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The focus of the Diaz-Meco laboratory is the study of the molecular and cellular mechanisms that control tumor initiation and progression, and therapy resistance, with a particular interest in the control of lineage plasticity in prostate cancer. The approach of this laboratory is to identify metabolic and epigenetic vulnerabilities that will serve as therapeutic targets for new anti-cancer medicines that would selectively impact the growth and survival of the tumor cell, irrespective of its oncogenic load. The Diaz-Meco lab has recently identified the metabolic pathways underlying the acquisition of therapy-resistance in patients of the most aggressive form of metastatic prostate cancer. These studies unraveled potential therapeutic targets in the control of the metabolic and epigenetic programs whose therapeutic manipulation could restore sensitivity to androgen-deprivation therapy to patients that have become refractory to this type of treatment. The laboratory also studies the metabolic impact that reprogramming of the stroma has on prostate cancer cells and how that crosstalk is regulated during tumor initiation and progression.
Weill Cornell Medicine published Newsroom article on our research. Read it here!
Maria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
The complexity of the serine glycine one-carbon pathway in cancer.
J Cell Biol. 2020 Jan 6;219(1).
Reina-Campos M, Diaz-Meco MT, Moscat J.
PMID: 31690618
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
The Dual Roles of the Atypical Protein Kinase Cs in Cancer
Cancer Cell. 2019 Sep 16;36(3):218-235.
Reina-Campos M, Diaz-Meco MT, Moscat J.
PMID: 31474570; PMCID: PMC6751000
Read MoreMaria Diaz-Meco Conde, PhD
Increased Serine and One-Carbon Pathway Metabolism by PKCλ/ι Deficiency Promotes Neuroendocrine Prostate Cancer.
Cancer Cell. 2019 Mar 18;35(3):385-400.
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.
PMID: 30827887; PMCID: PMC6424636
Read MoreMaria Diaz-Meco Conde, PhD
Metabolic reprogramming of the tumor microenvironment by p62 and its partners
Biochim Biophys Acta Rev Cancer. 2018 Aug;1870(1):88-95.
Reina-Campos M, Shelton PM, Diaz-Meco MT, Moscat J.
PMID: 29702207; PMCID: PMC6193563
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor
Cancer Cell. 2018 Apr 9;33(4):770-784.
Huang J, Duran A, Reina-Campos M, Valencia T, Castilla EA, Müller TD, Tschöp MH, Moscat J, Diaz-Meco MT.
PMID: 29634950; PMCID: PMC5896786
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma
Cell Metab. 2017 Dec 5;26(6):817-829.
Linares JF, Cordes T, Duran A, Reina-Campos M, Valencia T, Ahn CS, Castilla EA, Moscat J, Metallo CM, Diaz-Meco MT.
PMID: 28988820; PMCID: PMC5718961
Read MoreMaria Diaz-Meco Conde, PhD
Metabolism shapes the tumor microenvironment
Curr Opin Cell Biol. 2017 Oct;48:47-53.
Reina-Campos M, Moscat J, Diaz-Meco M.
PMID: 28605656; PMCID: PMC5650101
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer
Cancer Cell. 2016 Oct 10;30(4):595-609.
Duran A, Hernandez ED, Reina-Campos M, Castilla EA, Subramaniam S, Raghunandan S, Roberts LR, Kisseleva T, Karin M, Diaz-Meco MT, Moscat J.
PMID: 27728806; PMCID: PMC5081228
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
p62 in Cancer: Signaling Adaptor Beyond Autophagy
Cell. 2016 Oct 20;167(3):606-609.
Moscat J, Karin M, Diaz-Meco MT.
PMID: 27768885; PMCID: PMC5114003
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells
Cancer Cell. 2016 Jun 13;29(6):935-948.
Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M.
PMID: 27211490; PMCID: PMC4907799
Read MoreMaria Diaz-Meco Conde, PhD
Amino Acid Activation of mTORC1 by a PB1-Domain-Driven Kinase Complex Cascade
Cell Rep. 2015 Aug 25;12(8):1339-52.
