Dr. Mike Risbano’s Research
Dr. Risbano’s research interests are in the discovery and implementation of biomarkers for the early diagnosis of pulmonary hypertension in patients with scleroderma (SSc-PAH). He is interested in the hemodynamic evaluation of subjects with pulmonary hypertension and correlation of hemodynamic values with biomarker levels. Dr. Risbano also has a research interest in the hemodynamic responses to vasoactive medications.
Dr. Risbano’s interest in biomarker discovery is illustrated in his CTS 2010 publication. This project utilized microarray analysis of peripheral blood mononuclear cells as an initial step to identify novel biomarkers related to inflammation and autoimmunity in SSc-PAH. Figure 1 (below) is an excerpt from the CTS 2010 publication of (a) an unsupervised dendrogram and heat map and (b) a supervised principal component analysis. The unsupervised hierarchical clustering was performed using the 17,412 probesets. The red boxes below the dendrogram indicate SSc without PAH, blue boxes indicate SSc-PAH. In the heat map below, blue and red colors indicate relatively low and high transcript expression respectively. The supervised principal component analysis of the Microarray Cohort, SSc without PAH (n=10, red) and SSc-PAH (n=10, blue), shows that at a p<0.0001, 459 genes were differentially expressed between the two groups.
Figure 2 (below) is a confirmation of selected biomarkers from the microarray analysis in figure 1 by RT-qPCR. Relative expression of SSc-PAH vs. SSc without PAH was significantly different for all 5 selected genes in the Microarray Cohort. In a second, separate Validation Cohort of SSc-PAH (n=15) vs. SSc without PAH (n=19) 4 genes were significantly different by RT-qPCR. TGFBR2 was not validated in this cohort, but approached statistical significance (data not shown).
In order to further investigate the biomarkers identified by the microarray analysis, flow cytometry was utilized to evaluate IL-7R on the protein level. Figure 3 (below) shows the results of flow cytometry of CD4+ cells for IL-7R expression. Figure 3a shows that the expression of IL-7R on CD4+ cells is decreased in scleroderma patients with PAH compared to SSc without PAH. Figure 3b is a representative histogram of IL-7R mean fluorescence intensity (MFI) on CD4+ T cells from subjects with SSc, with and without PAH. Figure 3c shows a comparison of IL-7R MFI on CD4+ T cells from subjects with SSc, with and without PAH.
Dr. Risbano is also interested in investigating the biomarker GDF-15 in pulmonary hypertension.