The Goukassian Laboratory is a part of the GeneSys Research Institute GRI with academic affiliation to Tufts University School of Medicine TUSM, located at the Center of Biomedical Research on the Steward St Elizabeth’s Medical Center of Boston Campus.
The lab focuses on six areas in basic, translational and clinical research. (Basic) Cardiovascular space radiobiology, stem and progenitor cell biology, therapeutic angiogenesis. (Translational) Pathological angiogenesis and novel cancer therapeutics. (Clinical) Robotic-assisted percutaneous coronary intervention and effects of cancer radiotherapy on development of premature coronary artery disease and vasculopathy.
I. Mending the Post-Ischemic Recovery
(A and B) Microscopic morphologic changes that evolve over time after AMI. Evolution of microscopic morphologic changes after AMI: within first 24 h – myocardial fibers become wavy, edema, hemorrhage, coagulation necrosis, and early neutrophilic infiltrate develops; 2–4 days – loss of nuclei, microscopic necrosis, heavy neutrophilic infiltrate, and dilation of vessels develops; 5–14 days – macrophage and mononuclear infiltration and fibrovascular responses begin followed by prominent granulation; 2–10 days – fibrosis with scarring develops.
(C) Hypothetical effect of modulation of TNF receptor expression on AMI recovery outcome. Inhibition of p55 receptor in first hours and days after AMI may decrease ischemia-induced acute inflammation and myocardial tissue damage, whereas p75 receptor over-expression within days and weeks after AMI may enhance collateral vessel development and myocardial regeneration
II. New Paradigm in Cancer Therapeutics
(A), Biological processes in WT cells in the presence of LOW TNF concentration
(B), Hypothetical diagram of the biological processes in TNFR2/p75 tumor cells in the presence of LOW or HIGH TNF concentrations shows that inhibition of TNFR2/p75 expression or signaling should have multifaceted anti-tumor effects irrespective of lower or higher doses of TNF.
III. Inhibition of Radiation-induced Non-targeted Effects in Bone Marrow Endothelial Progenitor Cells
Neutralization of TNF-α in gamma-irradiated conditioned media inhibits p-H2AX foci formation, a marker for DNA double starnd breaks, in TNFR1/p55KO and WT EPCs ex-vivo.
Media transfer experiments were performed in N-IR BM-derived EPCs from both WT and TNFR1/p55KO mice, where in the IR-CM at respective time points were filtered and then incubated in TNF-α neutralizing antibody before transferring on to respective naïve N-IR BM-EPCs.
Graphic representation of mean p-H2AX foci/cell post 24 h treatment of naïve WT and p55KO with IR-CM medium collected and treated with TNF-α neutralizing antibody from respective WT and p55KO EPCs at 1 h, 5 h, 24 h, Day 3 and Day 5 post 1 Gy γ-IR. Treatment of IR-CM with TNF neutralizing antibody decreased the formation of p-H2AX foci at all time point examined in both WT and p55KO EPCs. However, the most significant decreases for WT EPCs were observed at 5, 24 hours and 3 days and for p55KO EPCs at 1, 5 hours, and 3, 5 days. These findings indicate that inhibition of TNF-a may represent a therapeutic modality for the prevention of early and intermediate radiobiological bystander responses in WT tissue.