Jonathan Hansen, MD, PhD

Jonathan Hansen, MD, PhD

Assistant Professor
7341B MBRB
CB #7032
919-843-5854 - office
919-843-2659 - fax



 Research

Current research indicates that inflammatory bowel diseases (IBD’s), including Crohn’s disease and ulcerative colitis, are due to uncontrolled innate and adaptive immune responses to commensal intestinal bacteria in genetically susceptible hosts.  The role of bacteria in the pathogenesis of IBD’s is highlighted by genome-wide association studies that have identified 12 IBD susceptibility loci that overlap with those for mycobacterial infections (Jostins et al., Nature 2012).  Furthermore, in virtually all animal models of IBD tested to date, the presence of intestinal bacteria is necessary for the development of intestinal inflammation.

While it is becoming increasingly clear how commensal (non-pathogenic) intestinal bacteria initiate the chronic T-cell mediated intestinal inflammation observed in IBD’s and experimental colitis, their roles in the perpetuation and progression of disease is unclear.  Moreover, the effects of host inflammation on commensal bacterial physiology and virulence are unknown.  We hypothesize that commensal bacteria dynamically respond to intestinal inflammation in a manner that perpetuates or worsens disease.  For instance, bacterial antigens and adjuvants initiate intestinal inflammation, which in turn leads to the production of mediators including reactive oxygen species, inflammatory cells, and cytokines that consequently enhance the growth and virulence of the bacteria.

 

 

 

 Exploring this hypothesis will enhance our understanding of the pathogenesis of IBD’s and host-microbial interactions, and potentially identify new therapeutic targets for these currently incurable diseases.

Our lab focuses on the following main projects:

1)      Identification of inflammation-associated transcriptional responses in commensal intestinal bacteria during experimental colitis that impact the course of disease.  We use a combination of gnotobiotic (defined microbial environment) technology in mice, molecular biology, bacterial mutagenesis, dietary interventions, microarrays, microbial RNA-Seq, and ex-vivo immune cell assays to identify bacterial genes that are differentially expressed during inflammation and mechanisms of how these genes affect host immune responses.

 2)      Characterize how experimental colitis impacts the genetic microevolution of commensal intestinal bacteria.  We use gnotobiotic technology in mice, next generation bacterial genome sequencing, bacterial mutagenesis, high throughput bacterial phenotyping assays, and redox chemistry to identify genetic mutations that accumulate in bacteria during colitis, characterize their effect on protein function and bacterial physiology, and ultimately how mutations affect the growth and virulence of commensal bacteria during experimental colitis.

 Publications:

BOOKS AND CHAPTERS:

  1. J Hansen and R B Sartor.  Insights from animal models. In: Bernstein CN, ed. Inflammatory bowel disease yearbook, vol. 4. Chicago: Remedica; 2007:19-55.

 

ORIGINAL RESEARCH:

