Todd A. Fehniger, MD, PhD

Todd A. Fehniger, MD, PhD

Professor

Address:
Division of Oncology
Mail Stop 8007-0057-06
Washington University
660 South Euclid Avenue
St. Louis, MO 63110

Room 638 Southwest Tower (office)

Room 634 Southwest Tower (lab)
Ph: 314-747-1547 (lab)

Admin:
Gina Gentilini
ggentilini@wustl.edu

Clinical Interests
  • Lymphoma
  • Leukemia
  • Immunotherapy
  • Hematopoietic cell transplantation
Research Interests
  • Innate immunity
  • Natural killer cell biology
  • Micro RNAs
  • Cytokines
  • Natural killer cell based therapeutics
Research

My basic science research program focuses on benign and malignant lymphocyte biology, which informs a translational immunotherapy effort to develop novel treatments for cancer patients.

Basic and Translational Natural killer (NK) Cell Biology: The long term goals of this research program are to better understand the cellular networks and molecular programs that regulate natural killer (NK) cell development and activation, and translate basic NK cell biology into novel treatments for patients with cancer.

  • The role of microRNAs in regulating NK cell development and function
    MicroRNAs are a large family of non-coding RNAs that control the production of proteins. Our laboratory uses next-generation sequencing to identify the expressed microRNAs in human and mouse NK cells, including developmental and functional subsets, and NK cells arising in different tissue. We use mouse genetic models to investigate the mechanistic role of microRNAs in NK cell development and function. In addition, we have developed techniques to elucidate the regulatory role of microRNAs in human NK cells. Global knockout of microRNA biogenesis (dicer1) in mouse NK cells has revealed a marked impact on NK cell development and functionality. The study of how individual microRNAs expressed in NK cell impact NK cell biology is ongoing, and recent work has identified a role for miR-155 in setting the activation threshold of NK cells.
mir-155 regulates the NK cell activation threshold by targeting multiple activating signnaling pathway members. Schema showing signaling intermediates downstream of ITAM coupled receptors in NK cells, with miR-155 targeting directly detected biochemically using RISC-seq, comparing miR-155 and wild type NK cells. Inhibitors to calcineurin and the PI3K pathway rescued the IFN-y production advantage by miR-155 NK cells, implicating those pathways in the MiR-155 'tuned' activation threshold. Adapted from Figure 8 of Sullivan RP et al, J Immunol 191:5904, 2013.
  • Utilizing cytokines to function enable NK cells
    Cytokines are the communication system used by immune cells to signal the need to home to sites of infection or cancer, grow, survive, and become highly functional. Our laboratory studies how cytokines may activate human and mouse NK cells, with the translational goal of developing new immunotherapy approaches. One example is cytokine-induced memory-like NK cells, where our laboratory in collaboration with Dr. Megan Cooper, identified a novel way to enhance human NK cell activity against cancer cell targets. This involves a brief, combined pre-activation with IL-12, IL-15, and IL-18. Ongoing work evaluates the mechanisms whereby human CIML NK cells maintain enhanced functionality and establishes the framework for their use as cancer immunotherapy.
  • Clinical trials utilizing NK cells or drugs that enhance NK cell function 
    Lenalidomide in hematologic malignancies. Two phase 2 trials of the immunomodulatory drug lenalidomide have shown activity in acute myeloid leukemia and Hodgkin lymphoma, and our laboratory is investigating the impact of lenalidomide on NK cells in patients. A third clinical trial investigates the potential for using lenalidomide after a stem cell transplant for patient with relapsed Hodgkin lymphoma. These clinical studies have been performed in collaboration with Drs. Nancy Bartlett and Ravi Vij.

    CIML NK cells for relapsed or refractory AML. This is a first in human phase 1 study of allogeneic CIML NK cells (pre-activated with IL-12, IL-15, and IL-18), an approach identified in our laboratory in human NK cell pre-clinical studies. The goal of this trial is to establish the safety of this adoptive immunotherapy and improve our understanding of human CIML NK cell biology in vivo. This study is being performed in collaboration with Dr. Rizwan Romee, who oversees the clinical trial.

Additional clinical trials involving NK cells include: selecting a favorable KIR donor in unrelated HSCT for AML with the goal of this study is to utilize killer cell immunoglobulin-like receptor (KIR) genes to choose the optimal unrelated donor for patients undergoing stem cell transplantation for AML; and using CNDO-109 activated allogeneic NK cells in a phase 1 / 2 clinical trial in which NK cells are administered to acute myeloid leukemia patients who have obtained a complete remission, but require additional treatment to prevent relapse.

Lymphoma Genomics and Biology
The long term goals of this research program are to advance our understanding of how lymphoma develops and progresses, and use this knowledge to develop new prognostic and therapeutic approaches for lymphoma patients.

  • Clinical and pathogenic impact of genomic variants in follicular NHL
    Discovery and targeted next-generation DNA sequencing of follicular lymphoma will be used to define the recurrence of somatic genomic alterations and their impact on clinical outcomes. This project is performed in collaboration with The Genome Institute at Washington University.
Fehniger Lab
Profiles (publications)
WU Physician Bio

Biosketch

Education

  • 2002: MD, The Ohio State University, College of Medicine and Public Health, Columbus, OH
  • 2000: PhD in Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, College of Medicine and Public Health, Columbus, OH
  • 1994: BS in Biological Sciences with High Distinction, State University of New York (SUNY), Buffalo, NY

Post-Graduate Training

  • 2008-2004: Fellow, Hematology and Oncology, Washington University School of Medicine, St. Louis, MO
  • 2004-2002: Intern and Resident, Internal Medicine, Physician Scientist Training Pathway, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO

