistry), Virginia Tech University 1982
Ph.D. (Biochemistry), University of Illinois, 1989
Postdoctoral (Microbiology and Molecular Genetics), Harvard Medical School, 1990-1995
Infection Biology and Cancer, Host-pathogen Interactions, Bacterial Pathogenesis, Bacterial Toxins
Modulation of host cells and tissues by bacterial toxins
Many pathogenic bacteria generate protein toxins that modulate properties of host cells and tissues in order to create a more suitable niche for colonization and, in some cases, to persist for extraordinary periods of time. We are studying the cellular intoxication mechanisms and structure-function relationships of several toxins that, to be successful, must traverse the membrane barrier into human cells. We are especially interested in investigating mechanisms of cellular entry and trafficking, as well as the action of toxins on immune cells. Current model systems in the laboratory include the vacuolating cytotoxin (VacA0 from Helicobacter pylori, the cytolethal distending toxins, and a novel toxin we have recently discovered from Helicobacter pylori.
Molecular and cellular basis of chronic bacterial infections
There is particular interest in understanding mechanisms that allow pathogenic organisms to persist within the host during chronic infection. An emerging paradigm is that persistent organisms are highly adaptive because they have co-evolved with their hosts. As a model system, the Blanke Laboratory is focusing on persistent infection in humans with the gastric pathogen, Helicobacter pylori, which is a significant risk factor for the development of gastric ulcer disease and stomach cancer. Because nearly half the world's population is infected with H. pylori, and because of increasing antibiotic resistance, gastric diseases caused by these micro-organisms are an important biomedical problem. Current research is focused on the contributions of a bacterial toxin (VacA) produced by H. pylori towards remodeling the host environment to create a more suitable niche to colonize and persist for the lifetime of the host in the absence of medical intervention. In addition, there is ongoing research to identify mechanisms by which H. pylori organisms are remodeled to become more adaptive to the stomach. These mechanisms include the capacity of H. pylori to sequester host cholesterol, and to change very rapidly to adapt to changes within the stomach.
Intracellular lifestyles of pathogenic bacteria
We are investigating mechanisms by which pathogenic bacteria not only survive encounters with host immune cells, but are able to exploit these cells by entering, surviving, and in some cases, replicating and escaping. Our model system is Bacillus anthracis, the causative agent of inhalation anthrax. The Blanke laboratory has been investigating the mechanisms by which B. anthracis enters the human lung and exploits the immune response in order to cause disease. Current work centers on the interaction of B. anthracis spores with human cells, and the capacity of B. anthracis to exploit the intracellular phagolysosome environment to germinate and replicate.
Induction of "limited damage" within the host
We are interested in strategies used by pathogenic bacteria to limit damage within the host as a strategy for promoting infection or persistence. We are focusing on mechanisms by which pathogenic organisms are capable of manipulating the human cell cycle through the action of a relatively new family of bacterial toxins, called the cytolethal distending toxins. We are investigating the cellular intoxication mechanisms, structure-function relationships, and evolutionary relationships between these toxins.
The Blanke Laboratory has undertaken research, associated with the IGB Host-Microbe Systems Theme, to study the dynamic interactions between the host and its commensal as well as pathogenic microbes to elucidate basic processes of disease and commensalism. This research will initially focus on the complex ecosystem of the vaginal microbiota and its impact on health and disease in women.
Development of molecular countermeasures targeting pathogenic bacteria
The ultimate goal of the basic science conducted within the Blanke laboratory is to develop new countermeasures against pathogenic organisms. Current projects, which are highly collaborative, target B. anthracis, the botulinum neurotoxins, the cytolethal distending toxins, VacA, and H. pylori.
RESEARCH & SCHOLARSHIP AWARDS
2015 Fellow of the American Academy of Microbiology
2014 Faculty Excellence Award (one award given per year within the
School of Molecular and Cellular Biology
at the University of Illinois).
2004 Award for Excellence in Research and Scholarship at the Associate Professor
Level - University of Houston (one university award per year at each academic rank).
2002 Award for Excellence in Research and Scholarship at the Assistant Professor
Level - University of Houston (one university award per year at each academic rank).
