Sanford-Burnham is the ideal place to carry out highly collaborative interdisciplinary research on cutting-edge biology questions with impact in the discovery of new therapeutic targets for human diseases.
Dr. Moscat studies the control of cancer metabolism and inflammation.
Dr. Moscat completed his Ph.D., Universidad Complutense, Madrid, Biochemistry and Molecular Biology.
Jorge Moscat's Research Focus
Cancer, Metabolic Diseases
Our laboratory has a long-standing interest in the control of stress in cancer cells. Specifically, how tumors respond to situations of nutrient deprivation or to the existence of a pro-inflammatory and nutrient-rich environment is critical for cancer progression. A key finding from our group is that the genetic ablation of the signaling adapter and autophagy substrate p62 in mice leads to obesity, suggesting a role of p62 in the control of the differentiation of fat cells (also known as adipogenesis). Interestingly, p62 is also overexpressed in a myriad of tumors suggesting an additional role in cancer initiation and/or progression. In fact, the ablation of p62 in tumor epithelia results in inhibited proliferation and survival through at least two essential mechanisms: NF-κB and mTORC1. NF-κB regulates survival by detoxifying cancer cells of reactive oxygen species, whereas mTORC1 controls cell growth and proliferation. p62 is a fascinating molecule that is being targeted therapeutically in our laboratory with the aim of designing better anti-cancer drugs. In this regard, p62 interacts with key signaling intermediaries in several fundamental pathways such as TRAF6, PKCζ and PKCλ/ι, Raptor, or the NRF2 regulator, Keap1. Understanding how p62 orchestrates all these signals is of paramount importance for the identification of tumor-specific therapeutic targets.
Jorge Moscat's Research Report
Intratumoral nutrient stress has been found even in early-stage cancers, correlating with poor patient survival. Therefore, the investigation of the signaling mechanisms governing cancer cell proliferation under nutrient deprivation is of paramount importance for the identification of new and more selective therapeutic targets, and for a better understanding of the role of the tumor microenvironment in the response of cancer cells to nutrient shortage. We previously showed that the loss of PKCζ induced tumorigenesis in several endogenous mouse cancer models including lung (Ras), prostate (PTEN) and intestine (APC). Our more immediate goals are to explore a novel role for PKCζ and other components of its signaling cascade and family, such as PKCλ/ι, as a tumor suppressor that acts by controlling the interplay between tumor cells and the inflammatory microenvironment milieu. The long-term goal of our laboratory is to identify novel signaling networks that influence cell metabolism and allow cancer cells to proliferate under inflammatory and nutrient-scarce microenviromental conditions. We are actively studying how intestinal cancer stem cells respond to these challenging tumor microenvironment conditions. We are also investigating how the cross-talk between the tumor epithelium and the stroma in hepatocellular carcinoma determine the final outcome of malignant cells and their potential responses to nutrient-curtailing therapies.
About Jorge Moscat
Dr. Moscat earned a bachelor’s degree in chemistry and a doctorate in biochemistry/molecular biology at the Universidad Complutense in Madrid, Spain. He completed postgraduate studies with fellowships of the Spanish Education and Science Ministry and Juan March Foundation in Madrid and at the NIH. Dr. Moscat joined the University of Cincinnati in 2006 from the Center of Molecular Biology of the Spanish National Research Council in Madrid, where he conducted cancer cell biology research, focusing primarily on signaling pathways in cancer, obesity and inflammation. In 2008, he became professor and chairman of the Department of Cancer and Cell Biology at the University of Cincinnati College of Medicine and associate director of basic science for the Cincinnati Cancer Consortium. Dr. Moscat joined the Sanford-Burnham faculty in 2011.
Ph.D., Universidad Complutense, Madrid, Biochemistry and Molecular Biology, 1984
B.S., Universidad Complutense, Madrid, Biochemistry, 1980
Honors and Recognition
Elected Member of the Academia Europaea, 2006
Member of the Editorial Board of EMBO Journal, 2002
Member of the Editorial Board of EMBO Reports, 2002
Award of the Juan March Foundation, 2001
Award of the Carmen and Severo Ochoa Foundation, 2000
Award of the Spanish Royal Academy of Sciences, 1999
Award of the Foundation for Health Sciences, 1998
Elected member of the European Molecular Biology Organization (EMBO), 1995
Awards of the Spanish Cancer Scientific Association, 1989 &1991
Member of Editorial Boards