Biomarkers Platform

Dr. Don Sin

Platform Leader: Dr. Don Sin

 

 

 

 

 

 

 

Goals

  • To determine novel molecular targets of airway disease as a foundation for biomarker discovery.
  • To use emerging genomics and proteomics tools to better phenotype cohorts and to develop novel biomarkers to predict development and progression of chronic airway diseases.

Publications

Studart Leitao FS, Hang Chen H, Ngan DA, Tam A, Kirby M, Sin DD. Current methods to diagnose small airway disease in paients with COPD. Expert Review of Respiratory Medicine (in press).

Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Fishbane N, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Leung JM, Man SF, Aaron SD, Reed RM, Sin DD. Serum immunoglobulin G and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease. Journal of Allergy and Clinical Immunology (in press).

Chen W, FitzGerald JM, Sin DD, Sadatsafavi M. Excess economic burden of comorbidities in COPD: a 15-year population-based study. European Respiratory Journal (in press).

Khakban A, Sin DD, FitzGerald JM, McManus B, Ng R, Hollander Z, Sadatsafavi M. The projected epidemic of COPD hospitalizations over the next 15 Years: a population based perspective. American Journal of Respiratory and Critical Care Medicine 2017;195:287-91.

Kirby M, Eddy RL, Pike D, Svenningsen S, Coxson HO, Sin DD, McCormack DG, Parraga G; Canadian Respiratory Research Network. MRI ventilation abnormalities predict quality of life and lung function changes in mild-to-moderate COPD: longitudinal TINCan Study. Thorax 2017;72:475-77.

Obeidat M, Nie Y, Chen V, Shannon CP, Andiappan AK, Lee B, Rotzschke O, Castaldi PJ, Hersh CP, Fishbane N, Ng RT, McManus B, Miller BE, Rennard S, Paré PD, Sin DD. Network-based analysis reveals novel gene signatures in peripheral blood of patients with chronic obstructive pulmonary disease. Respiratory Research 2017;18:72.

Chen YR, Chen V, Hollander Z, Leipsic JA, Hague CJ, DeMarco ML, FitzGerald JM, McManus BM, Ng RT, Sin DD. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations. PloS One 2017;12:e0174063.

Obeidat M, Nie Y, Chen V, Shannon CP, Andiappan AK, Lee B, Rotzschke O, Castaldi PJ, Hersh CP, Fishbane N, Ng RT, McManus B, Miller BE, Rennard S, Paré PD, Sin DD. Network-based analysis reveals novel gene signatures in peripheral blood of patients with chronic obstructive pulmonary disease. Respiratory Research 2017;18(1):72.

Hollander Z, DeMarco ML, Sadatsafavi M, McManus BM, Ng RT, Sin DD. Biomarker Development in COPD: moving p-values to products to impact patient care. Chest 2017;151(2):455-67.

Aaron SD, Tan W, Bourbeau J, Sin DD, Loves RH, MacNeil J, Whitmore GA. Diagnostic instability and reversals of COPD diagnosis in subjects with mild to moderate airflow obstruction. American Journal of Respiratory and Critical Care Medicine 2017;196:30.

Ra SW, Sze MA, Lee EC, Tam S, Oh Y, Fishbane N, Criner GJ, Woodruff PG, Lazarus SC, Albert R, Connett JE, Han MK, Martinez FJ, Aaron SD, Reed RM, Man SF, Sin DD. Azithromycin and risk of COPD exacerbations in patients with and without Helicobacter pylori. Respiratory Research 2017;18:109

Obeidat M, Nie Y, Fishbane N, Li X, Bossé Y, Joubert P, Nickle DC, Hao K, Postma DS, Timens W, Sze MA, Shannon CP, Hollander Z, Ng RT, McManus B, Miller BE, Rennard S, Spira A, Hackett TL, Lam W, Lam S, Faner R, Agusti A, Hogg JC, Sin DD, Paré PD. Integrative genomics of emphysema associated genes reveals potential disease biomarkers. Am J Respir Cell Mol Biol. 2017 May 1 (in press)

Shannon CP, Balshaw R, Chen V, Hollander Z, Toma M, McManus BM, FitzGerald JM, Sin DD, Ng RT, Tebbutt SJ. Enumerated –a R package to estimate the cellular composition of whole blood from Affymetrix Gene ST gene expression profiles. BMC Genomics. 2017 Jan 6;18(1):43

Shannon CP, Chen V, Takhar M, Hollander Z, Balshaw R, McManus BM, Tebbutt SJ, Sin DD, Ng RT. SABRE: a method for assessing the stability of gene modules in complex tissue and subject populations. BMC Bioinformatics. 2016;17:460.

Obeidat M, Ding X, Fishbane N, Hollander Z, Ng RT, McManus B, Tebbutt SJ, Miller BE, Rennard S, Pare PD, Sin DD. The effect of different case definitions of current smoking status on the discovery of smoking-related blood gene expression signatures in chronic obstructive pulmonary disease. Nicotine and Tobacco Research 2016;18:1903-9.

Tkacova R, Dai DLY, Vok JM, Leung J, Hiemstra PS, van den Berge M, Kunz L, Hollander Z, Tashkin D, Wise R, Connett JE, Ng R, McManus BM, Man SFP, Postma DS, Sin DD. Airway hyperresponsiveness in COPD: a marker of asthma-COPD overlap syndrome? Journal of Allergy and Clinical Immunology 2016;138:1571-9.

