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.

Eligibility

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.

Awards

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 closed. The current application cycle is now closed. The next Request for Applications (RFA) will be announced in March 2015 for funding to begin July 1, 2015. For additional information, please contact Amy Abrams at aabrams@dom.wustl.edu.

2013 Awardees

 

white.jpg   Michael 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.
     
     
j_choi.jpg   Rizwan Romee, MD
Project title: Phase I study of cytokine induced memory-like allogeneic NK cells in patients 

Our group at Washington University School of Medicine has recently described human Cytokine Induced Memory-like (CIML) NK cells which exhibit enhanced anti-leukemia activity. We propose a first-in-humans phase I clinical trial to assess the safety and efficacy of CIML NK cells in patients with relapsed and refractory acute myeloid leukemia (AML).
 
2014 Awardees

 

ley3.jpg   Timothy 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_john.jpg  

John 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.