For information about COVID-19, including symptoms and prevention, please read our COVID-19 patient guide. Please also consider supporting Weill Cornell Medicine’s efforts against the pandemic.

Metabolic Alterations in Prostate Tumorigenesis

Massimo Loda, MD, Principal Investigator

The Loda laboratory has been focused on understanding the mechanisms responsible for metabolic rewiring in prostate tumorigenesis, with a specific interest in lipid metabolism and its regulation. The ultimate goal is to identify metabolic vulnerabilities that can be targeted therapeutically. Our approach is multidisciplinary, utilizing cell lines, orthotopic tumor xenograft, genetically engineered murine models and human tumors.

We have developed, pioneered and disseminated several techniques in molecular pathology, including multiplexed immunohistochemistry and in situ hybridization, ex vivo human tumor organotypic culture method to investigate antitumoral pharmacological properties that preserves the original cancer microenvironment. The landscape and related functional significance of genomic alterations in prostate cancer is studied in large, international cohorts such as the Prostate TCGA Consortium and the Pan Prostate Cancer Group that Dr. Loda co-leads.
The stroma is recognized as an important contributor in the process of carcinogenesis, and a driver of cancer progression. Experimental models demonstrate that altered stromal cells can induce tumor formation in non-cancerous prostate epithelial cells. It is also clear that the stroma morphologically and functionally changes in the presence of cancer. Despite the overwhelming evidence for the importance of the microenvironment in tumor progression, there is limited knowledge on its cellular composition and on how stromal cells signal to epithelial tumor cells, modifying their functional behavior. The Loda lab aims to construct a precise molecular and morphologic stromal map using laser capture microdissection, single cell RNASeq and multiplex immunofluorescence, in order to gain mechanistic insights as to the interaction between tumor cells and the stromal microenvironment that surrounds it.


Active Projects:

  • Pharmacologic inhibition of lipogenesis as therapeutic option for castration resistant prostate cancer
  • Lipid Elongation via ELOVL5: A Novel Target for Advanced Prostate Cancer
  • Functional atlas of mouse and human prostate cancer mesenchyme
  • The role of TMPRSS2_ERG fusions in modulating tumor microenvironment in prostate cancer
  • Metabolism rewiring by FASN inhibition alters cancer microenvironment
  • The relative contribution of endogenous vs. exogenous lipids in prostate cancer
  • Integrative genomics, transcriptomics, metabolomics, and histopathology studies in large prostate cancer cohorts
  • Metabolomics of prostate cancer Gleason score in tumor tissue and serum
  • Highly multiplexed spatial transcriptomics and proteomics

Active Grants:

  • Pharmacologic Inhibition of Lipogenesis Suppresses AR and its Splice Variants to Inhibit Progression of Castration Resistant Prostate Cancer (W81XWH-17-1-0483)
    PI: Massimo Loda, MD
    Role: Initiating PI
    DOD PCRP Impact Award 9/30/17-9/29/22

    The specific aims of this project are 1) Determine the role of FASN inhibition on enzalutamide and abiraterone resistance, where resistance is due to AR-Vs expression; 2) Generation of organoids from human PDX models evaluated and characterized in aim 1 and from primary and metastatic human prostate cancer; 3): Mechanism of AR regulation by FASN inhibition.

  • Precision Interception of Aggressive Prostate Cancer in African American Men (P20CA233255)
    PI: Massimo Loda, MD
    Role: Core Director, Biospecimen and Biomarker Core (BBC)
    National Institutes of Health/National Cancer Institute 12/1/18-11/30/21

    Our grant proposes a “precision interception” approach designed to impede cancer progression at early stages and avoid development of lethal disease in AA PCa cases. We will focus on newly diagnosed or recurrent AA PCa patients, with the goal to develop and implement tools that can “intercept” the development of castrate-resistant or metastatic PCa and death from PCa in AA men. These approaches can thereby reduce PCa-specific disparities in mortality experienced by AA men. This P20 grant is composed of three multidisciplinary research projects and two cores, as well as a developmental research program.

  • Lipid Elongation via ELOVL5: A Novel Target for Advanced Prostate Cancer (W81XWH-19-1-0566)
    PI: Massimo Loda, MD
    DOD PCRP Idea Development Award 9/30/19 – 9/29/22

    Our proposal seeks to demonstate that ELOVL5 activity is critical to PCa progression by retuning the properties of cellular membranes, and is an exploitable new target for Castration Resistant Prostate Cancer (CRPC).

