Brief Biography

Dr. Nicola Jones completed medical school at the University of Toronto in 1989 and training in paediatrics at The Hospital for Sick Children in Toronto in 1993. She completed clinical subspecialty training in gastroenterology at The Hospital for Sick Children (1993-1994) and subsequently underwent research training with completion of a PhD in Molecular and Medical Genetics at the University of Toronto (1995-1999).

Dr. Jones is currently the research Training Program Director in the Division of GI/Nutrition at The Hospital for Sick Children. Dr. Jones’s research program has been funded by support provided by the Canadian Institutes of Health Research (2001-present) and the American Digestive Health Foundation (2000-present).

Research Interests

Research interests include focussing on understanding disease pathophysiology following Helicobacter pylori infection.

Research Activities

A microbe, called Helicobacter pylori, infects the stomach in over half of the world’s population. Infection with H. pylori causes peptic ulcer disease and is also a risk factor for gastric cancers. We do not know how Helicobacter pylori causes disease. People with these bacteria in their stomach are infected for life unless they are treated with a complicated course of antibiotics that can cause side effects. This suggests that H. pylori avoids our immune system to cause chronic infection and disease. My laboratory is investigating how this bug escapes escapes elimination by our immune system by using cell culture techniques and by employing studies in mice that have a normal immune system and mice that have abnormalities in different parts of the immune system. This information will help us to understand how the bacteria causes disease so that we can target new therapies directly at these areas in order to decrease illness.

Significant research findings:

Despite the presence of a vigorous immune response, infection with H. pylori persists unless individuals receive specific eradication therapy. My research has focused on understanding the different mechanisms H. pylori utilizes to subvert host immune responses thereby resulting in disease and has resulted in several significant contributions in the field.

My research has demonstrated that H. pylori triggers immune-mediated cell death of gastric epithelial cells and that deregulation of this pathway promotes more severe gastric atrophy, the precursor to gastric cancer. These findings have important implications for understanding the mechanisms involved in the development of gastric cancers following H. pylori infection. I have also identified that H. pylori disrupts cytokine signalling to influence host immune responses and that manipulation of this signaling pathway plays a critical role in modifying susceptibility to H. pylori infection.

My research also demonstrated that H. pylori usurps the function of macrophages which are critical immunomodulatory cells. I have shown that H. pylori can trigger apoptosis of macrophages and have identified the bacterial virulence factors that are involved in this process. I have also identified a unique compartment in which H. pylori resides within macrophages to promote its own survival thus providing a possible explanation for persistence of the bacteria and the development of chronic infection. The characterization of this unique compartment in both gastric epithelial cells and macrophages and its role in disease is the focus of ongoing research.

Overall, these results enhance our understanding of how H. pylori evades immune responses to cause disease and also provide a basis for the development of novel strategies to treat this chronic infection.

External Funding

• Cell signals: cell signaling in mucosal inflammation and pain. Richard Ellen, Nicola Jones: Canadian Institutes of Health Research. 2002 – 2005.
• Molecular mechanisms associated with H. pylori survival in macrophages.
• Jones NL: Canadian Assocation of Gastroenterology / CIHR / Rx&D. 2004 - 2006
• Host immune response to Helicobacter pylori infection. Jones NL: Canadian Institute of Health Research . 2004 - 2007

Achievements

• University of Toronto Department of Paediatrics Junior Faculty Research Award 2004
• University of Toronto Department of Physiology Excellence in Teaching Award 2003
• World Congress of Pediatric Gastroenterology/ Nutrition Young Investigator Award. 2000

Publications

Bronte-Tinkew DM, Terebiznik M, Franco A, Ang M, Ahn D, Mimuro H, Sasakawa C, Ropeleski MJ, Peek Jr RM, Jones NL: Helicobacter pylori cytotoxin-associated gene A activates the signal transducer and activator of transcription 3 pathway in vitro and in vivo. Cancer Res., 2009: 69 (2).

Hussey S, Terebiznik MR, Jones NL: Autophagy: healthy eating and self digestion for gastroenterologists. J. Pediatr. Gastroenterol. Nutr., 2008: 46: 496-506.

Terebiznik MR, Vazquez CL, Banks D, Colombo MI, Jones NL: Helicobacter pylori VacA toxin promotes bacterial intracellular survival in gastric epithelial cells. Infect. Immun., 2006: 74: 12: 6599-614.

Avitzur Y, Galindo-Mata E, Jones NL: Oral vaccination against Helicobacter pylori infection is not effective in mice with Fas ligand deficiency. Dig. Dis. Sci., 2005: 50: 2300-6.

Johnson-Henry KC, Nadjafi M, Avitzur Y, Ngan B, Mitchell DJ, Galindo-Mata E, Jones NL, Sherman PM: Amelioration of the effects of Citrobacter rodentium infection in mice by pretreatment with probiotics. J. Infect. Dis., 2005: 191: 2106-17.

Menaker R, Ceponis P, Jones NL: Helicobacter pylori induces apoptosis of macrophages via the mitochondrial pathway. Infect. Immun., 2004: 72: 2889-98.

Mitchell D, Huynh H, Ceponis P, Jones NL, Sherman P: Helicobacter pylori disrupts signal transducer and activator of transcription (STAT) 1 signaling in vitro. Infect. Immun., 2004: 72: 537-45.

Ceponis PJM, McKay DM, Galindo-Mata E, Jones NL: Helicobacter pylori infection interferes with epithelial STAT6-mediated interleukin-4 signal transduction independent of cagA, cagE, or vacA. J. Immunol., 2003: 171: 2035-41.

Zheng PY, Jones NL: Helicobacter pylori trains expressing the vacuolating cytotoxin interrupt phagosome maturation in macrophages by recruiting and retaining TACO (coronin). Cell. Microbiol., 2003: 5: 1: 25-40.

Jones NL, Day AS, Galindo-Mata E, Jennings H, Shannon P, Sherman P: Enhanced disease severity in Helicobacter pylori-infected mice deficient in Fas signaling. Infect. Immun., 2002: 70: 2591-7.

Invited Reviews & Book Chapters

Wine E, Terebiznik MR, Jones N: Microbial interactions with gut epithelium. Pediatric Gastrointestinal Disease: Physiology, Diagnosis, Management, 5th Edition, [Kleinman, Goulet, Mieli-Vergani, Sanderson, Sherman, Shneider (Editors)], BC Decker Inc., Hamilton, ON, 2008: 1: 373-90.

Jones NL, Sherman PM:  Microbial interactions with gut epithelium. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 4th Edition [Walker, Goulet, Kleinman, Sherman, Shneider, Sanderson (Editors)], BC Decker Inc., Hamilton, ON, 2004: 21-34.

Jones NL: Detection of Shiga toxin-mediated programmed cell death and delineation of death signaling pathways. Methods in Molecular Medicine, 2003: 73: 229-41.

Jones NL, Perdue M, Sherman P, McKay D: Epithelial microbial interactions. Methods in Molecular Biology: Epithelial Cell Culture Protocols [Wise (Editor)], Humana Press Inc., Totowa, NJ, 2002: 188: 383-400.