Pedro Geraldes, PhD
Assistant Professor of Medicine
Pedro Geraldes was trained in Biochemistry at the University of
Montreal where he obtained a PhD degree. He studied the role of hormone receptors
during vascular healing after percutaneous coronary intervention under the supervision
of Dr J.-F. Tanguay. He then joined the laboratory of Prof. George L. King at Joslin
Diabetes Center in Boston, where he worked as a post-doctoral fellow on PKC actions
and vascular complications such as retinopathy, nephropathy and atherosclerosis. He
recently joined the Department of Medicine at the University of Sherbrooke as an
Click here for pdf CV
Selected Scientific Contributions
Diabetic patients are prone to increase macrovascular diseases such
as atherosclerosis and microvascular complications such as neuropathy, nephropathy and
retinopathy. Metabolite abnormalities induced by the lack of insulin, such as
hyperglycemia and dyslipidemia, are believed to be the major risk factors for their
development. However, much less studied is the importance of the response of local
vascular tissues to the elevated levels of systemic glucose and lipid-induced toxic
factors. For example, several clinical observations showed that the expression of
VEGF is increased in the retina and kidney but decreased in the myocardium of diabetic
animals and patients. These clinical results strongly supported the notion that
vascular tissue react differently to adverse effects of hyperglycemia and other
systemic toxic factors induced by diabetes. Identification of new mechanisms causing
chronic vascular damage is still a challenge for on-going research on diabetic
complications. Dr Geraldes recently demonstrated that the expression of SHP-1, a
protein tyrosine phosphatase (PTP) that is critical in de-activating PDGF action, is
elevated by diabetes and hyperglycemia in the retina, kidney and ischemic muscles.
Increase expression of SHP-1 may cause vascular complication in the kidney
(epithelial and endothelial cell death and dysfunction) and reduce collateral vessel
formation during ischemia (diminution of oxygen to the tissue). The research projects
of Dr Geraldes are related to study the mechanisms underlying hyperglycemia and
lipid-induced protein kinase C (PKC) activation in the abnormalities of growth factor
actions such as PDGF, VEGF, angiopoietin and insulin related to kidney, peripheral
vessels and atherosclerotic plaque formation. Thus, finding new cellular targets
involved in growth factor resistance and which are activated downstream by various
toxic metabolites of glucose and lipids is crucial to identifying early markers of
vascular diseases and new therapeutic targets in order to improve even reverse
vascular complications of diabetic patients
Click here for PubMed listing
Current projects in the laboratory:
Inhibition of survival factors in diabetic nephropathy.
Understanding how hyperglycemia-induced toxic metabolites that will contribute to
podocyte and renal endothelial cell apoptosis and dysfunction leading to diabetic
nephropathy. We are studying the mechanisms related to growth factor (VEGF, Angiopoietin)
disorder and signaling pathway induced by angiotensin, glucose and lipid metabolism.
Mechanism for poor collateral vessel formation in diabetes.
We are investigating the role of protein tyrosine phosphatase induced by hyperglycemia
causing inhibition of growth factors actions (PDGF, VEGF, insulin) and poor collateral
vessel formation during ischemia.
Protein kinase C and atherosclerotic plaque formation.
The goal is to identify new target genes and potential markers regulated by protein
kinase C activation and lipid metabolism involved in the atherosclerotic plaque
formation in diabetes.
Our laboratory investigates these multiple factorial complications
of the vessels using sophisticated animal models (Cre-lox/Tet-ON system) for tissue
specific knock-down and the most recent molecular and cellular technologies including
gene silencing (siRNA, shRNA), laser capture microscopy, biochemical and cellular assays.