Academic Positions & Employment

  • present-2020: Professor, Department of Medicine, Washington University School of Medicine, St. Louis, MO
  • 2020-2015: Associate Professor, Department of Medicine, Washington University School of Medicine, St. Louis, MO
  • 2014-2008: Assistant Professor, Department of Medicine, Washington University School of Medicine, St. Louis, MO

University & Hospital Appointments & Committees

  • present-2018: Scientific Co-Director, Center for Gene and Cellular Immunotherapy, Division of Oncology, Department of Medicine, Washington University School of Medicine
  • present-2018: Director, Biological Therapy Core Facility, Siteman Cancer Center, Washington University School of Medicine
  • present-2017: K12 Training Grant Review Committee
  • present-2014: Member, WUSM Center for Human Immunology and Immunotherapy Programs (CHIIPs)
  • present-2008: Member, Siteman Cancer Center, Hematopoietic Development and Malignancy Program; Lymphoma Program Co-Leader
  • present-2008: Member, Division of Biology and Biomedical Sciences, Immunology Program, Washington University
  • present-2008: Member, Institute for Clinical and Translational Sciences (ICTS), Washington University
  • 2021, 2019-2014: Member, Siteman Cancer Center Investment Program Study Section
  • 2018-2017: KL2 Training Grant Review Committee
  • 2018-2014: Leukemia SPORE DRP Review Committee
  • 2017-2014: Reviewer, BJHF/ICTS Clinical and Translational Research Funding Program
  • 2013-2010: Siteman Cancer Center Shared Resource Review Committee
  • 2013-2009: Reviewer, Translational Oncology Group Seed Funding, Division of Oncology
  • 2011-2009: Data Safety Monitoring Committee for investigator initiated clinical trial 07-0916: “Phase I trial of intravenous Decitabine in combination with Arsenic trioxide and Ascorbic acid in patients with myelodysplastic syndromes”
  • 2009: Reviewer, BJHF/ICTS Clinical and Translational Research Funding Program

Board Certification

  • 2009, 2019: ABIM Certified, Medical Oncology
  • 2006: ABIM Certified, Internal Medicine

Honors & Awards

  • 2018: Siteman Cancer Center “Rock Doc” Award
  • 2018: Siteman Cancer Center Lymphoma Team Science Award
  • 2017: Children’s Discovery Institute, Interdisciplinary Award
  • 2017: V Scholar Translational Research Award, V Foundation for Cancer Research
  • 2016: Elected Member, American Society for Clinical Investigation (ASCI)
  • 2014: Gabrielle’s Angel Foundation Medical Award
  • 2014: AAI Junior Faculty Travel Award
  • 2013: ASH Bridge Grant Program Award (declined when R01 funded)
  • 2013: Follicular Lymphoma Pathway Award, Lymphoma Research Foundation
  • 2012: V Scholar Award, V Foundation for Cancer Research
  • 2009: ASH Scholar Award (Basic Science, Junior Faculty)
  • 2008: ASCO Merit Award
  • 2008: HHMI Physician Scientist Early Career Award
  • 2008: Edward Mallinckrodt, Jr. Foundation Award
  • 2007: American Society of Clinical Oncology (ASCO) Young Investigator Award
  • 2007: Future Leader in Hematology Award (Celgene)
  • 2001, 1999: American Society of Hematology (ASH) Travel Award
  • 2000: ASH Medical Student (Trainee) Award
  • 2000: American Association of Immunologists (AAI)-Huang Foundation Trainee Achievement Award
  • 1996: Howard Hughes Medical Institute (HHMI) Research Fellowship for Medical Students

Editorial Responsibilities

  • present-2015: Review Editor, Frontiers in Molecular Innate Immunity
  • 2023-2018: Deputy Editor, The Journal of Immunology
  • 2018-2016: Editorial Board, European Journal of Immunology
  • 2018-2015: Editorial Board, Blood
  • 2018: Editor, Wintrobe’s Clinical Hematology, Edition 14 (Greer, Arber, Rodgers, Means, Appelbaum, Dispenzieri, Glader, List, Fehniger, editors). Wolters Kluwer, 2018
  • 2015: Review Editor, Frontier in Immunology, NK cell biology

Peer-Review Service (Selected)

  • 2021: National Cancer Institute, P01 Study Section, Ad Hoc Member
  • 2021: Leukemia and Lymphoma Society, Career Development Program, Study Section
  • 2020: Leukemia and Lymphoma Society, SCOR External Site Reviewer for Baylor
  • 2019: NIH/NCI R01/R21 Immunotherapy and U54 Pediatric Immunotherapy Study Sections
  • 2017: Leukemia and Lymphoma Society, Career Development Program Study Section Member
  • 2017: NIH/NIAID P01 Special Emphasis Panel (ZAI1-AMC-A-M1) Study Section Member
  • 2016: NIH/NIAID UM1 Martin Delany Collaboratory to Cure HIV, Study Section Member
  • 2013: NIH/NIAID Human Immunology Project Consortium Grant Reviewer
  • 2013: Leukemia and Lymphoma Society, Quest for the Cures Study Section Member

Professional Societies & Organizations

  • present-2014: Site Co-PI, Clinical Immunotherapy Trials Network (CITN)
  • present-2010: American Association for Cancer Research
    • 2013: AACR Annual Meeting Education Committee, Member
  • present-2010: American Association of Immunologists
  • present-2008: Alliance Cooperative Group
    • Lymphoma Committee, Member
    • Lymphoma Translational Sciences, Vice Chair
  • present-2008: Society for Natural Immunity
    • 2024-2021: President
    • 2021-2018: President-Elect
  • present-2004: American Society for Transplantation and Cellular Therapy
  • present-2004: American Society of Hematology
    • 2023-2018: ASH Scientific Committee on Immunology and Host Defense