Nicole Barra

 

 


PhD Student

barrang@mcmaster.ca

BSc Life Sciences - Human Biology, Health and Disease Specialization, University of Toronto

905-525-9140 extension 22778

 

 

 


Emerging evidence over the last decade has defined obesity as a chronic low grade inflammatory condition, due to a dysregulation in the production of cytokines affecting the regulation of whole-body energy metabolism and the development of obesity.  Our lab is very interested in understanding how pro-inflammatory cytokines, such as Interleukin-15 (IL-15), may play a role in the development of obesity and its associated chronic conditions. The Ashkar lab has several projects investigating the role of IL-15 in regulating adipose tissue and cormorbidities associated with obesity, utilizing both in vitro and in vivo murine models. We have found that varying IL-15 expression impacts fat mass and obesity development. It is our ultimate goal that additional insights into IL-15 biology and its effects on adipose tissue regulation will contribute to novel therapeutic strategies for the treatment and prevention of obesity.


The alarming global rise in the prevalence of obesity and its contribution to the development of chronic diseases is a serious health concern. Recently, obesity has been described as a chronic low grade inflammatory condition, influenced by both adipose tissue and immune cells suggesting pro-inflammatory cytokines may play a role in its etiology. Intriguing research has recently emerged examining the role of intestinal microorganisms in energy homeostasis and obesity. Variations in gut bacterial diversity exists between obese and lean individuals, suggesting differences in digestion and absorption could be important factors in the pathogenesis of obesity.


We previously examined the effects of Interleukin-15 (IL-15) on adipose tissue and its association with obesity [1]. Although this cytokine is mainly known to activate immune cells such as Natural Killer (NK) cells [2], our data demonstrates over-expression of IL-15 results in a lean body condition, while lack of IL-15 results in a significant increase in weight gain. Treatment with IL-15 induces weight loss in obese mice placed on a high-fat diet independent of food intake. The presence of IL-15 also causes decreased lipid deposition upon differentiation of human adipose derived mesenchymal stem cells into adipocytes, suggesting IL-15 mediates these effects directly. Additionally, serum IL-15 is significantly lower in obese patients when compared to normal weight individuals, demonstrating an association with body fat mass. Also, since IL-15 is the main cytokine involved in NK cell development and function [2], it has yet to be determined if these cells play a role in IL-15 mediated weight loss in vivo.

[1] Barra, NG et al. Obesity, 2009. Dec 17:1-7.

[2] Lodolce, J. et al. Mol Immunol, 2002. 39(9):537-44.

Awards
2011-2012 Ontario Graduate Scholarship (OGS)

2011 McMaster University’s Department Graduate Travel Scholarship (DGTS), Department of Pathology and Molecular Medicine

2010 Canadian Obesity Network Travel Scholarship

August 2010 Canadian Obesity Network 5th Annual Obesity Summer Boot Camp Attendee Award

2010 McMaster University’s Faculty of Health Sciences Research Plenary Poster Award

 

2009, 2010 McMaster University’s Faculty of Health Sciences Research Day Poster Award

Publications
Stephenson KB, Barra NG, Davies E, Ashkar A, and Lichty BD. “Expressing human Interleukin-15 from oncolytic VSV improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity.” 2011. Cancer Gene Therapy Epub Dec 9.

Abdul-Careem MF, Mian FM, Gillgrass A, Chenoweth MJ, Barra NG, Chan T, Al-Garawi AA, Chew MV, Yue G, and Ashkar AA. 2011. "FimH, a TLR4 ligand, induces innate antiviral responses in the lung leading to protection against lethal influenza infection in mice" Antiviral Res Nov 92(2):346-55.

Barra NG, Chew MV, Holloway AC, and Ashkar AA. 2011. “Interleukin-15 treatment improves glucose homeostasis and insulin sensitivity in obese mice.” Diabetes, Obesity, and Metabolism Epub Sept 9

Chan T, Barra NG, Lee A, and Ashkar, AA. 2011. “Innate and Adaptive Immunity against Herpes Simplex Virus Type 2 in the Genital Mucosa.” Journal of Reproductive Immunology Mar 88(2):210-8.

Barra NG, Gillgrass A, and Ashkar, AA. 2010. “Effective control of viral infections by the adaptive immune system requires assistance from innate immunity.” Expert Review of Vaccines Oct 9(10):1143-7.

Barra NG, Reid S, Mackenzie R, Werstuck G, Holloway AC, Trigatti B, Richards C, and Ashkar, AA. 2010. “Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes” Obesity (Silver Spring), Aug 18(8): 1601-7.