I have had the great honor of being involved with research projects that study the virulence mechanisms of different pathogens. I have performed my research using diverse microbiological and biochemical techniques; I have even contributed to refinement of some of those techniques such as: isolation and purification of the biofilm producing components curli-fimbriae and Cellulose of Enterobacteriaceae, and transformation of linear DNA into Francisella. I have a keen knowledge of laboratory regulations, including Biosafety laboratory level 3 (BSL-3). I have seven years of teaching experience, and I am actively involved in Student Advising and other University activities.

Education

University of Braunschweig, Germany

Diplom-Biologe

1999

Biology

German Research Centre for Biotechnology and UB, Germany

Ph.D.

2004

Molecular biology

Karolinska Institute, Stockholm, Sweden

Postdoc

2004-2005

Medical microbiology

University of Texas at San Antonio

Postdoc

2006-2008

Medical microbiology

Positions and Honors

2008 – (*) Present Assistant Professor of Research, University of Texas at San Antonio, Texas

(*) 06/2012 – 06/2014 Research Scientist-Microbiologist, US Army Medical Center, ISR/DTRD, Fort Sam Houston, Texas

2010 - Present Adjunct Professor, San Antonio College, San Antonio,Texas

2006 – 2008 Postdoctoral Researcher, University of Texas at San Antonio, Texas

2004 – 2005 Postdoctoral Researcher, Karolinska Institute, Stockholm, Sweden

1999 – 2004 Doctoral Studies (PhD), German Research Centre for Biotechnology and University of Braunschweig, Germany

Award - Outstanding Graduate Student Award from German Academic Exchange Service, November 2000

1995 – 1999 Undergraduate Studies (Diplom-Biologe), University of Braunschweig, Germany

Research Support

1. Characterization of the nadM gene in Francisella tularensis, the causative agent of Tularemia; SAAF (San Antonio Area Foundation), 07/2010-06/2011. Principal Investigator.

2. Prevention of bacterial biofilm infections in combat wounds and control of mixed species biofilm infections; Naval Medical Research Unit San Antonio, 07/01/2012 – 06/30/2013. Principal Investigator.

Publications

Selected Peer-reviewed Publications

1. Xhavit Zogaj, Manfred Nimtz, Manfred Rohde, Werner Bokranz and Ute Römling. The multicellular morphotypes of Salmonella Typhimurium and Escherichia coli produce cellulose as the second component of the extracellular matrix. Mol. Microbiol. 2001. Vol. 39. No. 6, p. 1452-1463.

2. Xhavit Zogaj, Werner Bokranz, Manfred Nimtz and Ute Römling. Production of Cellulose and Curli Fimbriae by Members of the Family Enterobacteriaceae Isolated from the Human Gastrointestinal Tract. Infect. and Immunity 2003. Vol. 71. No. 7, p. 4151–4158.

3. Ute Römling, Werner Bokranz, Wolfgang Rabsch, Xhavit Zogaj, Manfred Nimtz, Helmut Tschäpe. Occurrence and regulation of the multizellular morphotype in Salmonella serovars important in human disease. International Journal of Medical Microbiology (IJMM) 2003. Vol. 293, p. 273-285.

4. M. A. Barocchi, J. Ries, X. Zogaj, C. Hemsley, B. Albiger, A. Kanth, S. Dahlberg, J. Fernebro, M. Maschioni, V. Masignani, K. Hultenby, A. R. Taddei, K. Beiter, F. Wartha, A. von Euler, A. Covacci, D. W. Holden, S. Normark, R. Rappuoli and B. Henriques-Normark. A pneumococcal pilus influences virulence and host inflammatory responses. Proceedings of the National Academy of Sciences of the United States of America (PNAS) 2006. Vol. 103. No. 8, p. 2857-2862.

5. Jirong Liu, Xhavit Zogaj, Jeffrey R Barker, Karl E Klose. Construction of targeted insertion mutations in Francisella tularensis subsp. novicida. BioTechniques, 2007. Vol. 43, p. 487-492

6. Xhavit Zogaj, Subhra Chakraborty, Jirong Liu, David G. Thanassi, Karl E. Klose. Characterization of the Francisella tularensis subsp. novicida Type IV Pilus. Microbiol. 2008. Vol. 154. p. 2139-2150.

7. Leonardo Sorci, Darius Martynowski, Dmitry A. Rodionov, Yvonne Eyobo, Xhavit Zogaj, Karl E. Klose, Evgeni V. Nikolaev, Giulio Magni, Hong Zhang and Andrei L. Osterman. Francisella tularensis reveals a novel route of NAD synthesis. Proceedings of the National Academy of Sciences of the United States of America (PNAS) 2009 Mar 3;106(9):3083-8.

