SPORE in Leukemia


Principal Investigator: Daniel Link, MD

The Specialized Programs of Research Excellence (SPORE) are the cornerstone of the National Cancer Institute’s effort to promote collaborative, interdisciplinary translational cancer research. Each SPORE is focused on a specific organ site and is designed to enable the rapid and efficient movement of basic scientific findings into clinical settings as well as to determine the biological basis for observations made in individuals with cancer.

The Washington University SPORE in Leukemia is one of only three SPOREs in the United States focused on leukemias and myelodysplastic syndromes (MDS). Washington University has been at the forefront of genomic studies in AML and MDS. This ongoing basic research has identified several novel recurring mutations in MDS/AML and is defining the importance of clonal heterogeneity in AML or MDS to clinical outcome. In this SPORE, we leverage our expertise in cancer genomics, immunology, and hematopoiesis to develop innovative translational research in leukemia. Our long-term goal is to develop novel biomarkers and treatments for leukemias and MDS and to develop and promote innovative translational leukemia research.

Our SPORE in Leukemia includes the following four translational projects:

Project 1:  Molecular determinants of decitabine responsiveness
  • Basic Science Co-Leader: Timothy Ley, MD
  • Clinical Science Co-Leader: John Welch, MD, PhD
Project 2:  Targeting the bone marrow microenvironment in acute lymphocytic
  • Basic Science Co-Leader: Daniel Link, MD
  • Clinical Science Co-Leader: Geoffrey Uy, MD
Project 3:  Development of RNA splicing modulators for myelodysplastic syndromes and AML
  • Basic Science Co-Leader: Timothy Graubert, MD
  • Clinical Science Co-Leader: Matthew Walter, MD
Project 4: Epigenetic modulation of graft versus host disease and graft versus leukemia
  • Basic Science Co-Leader: John F. DiPersio, MD, PhD
  • Clinical Science Co-Leader: Peter Westevelt, MD, PhD

These projects are supported by three shared resources:

  1. Biospecimen Processing
  2. Biostatistics
  3. Administration

This SPORE also supports a Career Development Program to recruit and mentor new investigators in translational leukemia research and a Developmental Research Program to support innovative translational concepts.

SPORE Shared Resources (Cores)

Core A: Biospecimen Processing

Director: Peter Westervelt, MD, PhD
Co-DirectorMark Watson, MD, PhD

The Biospecimen Processing Core (Core A) is responsible for the identification and enrollment of every patient referred to the Siteman Cancer Center with newly diagnosed and relapsed hematologic malignancy (excluding multiple myeloma). The pathologic material from these patients will be banked using the existing Siteman Cancer Center (SCC) Tissue Processing Core (TPC), and clinical data will be tracked prospectively in a clinical database.

Core B: Biostatistics

Director: J. Philip Miller

The Biostatistics Core provides resources to assist in the planning, conduct and analysis of the proposed research in such a way that quantitative analyses are appropriate and illuminating. The Core also assists in the dissemination of appropriate information both within and external to the SPORE and the Siteman Cancer Center (SCC). The Core is staffed by a dedicated biostatistician for each of the 4 projects. In addition a designated faculty member is devoted to collaborations concerning specialized bioinformatics issues. The Biostatistics Core will serve as a resource and collaborator for the four main projects proposed in this application, Career Development Program and Developmental Research Program projects and the SPORE Cores.

Core C: Administration

Director: Daniel Link, MD

The Administration Core provides executive oversight and administrative support for all of the projects and cores that comprise the Leukemia SPORE. The goal of the Administration Core is to monitor the activities of all of the program components, to comply with all local and federal guideline for grant administration, and to facilitate communication and collaboration among the program members.

Career Enhancement Program (CEP)

Matthew Walter, MD, and Geoffrey Uy, MD

The goal is to recruit and support new independent investigators in the field of translational leukemia research. The research initiatives that will be funded by the CDP are expected to have a major translational component, focusing on leukemia etiology, diagnosis, early detection, treatment, or population science.