  1. Tchaptchet S, Fan TJ, Goeser L, Schoenborn A, Gulati AS, Sartor RB, Hansen JJ. Inflammation-Induced Acid-Tolerance Genes gadAB in Luminal Commensal Escherichia coli Attenuate Experimental Colitis, Infect Immun 2013; 81:3662-3671. PMCID 3811779
  2. Onyiah JC, Sheikh SZ, Maharshak N, Steinbach EC, Russo SM, Kobayashi T, Mackey LC, Hansen JJ, Moeser AJ, Rawls JF, Borst LB, Otterbein LE, Plevy SE.  Carbon Monoxide and Heme Oxygenase-1 Prevent Intestinal Inflammation in Mice by Promoting Bacterial Clearance, Gastroenterology 2013; 144:789-798. PMCID 3608700
  3. Arthur JC, Perez-Chanona E, Muehlbauer M, Tomkovich S, Uronis JM, Fan TJ, Abujamel T, Dogan B, Campbell BJ, Rogers AB, Rhodes JM, Simpson KW, Stintzi A, Hansen JJ, Keku TO, Fodor AA, Jobin C. Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota,  Science 2012; 338:120-123.
  4. Hansen JJ, Huang Y, Peterson DA, Goeser L, Fan TJ, Chang EB, and Sartor RB. The Colitis-Associated Transcriptional Profile of Commensal Bacteroides Thetaiotaomicron Enhances Adaptive Immune Responses to a Bacterial Antigen. PLoS One 2012; 7:e42645.
  5. Sigmon L, Greene K, Hansen JJ. IV Cyclosporine to Treat Refractory CVID Enteropathy. Scand J Gastroenterol 2012; 47:1396-1397.
  6. Patwa LG, Fan TJ, Tchaptchet S, Liu Y, Lussier YA, Sartor RB, Hansen JJ.  Chronic intestinal inflammation induces stress-response genes in commensal Escherichia coli.  Gastroenterology 2011; 141:1842-1851.
  7. Kobayashi T, Matsuoka K, Sheikh SZ, Elloumi HZ, Kamada N, Hisamatsu T,Hansen JJ, Doty KR, Pope SD, Smale ST, Hibi T, Rothman PB, Kashiwada M, Plevy SE.  NFIL3 is a regulator of IL-12p40 in macrophages and mucosal immunity.  J Immunol 2011; 186:4649-4655.
  8. Hansen J, Holt L, Sartor RB.  Gene Expression Patterns in Experimental Colitis in IL-10 Deficient Mice.  Inflamm Bowel Dis; 2009; 15:890-899.
  9. L Zhong, W Li, Z Yang, K Qing, M Tan, J Hansen, Y Li, L Chen, R Chan, C Bischof, N Maina, K Weigel-Kelley, W Zhao, S Larsen, M Yoder, W Shou, and A Srivastava.  Impaired Nuclear Transport and Uncoating Limit Recombinant Adeno-associated Virus 2 Vector-mediated Transduction of Primary Murine Hematopoietic Cells, Hum. Gene Ther 2004; 15:1207-1218.
  10. J Hansen, B J Ulmer, D K Rex.  Technical Performance of Colonoscopy in Patients Sedated with Nurse-administered Propofol, Am J Gastroenterol 2004; 99(1):52-56.
  11. B J Ulmer, J Hansen, C. A. Overley, M. R. Symms, V. Chadalawada, S. Liangpunsakul, E. Strahl, A. M. Mendel, and D K. Rex.  Propofol Versus Midazolam/Fentanyl for Outpatient Colonoscopy: Administration by Nurses Supervised by Endoscopists, Clin Gastroenterol Hepatol 2003; 1(6):425-432.
  12. K Qing, W Li, L Zhong, M Tan, J Hansen, K A Weigel-Kelley, L Chen, M C Yoder, and A Srivastava.  Adeno-Associated Virus 2-Mediated Gene Transfer: Role of Cellular T Cell Protein Tyrosine Phosphatase in Transgene Expression in Established Cell Lines In Vitro and Transgenic Mice In Vivo,  Journal of Virology 2003; 77(4):2741-2746.
  13. K Qing, J Hansen, M Tan, S Zhou, and A Srivastava, Adeno-Associated Virus Type 2-Mediated Gene Transfer: Role of Cellular FKBP52 Protein in Transgene Expression, Journal of Virology 2001; 75(19):8968-8976.
  14. J Hansen, K Qing, and A Srivastava, Infection of Purified Nuclei by Adeno-Associated Virus 2,  Molecular Therapy 2001; 4(4):289-296.
  15. J Hansen, K Qing, and A Srivastava, Adeno-Associated Virus Type 2-Mediated Gene Transfer: Altered Endocytic Processing Enhances Transduction Efficiency in Murine Fibroblasts, Journal of Virology 2001; 75(9):4080-4090.
  16. J Hansen, K Qing, H J Kwon, C Mah, and A Srivastava, Impaired Intracellular Trafficking of Adeno-Associated Virus Type 2 Vectors Limits Efficient Transduction of Murine Fibroblasts,  Journal of Virology 2000; 74(2):992-996.
  17. K Qing, C Mah, J Hansen, S Zhou, V Dwarki, and A Srivastava,  Human Fibroblast Growth Factor Receptor 1 is a Co-Receptor for Infection by Adeno-Associated Virus 2, Nature Medicine 1999; 5(1):71-77.
  18. C Mah, K Qing, J Hansen, B Khuntirat, M C Yoder, and A Srivastava,  Gene Transfer With Adeno-Associated Virus 2 Vectors: The Growth Factor Receptor Connection, Gene Therapy and Molecular Biology 1998; 3:57-65.

 

OTHER PEER REVIEWED ARTICLES:

  1. Tchaptchet S and Hansen JJ. The Yin and Yang of Host-Commensal Mutualism. Gut Microbes 2012; 2:1-6.
  2. Hansen JJ, Gulati A, Sartor RB.  The role of mucosal immunity and host genetics in defining intestinal commensal bacteria. Curr Opin Gastroenterol 2010; 26:564-71.
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