1999 Young Investigator Award, 10th International Meeting Campylobacter & Helicobacter.
1997 Natural Science and Mathematics Alumni Association Award.
1996 Oakridge Junior Faculty Award for Life Sciences Research.
1981 NSF Undergraduate Research Award.
TEACHING AWARDS AND RECOGNITION
2010, 2013 Cited as a Teacher ranked as outstanding by their students for Molecular and
Cellular Biology/Life Sciences and College of Medicine Courses.
2008, 2009 Cited as a Teacher ranked as excellent by their students for Molecular and
2011, 2012 Cellular Biology/Life Sciences and College of Medicine Courses.
1999 Teaching Excellence Award, College of Natural Sciences and Mathematics.
1998-1999 University of Houston Enron Award for Excellence in Teaching at the University level.
RECENT LECTURESHIPS, MEETING CHAIRS, LEADERSHIP POSITIONS
2015 Vice-Chair, Gordon Conference on Chemical & Biological Terrorism Defense, Ventura, CA,
2013 Chair, Bacteria-Host Interactions (2013) 2013 International Conference on
Bacillus anthracis, B. cereus, and B. thuringiensis, Victoria, Canada, September 2, 2013.
2013-2014 Chair, Division B (Microbial Pathogens) of ASM.
2013 Discussion Leader/Session Chair, Organizing Committee, 2013 Gordon Conference on
Chemical & Biological Terrorism Defense, Ventura, CA, March 10-15, 2013.
2012-2013 Chair Elect, Division B (Microbial Pathogens) of ASM, 2012-2013.
2011 Session Chair, Organizing Committee, 2011 International Conference on Campylobacter,
Helicobacter, and Related Organisms, Vancouver, British Columbia, Canada,
August 28 – September 1, 2011.
2011 Keynote Speaker, 23rd Annual Buffalo Conference on Microbial Pathogenesis –
Witebsky Center for Microbial Pathogenesis and Immunology (2011) Of Persistence,
Cancer, and Asthma: The Curious Case of Helicobacter pylori, Buffalo, NY,
April 29, 2011.
2011 Organizing Committee, and Discussion Leader/Session Chair, 2011 Gordon Conference
on Chemical & Biological Terrorism Defense, Ventura, CA, March 20-25, 2011.
Gillespie, E.J., Ho, C.-L. C., Balaji, K., Li, Z., Thomas, D., Clemens, D. L., Deng, G.,. Wang, Y. E., Elsaesser, H. J., Tamilselvam, B., France, B., Camberlain, B. T., Blanke, S. R., Cheng, G., de la Torre, J. C., Brooks, D. G., Jung, M. E., Manchester, M., Zink, J. I., Colicelli, J., Damoiseaux, R., & Bradley, K. A. (2013) A selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses protects rats from anthrax toxin. Proc. Natl. Acad. Sci. USA, under revision.
Gargi, A., Powers, B, Tamilselvam, B., Prouty, M. G., Lincecum, T., Maldonaldo-Arocho, F. J., Eshraghi, A., Wilson, B. A., Bradley, K. A., & Blanke, S. R. (2013) Cellular interactions of the cytolethal distending toxins from Escherichia coli and Haemophilus ducreyi, Journal of Biological Chemistry 288, 7492-7505. PMCID: PMC3597790.
Jain, P., Luo, Z.-Q., & Blanke, S. R. (2011) Helicobacter pylori VacA engages the mitochondrial apoptotic machinery by inducing Drp1-mediated mitochondrial fission, Proc. Natl. Acad. Sci. USA 108, 16032-16037. PMCID: PMC3179038.
Han, H., Hemp, J., Pace, L., Ouyang, H., Ganesan, K., Roh, J. H, Daldal, F., Blanke, S. R., & Gennis, R. (2011) Adaptation of aerobic respiration to low O2 environments. Proc. Natl. Acad. Sci. USA 108, 14109-14114. PMCID: PMC3161551.
Gut, I, Blanke, S. R., and van der Donk, W. (2011) Mechanism of Inhibition of Bacillus anthracis Spore Outgrowth by the Lantibiotic Nisin, Chemical Biology 6, 744-752. PMCID: PMC3178273.