Zafari Z, Sin DD, Postma DS, Löfdahl CG, Vonk J, Bryan S, Lam S, Tammemagi CM, Khakban R, Man SF, Tashkin D, Wise RA, Connett JE, McManus B, Ng R, Hollander Z, Sadatsafavi M. Individualized prediction of lung-function decline in chronic obstructive pulmonary disease. CMAJ 2016;188:1004-11.

Leung JM, Chen V, Hollander Z, Dai D, Tebbutt SJ, Aaron SD, Vandemheen KL, Rennard SI, FitzGerald JM, Woodruff PG, Lazarus SC, Connett JE, Coxson HO, Miller B, Borchers C, McManus BM, Ng RT, Sin DD. COPD exacerbation biomarkers validated using multiple reaction monitoring mass spectrometry. Plos One 2016;11:e0161129.

Labonté LE, Tan WC, Li PZ, Mancino P, Aaron SD, Benedetti A, Chapman KR, Cowie R, FitzGerald JM, Hernandez P, Maltais F, Marciniuk DD, O'Donnell D, Sin DD, Bourbeau J; Canadian Respiratory Research Network and the CanCOLD Collaborative Research group. Undiagnosed COPD contributes to the burden of health care utilization: data from the CanCOLD Study. American Journal of Respiratory and Critical Care Medicine 2016;194:285-98.

Spanjer AI, Menzen MH, Dijkstra AE, van den Berge M, Boezen HM, Nickle DC, Sin DD, Bossé Y, Brandsma CA, Timens W, Postma DS, Meurs H, Heijink IH, Gosens R. A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis. Thorax 2016;71:312-22 2014 IF: 8.290

Chen YW, Leung JM, Sin DD. A systematic review of diagnostic biomarkers of COPD exacerbation. PloS One 2016;11:e0158843.

Biagioni BJ, Tam S, Chen YR, Sin DD, Carlsten C. Effect of controlled human exposure to diesel exhaust and allergen on airway surfactant protein D, myeloperoxidase and club (Clara) cell secretory protein 16. Clinical Experimental Allergy 2016;46:1206-13.

Khakban A, Sin DD, FitzGerald JM, Ng R, Zafari Z, McManus B, Hollander Z, Marra C, Sadatsafavi M. 10 year trend in direct costs of COPD: a population based study. Chest 2015;148:640-6. 2014 IF: 7.483

Obeidat M, Fishbane N, Nie Y, Chen V, Hollander Z, Tebutt SJ, Bosse Y, Ng RT, Miller BE, McManus B, Rennard SI, Pare PD, Sin DD. The effect of statins on gene expression in COPD. PloS One 2015;10:e0140022 2014 IF: 3.234

Lane J, van Eeden SF, Obeidat M, Sin DD, Tebbutt SJ, Timens W, Postma DS, Laviolette M, Paré PD, Bossé Y. Impact of statins on gene expression in human lung tissues. PLoS One 2015;10:e0142037 2014 IF: 3.234

Minelli C, Dean CH, Hind M, Alves AC, Amaral AF, Siroux V, Huikari V, Soler Artigas M, Evans DM, Loth DW, Bossé Y, Postma DS, Sin DD, Thompson J, Demenais F, Henderson J; SpiroMeta consortium; CHARGE consortium, Bouzigon E, Jarvis D, Järvelin MR, Burney P. Association of forced vital capacity with the developmental gene NCOR2. PloS One (in press) 2014 IF: 3.234

Should COPD stand for “Comorbidities-related Obstructive Pulmonary Disease”?
Sin DD. Should COPD stand for “Comorbidities-related Obstructive Pulmonary Disease”? European Respiratory Journal 2015;46:901-2.

Molecular mechanisms underlying variations in lung function: a systems genetics analysis
Obeidat M, Hao K, Bossé Y, Nickle DC, Nie Y, Postma DS, Laviolette M, Sandford AJ, Daley DD, Hogg JC, Elliott WM, Fishbane N, Timens W, Hysi PG, Kaprio J, Wilson JF, Hui J, Rawal R, Schulz H, Stubbe B, Hayward C, Polasek O, Järvelin MR, Zhao JH, Jarvis D, Kähönen M, Franceschini N, North KE, Loth DW, Brusselle GG, Smith AV, Gudnason V, Bartz TM, Wilk JB, O'Connor GT, Cassano PA, Tang W, Wain LV, Artigas MS, Gharib SA, Strachan DP, Sin DD, Tobin MD, London SJ, Hall IP, Paré PD. Molecular mechanisms underlying variations in lung function: a systems genetics analysis. Lancet Respiratory Medicine 2015;3:782-95

The relationship between helicobacteri pylori seropositivity and chronic obstructive pulmonary
Sze MA, Chen YR, Tam S, Tashkin D, Wise RA, Connett JE, Man SFP, Sin DD. The relationship between helicobacteri pylori seropositivity and chronic obstructive pulmonary disease. Thorax 2015;70:923-9.

Serum bilirubin and disease progression in mild chronic obstructive pulmonary disease
Apperley S, Park HY, Holmes DT, Man SFP, Tashkin D, Wise RA, Connett JE, Sin DD. Serum bilirubin and disease progression in mild chronic obstructive pulmonary disease. Chest  2015;148:169-75

Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease
Liu JC, Leung JM, Ngan DA, Nashta NF, Guillemi S, Harris M, Lima VD, Um SJ, Li Y, Tam S, Shaipanich T, Raju R, Hague C, Leipsic JA, Bourbeau J, Tan WC, Harrigan PR, Sin DD, Montaner J, Man SFP. Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease. Plos One 2015;10:e0124426.