Pascal Goldschmidt, M.D.
Professor of Medicine
Description of Research
Dr. Goldschmidt’s cancer-related research suggests that aging of the immune system leads to reduced surveillance capacity for the elimination of cells that have undergone malignant transformation. Disruption or deficiency of repair mechanisms can lead to two very different types of chronic illnesses: (a) exhaustion of repair cells for atherosclerosis with its thromboembolic complications of acute myocardial infarction, sudden cardiac death, symptomatic coronary artery disease, stroke, and other symptomatic cerebral vascular disease; and (b) transformation of repair cells for cancer illnesses.
In conjunction with the Mesri lab, Dr. Goldschmidt discovered that the small GTP-binding protein Rac1, when constitutively activated and expressed in cells that also express smooth muscle cell-actin, can induce Kaposi sarcoma lesions in murine, a tumor triggered by the human herpesvirus 8 (HHV8) which is particularly high in patients infected with the human immunodeficiency virus (patients with AIDS). These lesions are identical to lesions found in human patients. A key gene for the development of Kaposi sarcoma is coded for by the HHV8 genome, vGPCR. vGPCR, when expressed on the surface of endothelial cells, is required for their transformation in Kaposi sarcoma cells and for the generation of Kaposi sarcoma in nude mice. Among the various targets of Rac1, which functions as a biologic timer for specific cellular activities, the most relevant is NADPH-oxidase and, in particular, the isoforms that bind Rac1 for activity. Dr. Goldschmidt has shown that Rac1 is an important regulator of mitogenic activity induced by oncogenic Ras in transformed fibroblasts. Thus, his data suggests the Kaposi progenitor is a common progenitor for endothelial cells and pericytes.
Most recently, Dr. Goldschmidt has shown that KSHV oncogenesis in the KSHV-infected tumor mouse model mECK36 is mediated by a c-sis/PDGF-BB-inducted Rac1 and ROS-mediated loop, leading to STAT3 transcriptional activation of c-Myc, VEGF, and KSHV latent viral gene expression. This oncogenic mechanism can be targeted with anti-oxidant NAC and PDGF receptor inhibitors to control KSHV tumorigenesis and Kaposi’s sarcoma.
In addition to his cancer research, Dr. Goldschmidt is an internationally-renowned board-certified cardiologist and visionary in cardiovascular sciences. He maintains an outstanding track record for excellence in both basic and clinical research in several areas including cell and molecular biology, vascular biology and redox signaling, and genetics. He is a pioneer and thought leader in genomic and molecular approaches to cardiovascular disease. His research applies epigenomics, genomics and cell therapy to prevention, diagnosis and treatment of coronary artery disease, which led to the discovery of a platelet receptor polymorphism that accounts for significantly increased risk of heart attacks. Dr. Goldschmidt has advanced our knowledge in the role of endothelial progenitor cells (EPCs) especially in their potential role in aging and arterial repair.
- Role of reactive oxygen species (ROS) in KSHV
- Description of ALDH as a novel EPC marker and role of EPC in pathologic angiogenesis and autoimmune disease
- Implication of a reactive oxygen species as a mediator of Ras-induced cell cycle progression independent of MAPK and JNK suggests a possible mechanism for the effects of antioxidants against Ras-induced cellular transformation
Selected Cancer-Related Publications
- Ma Q, Cavallin LE, Leung HJ, Chiozzini C, Goldschmidt-Clermont PJ, Mesri EA. A Role for Virally Induced Reactive Oxygen Species in Kaposi's Sarcoma Herpesvirus Tumorigenesis. Antioxid Redox Signal :,2012 Read more »
- Goldschmidt-Clermont PJ, Seo DM, Wang L, Beecham GW, Liu ZJ, Vazquez-Padron RI, Dong C, Hare JM, Kapiloff MS, Bishopric NH, Pericak-Vance M, Vance JM, Velazquez OC. Inflammation, stem cells and atherosclerosis genetics. Curr Opin Mol Ther 12:712-23, 2010. Read more »
Collaborating in the Multidisciplinary Research Program(s):