Human Oncology & Pathogenesis Program

The James Fagin Lab

Research

Pictured: James Fagin
James A. Fagin, MD
Head, Division of Subspecialty Medicine; Member, Human Oncology & Pathogenesis Program

Professor

The focus of the Fagin lab is to understand the pathogenesis and the biology of thyroid cancers at single cell resolution with the goal of identifying new mechanism-based therapies.  His group has been instrumental in characterizing somatic genetic changes associated with tumor initiation and progression in radiation-induced and sporadic thyroid cancer, and in defining their functional consequences. He showed that selective MEK and RAF kinase inhibitors restored thyroid differentiation and responsiveness to radioactive iodine in GEM models of the disease, which led to the development of innovative clinical trials showing significant promise of this therapeutic strategy. His group also defined novel mechanisms of adaptive resistance of BRAF-mutant thyroid cancers to MAPK pathway inhibitors. The improved efficacy of one of these approaches, the co-targeting of RAF and HER2/HER3 has recently been confirmed in phase II trials. In addition to these studies, the lab is currently working in the following areas:

  1. Investigation of the role of the HIPPO pathway as a rheostat regulating adaptive resistance to small molecules targeting the MAPK pathway in thyroid cancer and other cell lineages.

 

  1. Advanced thyroid cancers have increased frequency of mutations of genes encoding chromatin remodeling proteins, including several members of the SWI/SNF chromatin remodelling complex. His group is systematically exploring the impact of individual Swi/Snf and histone methyl transferase disruptions on the chromatin and transcriptional landscape of thyroid cancers in GEMM. Current evidence indicates that they lock thyroid tumor cells into an undifferentiated state that can no longer be reversed by MAPK pathway blockade, while creating new and unanticipated therapeutic vulnerabilities.

 

  1. A hallmark of anaplastic thyroid cancers is their heavy infiltration with T cells and myeloid cells. He is investigating how profound MAPK pathway inhibition reprograms these tumors at single cell resolution. The lab is also investigating how cell autonomous antigen presentation and the tumor microenvironment contribute to promote T cell cytotoxicity. In a related project, his group is collaborating with the Levine lab to investigate whether tumor-infiltrating myeloid cells harboring mutations of Tet2, Dnmt3a or Axsl1, which are hallmarks of clonal hematopoiesis, confer refractoriness to therapy in GEMM with Braf-driven ATC.

 

  1. The Fagin and Nai-Kong Cheung labs are collaborating to develop bispecific antibodies to target unique changes in the membrane proteome of thyroid cancers in response to MAPK pathway blockade.

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Fagin Lab

Publications

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People

Pictured: James Fagin

James A. Fagin, MD

Head, Division of Subspecialty Medicine; Member, Human Oncology & Pathogenesis Program

Professor

  • Physician-scientist James Fagin focuses on the pathogenesis of thyroid cancer and the role of oncogenic kinases.
  • MD, University of Buenos Aires School of Medicine (Argentina)
646-888-2136
Office Phone
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Members

Adrián Acuña Ruíz
Adrián Acuña Ruíz

Research Fellow

Katherine Berman
Katherine Berman

Senior Research Technician

Laura Boucai

Associate Attending

Alan L. Ho
Alan L. Ho

Associate Attending

Gnana Prakasam Krishnamoorthy
Gnana Prakasam Krishnamoorthy

Senior Research Scientist

Rona Lester
Rona Lester

Research Assistant

Aradya Nigam

Research Fellow

Tianyue Qin
Tianyue Qin

Research Technician

Mahesh Saqcena
Mahesh Saqcena

Senior Research Scientist

Vera Tiedje
Vera Tiedje

Senior Research Scientist

Brian Untch, MD
Brian Untch

Assistant Attending

Dina Vukel
Dina Vukel

Research Technician

Lab Alumni
Prasanna Tamarapu Parthasarathy

Research Assistant

Sasha Clark

Research Technician

Jennifer Cracchiolo

Fellow

Jose M. Dominguez Ruiz-Tangle

Visiting Investigator

Vanessa  Dos Anjos
Vanessa Dos Anjos

Senior Research Technician

Anthony Glover
Anthony Glover

Research Scholar

Jeffrey Knauf, PhD
Jeffrey Knauf

Associate Attending Biologist

Inigo Landa-Lopez
Inigo Landa-Lopez

Research Fellow

Luis Javier Leandro Garcia
Luis Javier Leandro Garcia

Research Fellow

Janet Li
Janet Li

Research Fellow

Kathleen Luckett
Kathleen Luckett

Research Technician

James Nagarajah
James Nagarajah

Research Associate

Gisele Oler, PhD
Gisele Oler

Research Fellow

Julio Ricarte Filho, PhD
Julio Ricarte Filho

Research Fellow

Maria Elena Rodriguez-Garcia-Rendueles
Maria Elena Rodriguez-Garcia-Rendueles

Research Scholar

Francesca Voza
Francesca Voza

Research Assistant

Lab Affiliations

Achievements

  • President, American Thyroid Association (2012)
  • UK Clinical Endocrinology Trust Medal Lecture Award (2011)
  • Sydney Ingbar Award, American Thyroid Association (2008)
  • Merck Prize, European Thyroid Association Award (2007)
  • Association of American Physicians Award (2001)
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  • American Society of Clinical Investigation Award (1998)

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Disclosures

Doctors and faculty members often work with pharmaceutical, device, biotechnology, and life sciences companies, and other organizations outside of MSK, to find safe and effective cancer treatments, to improve patient care, and to educate the health care community.

MSK requires doctors and faculty members to report (“disclose”) the relationships and financial interests they have with external entities. As a commitment to transparency with our community, we make that information available to the public.

James A. Fagin discloses the following relationships and financial interests:

  • Endocrine Society
    Provision of Services
  • International Thyroid Oncology Group
    Provision of Services (uncompensated)
  • Journal of the Endocrine Society
    Provision of Services
  • Kura Oncology
    Intellectual Property Rights
  • Loxo Oncology
    Provision of Services

The information published here is for a specific annual disclosure period. There may be differences between information on this and other public sites as a result of different reporting periods and/or the various ways relationships and financial interests are categorized by organizations that publish such data.


This page and data include information for a specific MSK annual disclosure period (January 1, 2020 through disclosure submission in spring 2021). This data reflects interests that may or may not still exist. This data is updated annually.

Learn more about MSK’s COI policies here. For questions regarding MSK’s COI-related policies and procedures, email MSK’s Compliance Office at [email protected].


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