Junior faculty (Instructor or Assistant Professor) without RO1 or equivalent grant or senior post-doctoral fellows (PhD, MD, or MD-PhD) who have a written commitment from their department chair indicating promotion to Instructor or Assistant Professor by the time of the award also will be eligible.


One to two awards of $60,000 (direct cost) will be made annually. The second year of funding is contingent upon adequate progress.

Submission Guidelines

The current application cycle is now open. Applications will be accepted until May 1, 2017 with funding to begin July 1, 2017. Applications must be submitted through proposalCENTRAL. For additional information, please contact Amy Abrams at

2015 Awardees

Cooper_MattMatthew Cooper, PhD

Project title: Combination therapy of immunomodulating agents for AML treatment in a novel human CD3ε mouse

Recent advances in immunotherapy have demonstrated the potential of harnessing the immune system to fight cancer.  Progress in this area has been hampered by a lack of an animal model to test new immunotherapy reagents, such as bispecific antibodies that direct immune cells to attach cancer cells.  To this end, we have generated a novel transgenic mouse model that may overcome this limitation.  Specifically, we are performing studies to see if this mouse model will allow us to test new bispecific antibodies for their ability to activate the immune system against leukemia. 

Duncavage_EricEric Duncavage, MD
Project Title:  Quantitative tumor burden monitoring in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by persistent low blood counts, cellular dysplasia, and an increased risk of transformation to leukemia with an average annual incidence of 45,000 cases.  While many patients with MDS are treated with prolonged courses of non-cytotoxic chemotherapy, up to one third of cases will eventually progress to acute leukemia and require treatment with cytotoxic chemotherapy or allogenic bone marrow transplant.  A major unmet clinical need is the ability to accurately monitor MDS patients for treatment response and progression to leukemia. In this study we propose to use newly developed ultra-sensitive sequencing methods and multi-parameter flow cytometry to monitor disease burden in MDS patients in enrolled in clinical trials.  The data generated in this study will allow us to establish the feasibility of using rapid, inexpensive sequencing methods for monitoring of therapeutic response in MDS patients including using less-invasive peripheral blood samples.

2014 Awardees

schuettpelz_lLaura Schuettpelz, PhD
Project title: Elucidating the role of enhanced toll like receptor signaling in myelodysplastic syndrome

There is increasing evidence that inflammation may contribute to cancer. In this proposal, we focus on toll like receptor signaling. Toll like receptors (TLRs) are genes that recognize pathogens, such as bacteria, and help shape the immune response. Augmented TLR signaling is associated with myelodysplastic syndromes (MDS), a group of blood stem cell disorders that are associated with abnormal blood cell formation and a high risk of progression to acute leukemia. The role of TLRs in the pathogenesis of MDS is not known, however, and in this study we will determine if enhanced TLR expression synergizes with common genetic mutations found in patients with MDS to promote progression of the disease. Ultimately, we hope that drugs targeting TLRs may be useful in the treatment of MDS.

spencerDavid Spencer, PhD
Project title: HOX gene regulation in hematopoiesis and AML

The long-term goal of this study is to understand how mutations in acute myeloid leukemia (AML) affect gene regulation and expression to cause cancer. In this project, we focus on HOX genes, which are involved in regulating “self-renewal” in normal stem cells. This capacity is important for normal stem cell function, but abnormal self-renewal contributes to leukemia development and allows cancer cells to continually divide in the bone marrow. Here, we focus on understanding how HOX genes are regulated in normal hematopoietic cells and in leukemia. We will use state-of-the-art genomic approaches to define the regulatory DNA elements that govern HOX gene expression in both normal and leukemic cells, and importantly, whether key differences exist between normal and malignant HOX gene regulation. These studies may lead to strategies for disrupting HOX self-renewal pathways in leukemia cells, which may yield broadly applicable therapeutic approaches for AML.

Developmental Research Program (DRP)

Lee Ratner, MD, PhD, and Daniel Link, MD

The goal is to support innovative translational leukemia research. Proposed projects will be reviewed with the intent that they will develop sufficiently, within one-two years, to be submitted for external peer-reviewed funding. For projects with a clinical trial, they must be ready to study activation within six months of award.


