Jorge Moscat's Research Focus
The signaling pathways that regulate inflammation and cell proliferation, and their interface with metabolism, are central in the control of tumor initiation and progression as well as in the development of metastasis. The study of these fundamental biological questions results in the identification of non-oncogenic and oncogenic vulnerabilities that will lead to the design of more efficacious and less toxic anti-cancer therapies.
Jorge Moscat's Research Report
We are interested in the study of these pathways in the context of the role and mechanism of action of a number of key signaling molecules, which include the autophagy and signaling adapters p62 and NBR1, and the kinases MEKK3, PKCζ and PKCλ/ι. All contain PB1 protein-protein interaction domains that confer selectivity to their mechanism of action, and make them attractive targets in cancer. My laboratory discovered p62 (Sanchez et al., MCB 18, 3069, 1998), which along with NBR1 are two proposed chaperones in autophagy, and we showed that both play critical roles as signaling adaptors in inflammation, metabolism and cancer. We were pioneers in the field and have demonstrated that p62 is a central molecule in cancer, beyond its role as autophagy substrate and adaptor. Studies ongoing in my laboratory are aimed at understanding how these signaling adaptors regulate the complex series of interactions in the tumor microenvironment, specially the cross-talk between the tumor epithelium and the stroma, in several types of cancers including pancreatic, liver and intestinal.
Likewise, we were the first to address the role of PKCζ in cell signaling (Berra et al., Cell 74, 555, 1993; Diaz-Meco et al., Cell 86, 777, 1996; Leitges et al., Mol. Cell 8, 771, 2001). Later, we were the first to demonstrate that, contrarily to previous assumptions based on cell lines and transfection experiments, PKCζ is a novel tumor suppressor and negative regulator of inflammation, metabolic reprograming, and stemness. More recent studies in our laboratory are focused on the signaling cross-talk between stem cells and Paneth cells in the intestinal niche, and how PKCζ and PKCλ/ι regulate intestinal cancer initiation in the context of the effect of inflammation and the microbiome. Our studies address these complex processes, and their underlying signaling pathways, by using physiologically relevant mouse models of colon cancer, and the interrogation of human samples. Specifically, this approach guarantees the importance of our findings and their potential impact in human disease.
Jorge Moscat's Bio
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 SBP faculty in 2011.
1984: Ph.D., Universidad Complutense, Madrid, Biochemistry and Molecular Biology
1980: B.S., Universidad Complutense, Madrid, Biochemistry
Member of Editorial Boards
Honors and recognitions
Member of the Editorial Board of Molecular and Cellular Biology
2006: Elected Member of the Academia Europaea
2002: Member of the Editorial Board of EMBO Journal
2002: Member of the Editorial Board of EMBO Reports
2001: Award of the Juan March Foundation
2000: Award of the Carmen and Severo Ochoa Foundation
1999: Award of the Spanish Royal Academy of Sciences
1998: Award of the Foundation for Health Sciences
1995: Elected member of the European Molecular Biology Organization (EMBO)
1989 & 1991: Awards of the Spanish Cancer Scientific Association
Ma L, Tao Y, Duran A, Llado V, Galvez A, Barger JF, Castilla EA, Chen J, Yajima T, Porollo A, Medvedovic M, Brill LM, Plas DR, Riedl SJ, Leitges M, Diaz-Meco MT, Richardson AD, Moscat J
Cell 2013 Jan 31 ;152(3):599-611
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.
Valencia T, Kim JY, Abu-Baker S, Moscat-Pardos J, Ahn CS, Reina-Campos M, Duran A, Castilla EA, Metallo CM, Diaz-Meco MT, Moscat J
Cancer Cell 2014 Jul 14 ;26(1):121-135
Moscat J, Karin M, Diaz-Meco MT
Cell 2016 Oct 20 ;167(3):606-609
Reina-Campos M, Diaz-Meco MT, Moscat J
Cancer Cell 2019 Aug 14 ;
Increased Serine and One-Carbon Pathway Metabolism by PKCλ/ι Deficiency Promotes Neuroendocrine Prostate Cancer.
Reina-Campos M, Linares JF, Duran A, Cordes T, L'Hermitte A, Badur MG, Bhangoo MS, Thorson PK, Richards A, Rooslid T, Garcia-Olmo DC, Nam-Cha SY, Salinas-Sanchez AS, Eng K, Beltran H, Scott DA, Metallo CM, Moscat J, Diaz-Meco MT
Cancer Cell 2019 Mar 18 ;35(3):385-400.e9
The signaling axis atypical protein kinase C λ/ι-Satb2 mediates leukemic transformation of B-cell progenitors.
Nayak RC, Hegde S, Althoff MJ, Wellendorf AM, Mohmoud F, Perentesis J, Reina-Campos M, Reynaud D, Zheng Y, Diaz-Meco MT, Moscat J, Cancelas JA
Nat Commun 2019 Jan 4 ;10(1):46
p62/SQSTM1 Fuels Melanoma Progression by Opposing mRNA Decay of a Selective Set of Pro-metastatic Factors.
Karras P, Riveiro-Falkenbach E, Cañón E, Tejedo C, Calvo TG, Martínez-Herranz R, Alonso-Curbelo D, Cifdaloz M, Perez-Guijarro E, Gómez-López G, Ximenez-Embun P, Muñoz J, Megias D, Olmeda D, Moscat J, Ortiz-Romero PL, Rodríguez-Peralto JL, Soengas MS
Cancer Cell 2019 Jan 14 ;35(1):46-63.e10
Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance.
Nakanishi Y, Duran A, L'Hermitte A, Shelton PM, Nakanishi N, Reina-Campos M, Huang J, Soldevila F, Baaten BJG, Tauriello DVF, Castilla EA, Bhangoo MS, Bao F, Sigal D, Diaz-Meco MT, Moscat J
Immunity 2018 Dec 18 ;49(6):1132-1147.e7
Zhang Y, Mun SR, Linares JF, Ahn J, Towers CG, Ji CH, Fitzwalter BE, Holden MR, Mi W, Shi X, Moscat J, Thorburn A, Diaz-Meco MT, Kwon YT, Kutateladze TG
Nat Commun 2018 Oct 22 ;9(1):4373