Linares JF, Duran A, Reina-Campos M, Aza-Blanc P, Campos A, Moscat J, Diaz-Meco MT.
PMID: 26279575; PMCID: PMC4551582
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis
Cancer Cell. 2014 Jul 14;26(1):121-135.
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.
PMID: 25002027; PMCID: PMC4101061
Read MoreMaria Diaz-Meco Conde, PhD
K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells
Mol Cell. 2013 Aug 8;51(3):283-96.
Linares JF, Duran A, Yajima T, Pasparakis M, Moscat J, Diaz-Meco MT.
PMID: 23911927; PMCID: PMC3971544
Read MoreMaria Diaz-Meco Conde, PhD
c-Myc phosphorylation by PKCζ represses prostate tumorigenesis
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6418-23.
Kim JY, Valencia T, Abu-Baker S, Linares J, Lee SJ, Yajima T, Chen J, Eroshkin A, Castilla EA, Brill LM, Medvedovic M, Leitges M, Moscat J, Diaz-Meco MT.
PMID: 23550155; PMCID: PMC3631641
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis
Cell. 2013 Jan 31;152(3):599-611.
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.
PMID: 23374352; PMCID: PMC3963830
Read MoreMaria Diaz-Meco Conde, PhD
p62: a versatile multitasker takes on cancer
Trends Biochem Sci. 2012 Jun;37(6):230-6.
Moscat J, Diaz-Meco MT.
PMID: 22424619; PMCID: PMC3531712
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
Feedback on fat: p62-mTORC1-autophagy connections
Cell. 2011 Nov 11;147(4):724-7.
Moscat J, Diaz-Meco MT.
PMID: 22078874; PMCID: PMC3290994
Read MoreMaria Diaz-Meco Conde, PhD
p62 is a key regulator of nutrient sensing in the mTORC1 pathway
Mol Cell. 2011 Oct 7;44(1):134-46
Duran A, Amanchy R, Linares JF, Joshi J, Abu-Baker S, Porollo A, Hansen M, Moscat J, Diaz-Meco MT.
PMID: 21981924; PMCID: PMC3190169
Read MoreMaria Diaz-Meco Conde, PhD
Simultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-kappaB activation and invasive prostate carcinoma
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12962-7.
Fernandez-Marcos PJ, Abu-Baker S, Joshi J, Galvez A, Castilla EA, Cañamero M, Collado M, Saez C, Moreno-Bueno G, Palacios J, Leitges M, Serrano M, Moscat J, Diaz-Meco MT.
PMID: 19470463; PMCID: PMC2722271
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
p62 at the crossroads of autophagy, apoptosis, and cancer
Cell. 2009 Jun 12;137(6):1001-4.
Moscat J, Diaz-Meco MT.
PMID: 19524504; PMCID: PMC3971861
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis
Cancer Cell. 2008 Apr;13(4):343-54.
Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, Moscat J.
PMID: 18394557
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
Cell signaling and function organized by PB1 domain interactions.
Mol Cell. 2006 Sep 1;23(5):631-40.
Moscat J, Diaz-Meco MT, Albert A, Campuzano S.
PMID: 16949360
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62
Cell Metab. 2006 Mar;3(3):211-22.
Rodriguez A, Durán A, Selloum M, Champy MF, Diez-Guerra FJ, Flores JM, Serrano M, Auwerx J, Diaz-Meco MT, Moscat J.
PMID: 16517408
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis
Dev Cell. 2004 Feb;6(2):303-9.
Durán A, Serrano M, Leitges M, Flores JM, Picard S, Brown JP, Moscat J, Diaz-Meco MT.
PMID: 14960283
Read MoreMaria Diaz-Meco Conde, PhD
Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62
Mol Cell Biol. 1998 May;18(5):3069-80.
Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT.
PMID: 9566925; PMCID: PMC110686
Read MoreMaria Diaz-Meco Conde, PhD, Jorge Moscat, PhD
The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C
Cell. 1996 Sep 6;86(5):777-86.
Díaz-Meco MT, Municio MM, Frutos S, Sanchez P, Lozano J, Sanz L, Moscat J.
PMID: 8797824
Read More