All faculty members (instructor level or higher) are eligible. In addition, senior post-doctoral fellows who have a written commitment from their department chair indicating promotion to Instructor or Assistant Professor by the time of the award will be eligible. Preference will be given to junior faculty or established investigators with a new translational leukemia research focus.


Up to three projects will be awarded a maximum of $70,000 (direct costs) on an annual basis. Selected projects may be considered for a second year of funding based on a competitive renewal.

Submission Guidelines

The current application cycle is now open.  Applications will be accepted until May 1, 2017 with funding to begin July 1, 2017.  Applications must be submitted through proposalCENTRAL.  For additional information, please contact Amy Abrams at

2015 Awardees

choi_kKyunghee Choi, PhD
Project title: TS-GATA-Ebox Gene Regulatory Network in HSC Derivation and Expansion

Embryonic stem (ES) or induced pluripotent stem (iPS) cells can, in theory, be used to generate unlimited amounts of virtually any tissue type.  There is tremendous interest in using these stem cells to regenerate heart, brain, blood, or other tissue in patients with cancer or degenerative diseases.  Our research will test a novel approach to enhance the differentiation of stem cells into blood cells.  Specifically, our data suggest that expression of three genes (ETV2, GATA2 and Scl) in ES cells should enhance the generation of functional hematopoietic (blood) stem cells.  This research, if successful, would provide a new source of blood stem cells to treat a wide variety of blood disorders, including leukemia. 

Lian_MMin Lian, MD, PhD, MPH
Project title: Multilevel determinants of survival among patients following HSCT

Leukemia, lymphoma and myeloma, are common hematopoietic malignancies in the United States. Hematopoietic stem cell transplant (HSCT) is a standard therapy procedure for patients diagnosed with primary hematopoietic malignancies. Despite well-known effectiveness of HSCT treatment, the survival of patients following HSCT still remains poor. We propose to conduct a multilevel analysis, using clinical data from patients who received HSCT due to these three hematopoietic malignancies, to identify risk factors (at multiple levels) associated with the survival of HSCT patients. We expect the study findings will help develop intervention strategy to improve the survival of patients following HSCT.

2014 Awardees

ley3Timothy Ley, MD
Project title: Role of Cold Shock Domain Proteins in Acute Myeloid Leukemia development

Our lab focuses on understanding the molecular changes that transform normal blood cells into leukemia cells. We recently have become interested in a protein called YBX1, which is expressed at a high level in blood stem cells and leukemia cells, but not mature blood cells. Cells that lack this protein are not able to sustain a high rate of proliferation and shut themselves down, using a process called cellular senescence. To study the function of Ybx1 in both normal and leukemic blood cells, we generated mice that express a truncated form of this protein. The blood stem cells in these mice are at a disadvantage when they are transplanted into recipient mice. When a leukemia-initiating oncogene is expressed in blood cells that contain the truncated Ybx1 protein, the leukemia cells also have a disadvantage. The purpose of this study is to determine exactly how the truncated form of Ybx1 interferes with proliferation of normal blood stem cells and leukemia cells. By understanding how leukemia cells depend on Ybx1 to proliferate, we hope to design new therapies for leukemia in the future.

welch_john2John Welch, PhD
Project title: Inhibiting MYC transcription in primary mouse leukemia cells

High expression of the gene c-MYC is associated with aggressive leukemias and is implicated in approximately 70,000 annual cancer deaths in the United States. Although c-MYC was discovered nearly three decades ago, we have no approved therapies directed at this oncogene. In this project, we propose to identify novel drugs that inhibit c-MYC.