8. S.L. Rajasekhar Karna, Xhavit Zogaj, Jeffrey R. Barker, Janakiram Seshu, Simon L. Dove, and Karl E. Klose. A bacterial two-hybrid system that utilizes Gateway cloning for rapid screening of protein-protein interactions. BioTechniques, Vol. 49, No. 5, November 2010, pp. 831–833.

9. Xhavit Zogaj and Karl E. Klose. Genetic manipulation of Francisella tularensis. Frontiers in Microbiology, 01/2011, Vol. 1, 142.

10. Kalyan C. Nallaparaju, Jieh-Juen Yu, Stephen A. Rodriguez, Xhavit Zogaj, Srikanth Manam, M. Neal Guentzel, Janakiram Seshu, Ashlesh K. Murthy, James P. Chambers, Karl E. Klose, Bernard P. Arulanandam. Evasion of IFN-c Signaling by Francisella novicida is Dependent upon Francisella Outer Membrane Protein C. Plos One, March 2011, Volume 6, Issue 3, e18201.

11. Xhavit Zogaj, Geoff C. Wyatt, Karl E. Klose. cdGMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicida. Infection and Immunity 2012. P.4239-4247, Volume 80, Nr. 12.

12. Eppinger M, McNair K, Zogaj X, Dinsdale EA, Edwards RA, Klose KE. Draft Genome Sequence of the Fish Pathogen Piscirickettsia salmonis. Genome Announc. 2013, Nov 7, 1(6).

13. Nguyen, Jesse; Gilley, Ryan; Zogaj, Xhavit; Rodriguez, Stephen; Klose, Karl E. Lipidation of FPI Protein IglE is required for Francisella Intramacrophage Replication and Virulence. Phathog.Dis. 2014 Mar.

Book contribution

Medical implications of Biolfilms (edited by M. Wilson and D. Devine), Cambridge University Press. 2003, England. Kap.: 231–261. Dissection of the Genetic Pathway Leading to Multicellular Behavior in Salmonella enterica Serotype Typhimurium and other Enterobacteriaceae.

Poster and oral presentations

Xhavit Zogaj, Manfred Nimtz, Manfred Rohde, Werner Bokranz and Ute Römling. The multicellular morphotypes of S. typhimurium produce cellulose. VAAM-Tagung: Oktober 2001. Osnabrück, Germany.

Xhavit Zogaj, Jirong Liu, Siva T. Sarva, Robert H. Waldo, Subhra Chakraborty, Jeffrey R. Barker, David G. Thanassi, George M. Hilliard, Eric de Waal and Karl E. Klose. The virulence regulatory protein MglA also regulates pili expression in Francisella tularensis. 5th International Conference on Tularemia. November 1-4, 2006. Woods Hole, MA.

Xhavit Zogaj. NAD Pathway in Francisella tularensis. South Texas Center for Emerging Infectious Diseases (STCEID) - Spring Conference. May 2008. Mayan Dude Ranch, Bandera/Texas

Xhavit Zogaj, Subhra Chakraborty, Jirong Liu, David G. Thanassi and Karl E. Klose Type IV Type IV Pilus of Francisella tularensis subsp. Novicida. Fall Meeting of the Texas/South Central Branches of The American Society for Microbiology. Nov 9-11, 2008 University of Texas at Austin.

Xhavit Zogaj, Leonardo Sorci, Andrei L. Osterman and Karl E. Klose. Characterization of NAD Biosynthesis in F. tularensis. The American Society for Microbiology (ASM), May 23-27, 2010, San Diego, California.

Xhavit Zogaj, Geoff C. Wyatt, Karl E. Klose. cdGMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicida. cdGMP stimulates Biofilm Formation and inhibits virulence of Francisella novicida. 1st Annual Conference of the San Antonio Vaccine Development Center. November 16, 2012

Research Statement:

Research Assistant Professor at UTSA. I have focused my research on two projects: 1) Genetic Analysis of the NAD Biosynthesis Pathway in Francisella. Nicotinamide Adenine Dinucleotide (NAD) is an essential coenzyme found in all living cells and thus the enzymes involved in NAD metabolism are therapeutic targets. We have shown (in collaboration with Dr. Andrei Ostermann, an internationally recognized scientist in genomics, at the Burnham Institute for Medical Research) that Francisella has a unique pathway for NAD biosynthesis (Sorci et al. PNAS 2009. 3083-3088). We have further characterizing NadM, the most important protein associated with NAD synthesis. NadM has two independent active domains. The first domain, NMN adenylyltransferase, is essential for NAD production and therefore also for Francisella survivor. The second domain, C-terminal ADP-ribose pyrophosphatase (ADPRase), recycles the NAD and thus keeps NAD equilibrium within the cell. Our data shows that a Francisella strain with the ADPRase domain inactivated is highly attenuated for virulence in mice, suggesting a role for this domain in Francisella pathogenesis.