Completed Research Support (selected from various over the past three years)

  • DF/HCC SPORE in Prostate Cancer (P50CA90381)
    PI: Massimo Loda, MD
    National Institutes of Health/National Cancer Institute 7/1/13-6/30/19

    This SPORE is focused on several important themes in prostate cancer: 1) the identification of lethal prostate cancer using genetic and genomic approaches and 2) understanding the role of metabolism on the development of lethal prostate cancer, and understanding the mechanism of primary and secondary resistance to hormonal therapy and finally elucidating new targets for therapy in men with advanced disease. 

  • Molecular Link between Metabolic Syndrome and Prostate Cancer (R01CA131945)
    PI: Massimo Loda, MD
    National Institutes of Health/National Cancer Institute 12/1/07-7/31/19

    We hypothesize that PCa arising in patients with MetS is characterized by a unique molecular phenotype driven by the inactivation of AMPK in prostate tumors cells.

  • Targeting the p110beta isoform of P13 kinase in prostate cancer (R01CA187918)
    PI: Massimo Loda, MD
    National Institutes of Health/National Cancer Institute 4/1/15-3/31/20

    In this grant, we propose to evaluate the therapeutic potential of a novel class of inhibitors in prostate cancer in vitro and in vivo using human cancer cell lines, genetic mouse models as well as primary human prostate tumor explants, to develop biomarkers predictive of response to p110ß inhibition, and to identify optimal combination partner agents for p110ß-based therapy. The studies proposed in this grant will likely provide important information that will help to optimize the clinical impact of this class of inhibitors in PTEN-deficient tumors.

Selected Publications

Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell-Level PI3K Pathway Activation

Massimo Loda, MD

Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell-Level PI3K Pathway Activation

Clin Cancer Res. 2020 Sep 10. 

Stopsack KH, Huang Y, Tyekucheva S, Gerke TA, Bango C, Elfandy H, Bowden M, Penney KL, Roberts TM, Parmigiani G, Kantoff PW, Mucci LA, Loda M.

PMID: 32913135.

Read More

Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention

Massimo Loda, MD

Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention

Adv Drug Deliv Rev. 2020 Jul 23:S0169-409X(20)30097-1. 

Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV.

PMID: 32711004

Read More

High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

Massimo Loda, MD

High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

Nat Commun. 2019 Sep 25;10(1):4358. 

Labbé DP, Zadra G, Yang M, Reyes JM, Lin CY, Cacciatore S, Ebot EM, Creech AL, Giunchi F, Fiorentino M, Elfandy H, Syamala S, Karoly ED, Alshalalfa M, Erho N, Ross A, Schaeffer EM, Gibb EA, Takhar M, Den RB, Lehrer J, Karnes RJ, Freedland SJ, Davicioni E, Spratt DE, Ellis L, Jaffe JD, DʼAmico AV, Kantoff PW, Bradner JE, Mucci LA, Chavarro JE, Loda M, Brown M.

PMID: 31554818; PMCID: PMC6761092.

Read More

Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer

Massimo Loda, MD

Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer

Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):631-640. 

Zadra G, Ribeiro CF, Chetta P, Ho Y, Cacciatore S, Gao X, Syamala S, Bango C, Photopoulos C, Huang Y, Tyekucheva S, Bastos DC, Tchaicha J, Lawney B, Uo T, D'Anello L, Csibi A, Kalekar R, Larimer B, Ellis L, Butler LM, Morrissey C, McGovern K, Palombella VJ, Kutok JL, Mahmood U, Bosari S, Adams J, Peluso S, Dehm SM, Plymate SR, Loda M.

PMID: 30578319; PMCID: PMC6329966.

Erratum in: Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18893. 

Read More

Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer

Massimo Loda, MD

Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer

Nat Commun. 2017 Sep 4;8(1):420. 

Tyekucheva S, Bowden M, Bango C, Giunchi F, Huang Y, Zhou C, Bondi A, Lis R, Van Hemelrijck M, Andrén O, Andersson SO, Watson RW, Pennington S, Finn SP, Martin NE, Stampfer MJ, Parmigiani G, Penney KL, Fiorentino M, Mucci LA, Loda M.

PMID: 28871082; PMCID: PMC5583238.

Read More

Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues

Massimo Loda, MD

Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues

Mol Cancer Res. 2017 Apr;15(4):439-447.

Cacciatore S, Zadra G, Bango C, Penney KL, Tyekucheva S, Yanes O, Loda M.

PMID: 28074002; PMCID: PMC5552883.