We have developed a novel mouse model that allows us to monitor c-MYC activity. Expression of c-MYC in these mice induces leukemia and causes the cells to glow green. The goal of this project is to optimize the technical aspects of this model so that we could use these leukemia cells to empirically screen thousands of compounds to find small molecules that prevent the cells from glowing green (e.g. small molecules that inhibit c-MYC function and thus the green reporter). The advantage of this approach compared with others is that the cells used will be active leukemia cells taken directly from a mouse, rather than a cell line that has been grown on plastic for decades. Ultimately, we believe this research will help us identify new drugs that target c-MYC and treat a wide range of cancers.

rettigMichael Rettig, PhD
Project title: CD123XCD3 DART for AML

The immune system, and in particular T lymphocytes, can be used to treat cancer. A cell surface protein named CD123 is uniquely expressed on acute myeloid leukemia (AML) cells but not on normal primitive hematopoietic stem cells. Dual Affinity Re-Targeting (DART) technology is a novel, bispecific antibody platform designed to eradicate AML (or other tumor) cells through co-engagement of a leukemia-specific cell surface marker (eg. CD123) and the T cell receptor (CD3) complex on T cells as effector cells. In this proposal we will being to evaluate the safety and potential activity of MGD006, a CD123 x CD3 DART molecule, in patients with AML whose disease is not expected to benefit from additional cytotoxic chemotherapy.


Clinical Trials

The Siteman Cancer Center offers many types of clinical trials, also called clinical studies or research protocols. At any given time, Siteman has more than 350 therapeutic trials under way.

For more information about any of the clinical trials listed on this site, call 314-747-7222 or 800-600-3606 toll free or e-mail

SPORE In Touch Patient E-Newsletter


As part of its commitment to patient care, The Washington University SPORE in Leukemia team at Siteman Cancer Center publishes its e-newsletter, SPORE In Touch, for leukemia patients and their families. The goal of this newsletter is to provide valuable information as an extension of our mission to offer world-class care, research and resources within the clinical and medical research communities.

SPORE In Touch is a digital publication that is distributed via email three times a year, and focuses on issues related to leukemia, myelodysplastic syndromes or stem cell transplantation. It features patient stories, physician interviews, clinical trial information, events and other milestones.

To learn more about the publication, please email or call 314-747-2274.

To subscribe, please click here.

You are of course free to unsubscribe at any time. We will never sell your information to a third party or use your contact information for any communication outside of the newsletter.

Contact Us

Siteman Cancer Center SPORE in Leukemia

Nancy Reidelberger
SPORE Administrator
Phone: 314-362-9337
Fax: 314-362-9333

Amy Abrams
Administrative Coordinator
Phone: 314-747-2274
Fax: 314-362-9333

Investigators and Staff

Amy Abrams
Administrative Coordinator
Phone: 314-747-2274
Fax: 314-362-9333

Cara Baczewski
Research Administrator
Phone: 314-747-3705
Fax: 314-362-9333

John DiPersio, MD, PhD
Leader, Project 4
Phone: 314-454-8306
Fax: 314-454-7551

Timothy Graubert, MD
Co-Leader, Project 3
Phone: 617-643-0670

Timothy Ley, MD
Co-Leader, Project 1
Phone: 314-362-8831
Fax: 314-362-9333

Daniel Link, MD
Principal Investigator; Leader, Project 2; Director, Core C; Co-Chair, DRP
Phone: 314-362-8771
Fax: 314-362-9333

J. Philip Miller, PhD
Director, Core B
Phone: 314-362-3617
Fax: 314-362-3728

Lee Ratner, MD, PhD
Chair, DRP
Phone: 314-362-8836
Fax: 314-747-2120

Nancy Reidelberger
SPORE Administrator
Phone: 314-362-9337
Fax: 314-362-9333

Geoff Uy, MD
Co-Chair, CEP; Co-Leader, Project 2
Phone: 314-747-8439
Fax: 314-454-7551

Matthew Walter, MD
Co-Chair, CEP; Co-Leader, Project 3
Phone: 314-362-9409
Fax: 314-362-9333

Mark Watson, MD
Co-Director, Core A
Phone: 314-454-7919
Fax: 314-454-5208

John Welch, MD, PhD
Leader, Project 1
Phone: 314-362-2626
Fax: 314-362-9333

Peter Westervelt, MD, PhD
Director, Core A; Co-Leader, Project 4
Phone: 314-454-8323
Fax: 314-454-7551