2) The role of c-di-GMP in biofilm formation and virulence of Francisella. Secondary messenger molecule bis- (3-5)-cyclic dimeric GMP (c-di-GMP) is involved in the regulation of bacterial biofilm formation and virulence in many bacterial species. Interestingly the highly virulent strain Francisella tularensis subsp. tularensis (Ftt) does not contain genes known to encode proteins that synthesize c-di-GMP. However, Francisella tularensis subsp. novicida (Ftn) strain, which is highly homologous to Ftt - but avirulent in humans, has genes that encode two proteins required to synthesize and degrades c-di-GMP. We hypothesize that the differences in human virulence between Ftt and Ftn may be due in part to the absence of c-di-GMP signaling in Ftt (Zogaj et al., December 2012, Infect. and Immun. p. 4239–4247, Volume 80, Number 12).

Research Scientist - Microbiologist at BAMC. My research was aimed at developing Methods of prevention of bacterial biofilm infections in combat wounds and control of mixed species biofilm infections.

Bacterial biofilms are assemblies of bacteria that are held together by their extracellular polymeric substances (EPS). The expression of EPS is regulated by c-di-GMP, a small intracellular molecule. Biofilms can adhere to abiotic or biotic surfaces. Also, they can colonize catheters and implants, or they can even colonize directly organs or tissues within our body. Bacterial biofilms are considered as a source of infection. Bacteria within biofilms are protected, and therefore much higher antibiotic concentrations are needed in order to neutralize them. The rise of multidrug resistant species makes the treatment of bacterial biofilms even more complicated.

Pseudomonas aeruginosa, Klebsiella pneumonia and Acinetobacter baumanni are the most common bacteria known to produce a mixed-bacterial biofilm on the wounds. At the San Antonio Military Medical Center I was involved in developing a GFP reporter system that will be utilized to characterize all pathogens within a mature mixed biofilm.

Postdoc. at UTSA. As a postdoc at UTSA I have focused my research on the project Characterization of type IV pilus genes: the role that they play in Francisella virulence and in the secretion of proteins via the tfp-dependent secretion system. The results achieved from this project have been published in Microbiology (Zogaj et al. Microbiol. 2008. Vol 154. 2139-2150).

Postdoc. at Karolinska Institute. During postdoctoral studies in the laboratory of Dr. Birgitta Henriques-Normark I was involved in a project to explore the pilus expression of the gram-positive bacterium Streptococcus pneumoniae. In this study we showed that the pilus support the bacterial attachment into the host cells and consequently increases the ability of S. pneumoniae to cause invasive disease. We provided evidence that the pilus is a virulence factor of S. pneumoniae. These findings were published in Proceedings of the National Academy of Sciences (Barocchi et al. PNAS. 2006. Vol. 103. 2857-2862).

Doctoral dissertation. The research project of my Ph.D. thesis was to study and characterize curli and cellulose, two extracellular matrix components of S. typhimurium and Escherichia coli. The co-expression of these two components leads to formation of highly solid, hydrophobic bacterial biofilms. Curli are proteinaceous fibers that bind to the host proteins laminin, plasminogen and fibronectin. Interestingly, curli fibers share related characteristics with the medically pathogenic amyloid fibers that are involved in Alzheimer and prion diseases. Cellulose is an organic polysaccharide found in all plants and in cellulose-producing bacteria like Acetobacter, Agrobacter, Rhizobium and Sarcina. Using genomic and microbiological methods we have identified cellulose biosynthesis genes in Salmonella and E. coli, and have also shown that these bacteria, under certain conditions, can synthesize cellulose. Our publication in Molecular Microbiology was the first scientific report, which described the cellulose biosynthesis in enterobacteriaceae (Zogaj et al. Mol. Micro. 2001. Vol. 39. 1452-1463). Subsequently, we were able to show that cellulose, as a component of the extracellular matrix, is also expressed by other enterobacteria like Salmonella enteritidis, Escherichia coli, Klebsiella pneumoniae, Citrobacter spp. and Enterobacter sakazakii (Zogaj et al. Infection and Immunity 2003. Vol. 71. 4151–4158). After 4 ½ years of research work I completed my Ph.D. project and wrote the dissertation titled: “Identifizierung der Biofilm Komponente Cellulose und Analyse der Curli-Fimbrien Expression bei Enterobakterien” (Dissertation is in German and can be found at: http://www.digibib.tu-bs.de/?docid=00001634, Published by University library of TUBS).