Laboratory of Lymphomagenesis and Humanized Mouse Models

Principal Investigator: 
Giorgio Inghirami, M.D.

Our goal is to understand the mechanisms that drive the lymphoid transformation and the maintenance of the neoplastic phenotype, mainly in the T-cells lymphomas. Peripheral T cell lymphoma (PTCL) represents ~15% of all human lymphomas and comprises 30 different entities. PTCL heterogeneity underlies complex genomic fingerprints and a broad array of known and unknown driving events/mechanisms. We originally discovered the tumorigenic role of Anaplastic Lymphoma Kinase chimeras in Anaplastic Large cell Lymphomas (ALCL), and then proven the pathogenetic role of STAT3 in these neoplasms. We are currently studying how STAT3 regulates the transcription of coding and non-coding genes and modules tumor cells' epigenome. We are also dissecting its contribution to host-lymphoma interactions, using genomic and pharmacological approaches (STAT3 degraders, etc.). In the case of PTCL, only a handful of cell lines are available. Thus, we have generated a battery of Patient-Derived Tumor Xenografts (PDTX) representative of the most frequent entities of PTCL, B-cell lymphomas and acute leukemias. These models serve as a powerful tool to dissect the molecular mechanisms driving the neoplastic phenotype, and to investigate host responses in fully humanized animals (HuMice). HuMice are innovative platforms for establishing new therapeutic interventions and improving cell-mediated therapies (CAR-T and CAR-NK). 

Inghirami Lab Figure

Active Projects

  • Dissecting the STAT3 oncogenic addiction B and T cell lymphomas.
  • Modulating the expression of transcription factors using selective degraders to improve therapy and overcome resistant phenotypes.
  • Defining the genomic fingerprints of lymphomas as biomarkers for predicting drug responses.
  • Implementing new strategies targeting the host-lymphoma interactions to achieve tumor eradication.
  • Expand the PDTX library and test novel compounds in vitro using 2D and 3D systems and in vivo models.
  • Establishing novel mouse models using human normal and neoplastic elements.

Grants

Core Lead: Giorgio Inghirami, MD 
Among our goals, we intend to: 1) provide investigators with PDX tumors with relevant genomic and RNA-Seq characterization data, as well as any technical information and advice; 2) conduct preclinical studies with PDX tumor models, both tumor specific and/or covering multiple tumor type; 3) identify predictive biomarkers to better select appropriate treatments for specific cancer patient populations; 4) Define the genomic landscape of naive and treated PDX to identify genomic aberration linked/predictive of clinical responses.
MCL-RI Grant 180078-01 LLS

Core Lead: Giorgio Inghirami, MD 

To procure patient specimens, characterize and assess the specimens as required by projects and for clinical trials, provide data to the projects and other cores, bank tissue, and distribute tissue to the projects.

Core Lead: Giorgio Inghirami, MD 
The pre-clinical models and therapeutics core (PMTC) will assemble and characterize the reagents critical for this proposal including the wide array of clinically and molecularly annotated primary pathological samples, patient derived tumor xenograft (PDTX) models as well as patient derived organoids (PDO).
P01CA229100

Core Lead: Giorgio Inghirami, MD 
The ultimate goal of this P01 is to compare and contrast the impact of mutations in CTCF and cohesin regulatory proteins with the effect of mutant or deregulated oncogenic transcription factors (such as NOTCH1), histone-modifying enzymes (Polycomb and CREBBP/EP300), as well as enzymes that control DNA methylation (DNMT3A).
P01 CA229086

PI: Giorgio Inghirami, MD 
To define the therapeutic efficacy of CD137L-CAR-T in colon cancer preclinical models.
CTSC 2020-2021  

Co-PI: Giorgio Inghirami, MD 
The goal of this infrastructure grant is to establish and maintain a cohort of over 12,000 non-Hodgkin lymphoma (NHL) patients to support broad and cutting-edge research that identifies clinical (including co-morbid diseases), epidemiologic (including lifestyle and other exposures), host genetic, tumor, and treatment factors, as well as the interaction among these factors, on short and long-term outcomes.
U01 CA195568-01

Core Lead: Giorgio Inghirami, MD 
The Preclinical Models and Therapeutics Core will continue to facilitate xenografting, cell line development and organoid generation from primary specimens of peripheral T-cell lymphoma (PTCL).  The central aim of the core is to provide the Projects and larger PTCL research community with tractable models for discovery biology and therapeutic validation.  This includes models of acquired resistance, both from patients after therapeutic failure and upon drug exposure within preclinical models.
7026-21 LLS SCOR 

Co-PI: Giorgio Inghirami, MD 
To define the role of the host in lymphoma progression and response to therapy.
R01 CA242069-01A1

Lab Team

Inghirami Lab members

Additional Key Academic Personnel

Giuseppina Astone
Post Doc
gia4001@med.cornell.edu
Francesco Ciccarese Ciccarese
Visiting Fellow
frc4005@med.cornell.edu

Contact Information

Giorgio Inghirami, MD
Professor of Pathology and Laboratory Medicine
Vice Chair for Hematopathology
Weill Cornell Medicine

1300 York Ave
New York, NY 10065
Phone: 
212-746-5616

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700