Gupta, V. R., Wilson, B. A., & Blanke, S. R. (2010) Sphingomyelin is important for the uptake and intracellular trafficking of the Helicobacter pylori VacA, Cellular Microbiology 12, 1517-1533. PMCID: PMC2980835.
Nossa, C. W., deMurcia, G., Jain, P., Chen, L.- F., Desnoyers, S., & Blanke, S. R. (2009) Activation of the intrinsic catalytic activity of the nuclear factor, poly(ADP-ribose) polymerase-1, by Helicobacter pylori both in vitro and during infection. Proc. Natl. Acad. Sci. U S A 106, 19998-20003.
Blanke, S. R. (2009) Expanding functionality within the Looking Glass Universe. Science 325, 1505-1506.
Lamb A., Yang, X. -D., Tsang, Y. –H., Li, J. –D., Higashi, H., Hatakeyama, M., Peek, R. M., Blanke, S. R., and Chen, L. –F. (2009) Helicobacter pylori CagA stimulates NF-kB by activating TAK1 via TRAF6-mediated K63-ubiquitination. EMBO Reports, 10, 1242-1249.
Barua, S., McKevitt, M., DeGuisti, K., Hamm, E. E., Larabee, J., Shakir, S., Bryant, K., Spies MA, Reese JG, Dodd D, Pankow KL, Blanke SR, Baudry J. (2009) Determinants of Catalytic Power and Ligand Binding in Glutamate Racemase. J Am Chem Soc. 131, 5274-5284.
Kim, T. K., Thomas, S. M, Ho, M., Sharma, S., Reich, C. I., Frank, J. A., Yeater, K. M., Biggs, D., Nakamura, N., Stumpf, R., Leigh, S. R., Tapping, R. I., Blanke, S. R., Slauch, J. M., Gaskins, H. R., Weisbaum, J. S., Olsen, G. J., Hoyer, L. L., and Wilson, B. A. (2009) Heterogeneity of vaginal microbial communities within individuals. Journal of Clinical Microbiology 47, 1181-1189.
Gupta, V. R., Patel, H. K., Kostolansky, S. S., Ballivian, R. A., Eichberg, J., and Blanke, S. R. (2008) Sphingomyelin Functions as a Novel Receptor for Helicobacter pylori VacA, PLoS Pathogens 4, e1000072, 1-12.
Blanke, S. R., & Cover, T.L. (2008) Helicobacter pylori vacuolating toxin, in Molecular Genetics of Helicobacter, Yamaoka, Y (ed.) Horizon Scientific Press, UK, 87-114.
Ampapathi, R. S., Lou, D. I., Creath, A. L., Blanke, S. R., & Legge, G. B. (2008) Order - Disorder - order transitions mediate the activation of cholera toxin. Journal of Molecular Biology 377, 748-760.
Ye, D., & Blanke, S. R. (2006) Bacterial toxins as Cellular Modulators, in Molecular Paradigms of Infectious Disease: A Bacterial Perspective, C. A. Nickerson, M. Schurr (eds.), 321-403; Springer Press, US.
Blanke, S. R. (2006) Portals and pathways: Principles of bacterial toxin entry into cells, Microbe 1, 26-32.
Blanke, S. R. (2005) Micro-managing the Executioner: Pathogen Targeting of Mitochondria, Trends in Microbiology 13, 64-71.
Cover, T.L., & Blanke, S. R. (2005) Helicobacter pylori VacA as a paradigm for toxin multifunctionality, Nature Reviews Microbiology 3, 320-332.
Willhite, D.C., Cover, T.L., & Blanke, S.R. (2003) Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation, J. Biol. Chem. 278, 48204-48209.
Blanke, S. R., Milne, J. C., Benson, E. L., & Collier, R. J. (1996) Fused polycationic peptide mediates delivery of diphtheria toxin A chain to the cytosol in the presence of anthrax protective antigen, Proc. Natl. Acad. Sci. USA 93, 8437-8442. PMCID: PMC38689.
Wilson, B. A., Blanke, S. R., Murphy, J. R., Pappenheimer, A. M., and Collier, R. J. (1990) Does Diphtheria Toxin have Nuclease Activity? Science 250, 832-838.