Read More

The Molecular Taxonomy of Primary Prostate Cancer

Massimo Loda, MD

The Molecular Taxonomy of Primary Prostate Cancer

Cell. 2015 Nov 5;163(4):1011-25.

Cancer Genome Atlas Research Network (incl. Massimo Loda)

PMID: 26544944; PMCID: PMC4695400.

Read More

AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Massimo Loda, MD

AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Cancer Res. 2014 Dec 15;74(24):7198-204.

Priolo C, Pyne S, Rose J, Regan ER, Zadra G, Photopoulos C, Cacciatore S, Schultz D, Scaglia N, McDunn J, De Marzo AM, Loda M.

PMID: 25322691; PMCID: PMC4267915.

Read More

De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Massimo Loda, MD

De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Cell Cycle. 2014;13(5):859-68.

Scaglia N, Tyekucheva S, Zadra G, Photopoulos C, Loda M.

PMID: 24418822; PMCID: PMC3979921.

Read More

A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis

Massimo Loda, MD

A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis

EMBO Mol Med. 2014 Apr;6(4):519-38.

Zadra G, Photopoulos C, Tyekucheva S, Heidari P, Weng QP, Fedele G, Liu H, Scaglia N, Priolo C, Sicinska E, Mahmood U, Signoretti S, Birnberg N, Loda M.

PMID: 24497570; PMCID: PMC3992078

Erratum in: EMBO Mol Med. 2014 Oct;6(10):1357

Read More

The ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR degradation

Massimo Loda, MD

The ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR degradation

Oncogene. 2013 Mar 28;32(13):1660-9. 

Liu Z, Zanata SM, Kim J, Peterson MA, Di Vizio D, Chirieac LR, Pyne S, Agostini M, Freeman MR, Loda M.

PMID: 22710717; PMCID: PMC3866888.

Read More

MYC is activated by USP2a-mediated modulation of microRNAs in prostate cancer

Massimo Loda, MD

MYC is activated by USP2a-mediated modulation of microRNAs in prostate cancer

Cancer Discov. 2012 Mar;2(3):236-47.

Benassi B, Flavin R, Marchionni L, Zanata S, Pan Y, Chowdhury D, Marani M, Strano S, Muti P, Blandino G, Loda M.

PMID: 22585994; PMCID: PMC3523361.

Read More

Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors

Massimo Loda, MD

Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors

Proc Natl Acad Sci U S A. 2010 May 4;107(18):8352-6. 

Vaira V, Fedele G, Pyne S, Fasoli E, Zadra G, Bailey D, Snyder E, Faversani A, Coggi G, Flavin R, Bosari S, Loda M.

PMID: 20404174; PMCID: PMC2889536.

Read More

A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression

Massimo Loda, MD

A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression

Cancer Cell. 2008 Aug 12;14(2):146-55. 

Majumder PK, Grisanzio C, O'Connell F, Barry M, Brito JM, Xu Q, Guney I, Berger R, Herman P, Bikoff R, Fedele G, Baek WK, Wang S, Ellwood-Yen K, Wu H, Sawyers CL, Signoretti S, Hahn WC, Loda M, Sellers WR. 

PMID: 18691549; PMCID: PMC2583442

Read More

The isopeptidase USP2a protects human prostate cancer from apoptosis

Massimo Loda, MD

The isopeptidase USP2a protects human prostate cancer from apoptosis

Cancer Res. 2006 Sep 1;66(17):8625-32. 

Priolo C, Tang D, Brahamandan M, Benassi B, Sicinska E, Ogino S, Farsetti A, Porrello A, Finn S, Zimmermann J, Febbo P, Loda M.

PMID: 16951176.

Read More

The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer

Massimo Loda, MD

The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer

Cancer Cell. 2004 Mar;5(3):253-61. 

Graner E, Tang D, Rossi S, Baron A, Migita T, Weinstein LJ, Lechpammer M, Huesken D, Zimmermann J, Signoretti S, Loda M.

PMID: 15050917

Read More

Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27

Massimo Loda, MD

Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27

Mol Endocrinol. 2001 May;15(5):765-82.

Waltregny D, Leav I, Signoretti S, Soung P, Lin D, Merk F, Adams JY, Bhattacharya N, Cirenei N, Loda M.

PMID: 11328857

Read More

Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas

Massimo Loda, MD

Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas

Nat Med. 1997 Feb;3(2):231-4. 

Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M.

PMID: 9018245.

Read More

Weill Cornell Medicine Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464 Fax: (212) 746-8192