Blood Cancers

Current Projects
Andrew M. Intlekofer, MD, PhD

New drugs that target metabolic pathways have shown promise for the treatment of cancer, but the benefits of these drugs have been restricted to rare patients whose cancers have mutations in specific metabolic enzymes. Dr. Intlekofer identified a metabolic pathway whereby subpopulations of genetically identical cancer cells produce a metabolite called L-2-hydroxyglutarate (L-2HG) that induces stem cell-like properties associated with resistance to anti-cancer therapies. He is investigating the mechanisms by which L-2HG regulates the identity and function of cancer stem cells in order to determine whether targeting the L-2HG pathway represents a broadly applicable strategy for treating cancer.

Project title: "Metabolic coupling of the hypoxic niche to stemness"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Ross L. Levine, MD
Cancer Type: Blood, All Cancers
Research Area: Stem Cell Biology
Elise C. Jeffery, PhD

Dr. Jeffery studies “stromal cells” that support the function of blood stem cells in the bone marrow. Cancer treatments such as irradiation and chemotherapy damage the bone marrow, and the repair of this tissue is crucial for the recovery of the blood system. She is characterizing the role of a newly identified factor produced by stromal cells in this rebuilding process. These studies have the potential to enhance our understanding of bone marrow repair, and to identify new methods for improving the recovery of the blood system in cancer patients following irradiation or chemotherapy.

Project title: "Characterizing a new hematopoietic stem cell niche factor"
Institution: University of Texas Southwestern Medical Center
Award Program: Fellow
Sponsor(s) / Mentor(s): Sean Morrison, PhD
Cancer Type: Blood
Research Area: Stem Cell Biology
Michael A. Koldobskiy, MD, PhD

Dr. Koldobskiy studies the ways that cancer cells rely on “epigenetic” modifications, or chemical marks that modify the expression of genes without a change in the genetic sequence itself. Variability of epigenetic marks allows cancer cells flexibility in turning genes on and off, and may account for resistance to treatment. By dissecting the mechanisms of epigenetic modification in pediatric acute lymphoblastic leukemia (ALL), the most common cancer in children, he aims to identify new targets for treatment.

Project title: "DNA methylation stochasticity in pediatric pre-B cell acute lymphoblastic leukemia"
Institution: The Johns Hopkins University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Andrew P. Feinberg, MD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Julia Su Zhou Li, PhD
Project title: "Spatial regulation of the inheritance of genomic abnormalities in cancer cells"
Institution: Ludwig Institute for Cancer Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Don Cleveland, PhD
Cancer Type: Blood, Sarcoma
Research Area: Chromatin Biology
Alexandra Nguyen, PhD

Dr. Nguyen aims to identify the molecular differences between cancer cells and healthy cells, using large-scale genetic approaches in acute myeloid leukemias. Cancer cells exhibit a high degree of diversity in the cellular pathways utilized for survival. Identifying these cellular differences could provide a method to strategically target and kill cancerous cells while minimizing the off-target effects to healthy cells.

Project title: "Defining the cell type specific cell division requirements in acute myeloid leukemias"
Institution: Whitehead Institute for Biomedical Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Iain M. Cheeseman, PhD
Cancer Type: Blood, Other Cancer
Research Area: Cancer Genetics
Sarah Naomi Olsen, PhD

Dr. Olsen is investigating new therapeutic options to treat acute myeloid leukemia (AML), an aggressive form of childhood cancer. One subtype of AML is characterized by a chromosomal translocation involving the MLL (KMT2A) and the AF9 gene, resulting in an abnormal MLL-AF9 fusion protein. Dr. Olsen is targeting the MLL-AF9 fusion protein using a newly developed protein degradation approach. Characterizing the consequences of direct MLL-AF9 degradation will provide important mechanistic insight into how this mutant protein modulates leukemia and help guide the development of combination therapeutic approaches for long-term responses in pediatric AML patients.

Project title: "Targeted degradation of the MLL-AF9 fusion oncoprotein in acute myeloid leukemia"
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Scott A. Armstrong, MD, PhD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Juhee Pae, PhD

Dr. Pae is investigating the regulation of immune B cell proliferation in Germinal Centers (GCs). While this process is critical for bodies to resist infection, it must be carefully regulated. On one hand, not having enough B cells can lead to immunodeficiency and susceptibility to infections. Conversely, inappropriate activation is a major driver of malignant transformation and cancers such as B cell lymphomas. Dr. Pae’s research has the potential to shed light on how lymphomas form and to aid in the rational design of cancer therapeutics.

Project title: "Mechanisms of germinal center B Cell proliferation"
Institution: The Rockefeller University
Named Award: Berger Foundation Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Gabriel D. Victora, PhD
Cancer Type: Blood, Other Cancer
Research Area: Basic Immunology
Maxim Pimkin, MD, PhD

Dr. Pimkin is identifying and characterizing the most critical transcription factors (proteins that regulate the function of genes), called core regulatory circuitries (CRCs), in various types of AML. This will provide new insights into the most critical mechanisms of AML survival and identify new targets for drug development. Preliminary data show that CRCs can accurately and reliably predict critical genes necessary for AML cancer cell survival, suggesting a practical way of identifying potential therapeutic targets. Dr. Pimkin hopes to create a unified understanding of the common and different ways in which AML subtypes arise, as well as create an unprecedented way of predicting common and subtype-specific AML vulnerabilities. 

Project title: "Divergent core transcriptional circuitries highlight context-specific vulnerabilities in AML"
Institution: Harvard Medical School
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Stuart Orkin, MD
Cancer Type: Blood, Pediatric
Research Area: Genomics
Cara A. Rabik, MD, PhD

Dr. Rabik is examining how mutations in the WT1 gene result in methylation changes in acute myeloid leukemia (AML). WT1 recruits the machinery necessary for demethylation to its target genes, ultimately regulating gene expression. When WT1 is mutated, these genes remain methylated and inactive, preventing normal hematopoiesis. She is identifying WT1 target genes and mapping their methylation landscape both in leukemic and normal settings. She will also test drugs designed to cause demethylation to evaluate if these drugs can treat the leukemia caused by mutations in WT1.

Project title: "Determination of the role of WT1 in hematopoiesis and leukemogenesis"
Institution: The Johns Hopkins University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Patrick A. Brown, MD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Marissa Rashkovan, PhD

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, accounting for 10-15% of pediatric and 25% of adult ALL cases. While survival rates have improved with intensified treatment regimens, 25% of pediatric T-ALL cases still relapse because of refractory disease. Furthermore, the intensity of these treatment regimens has led to increased secondary effects in these children later in life. This underscores the need for the development of efficient, targeted and highly specific anti-leukemic therapies to treat T-ALL. Dr. Rashkovan studies a distinct subgroup of immature T-ALL, ETP-ALL, which phenotypically resembles early thymic progenitors (ETPs), has been associated with early relapse, and poor prognosis. There is a particularly urgent need for targeted therapies for ETP-ALL, which is notoriously difficult to treat. She will assess the metabolic vulnerabilities of ETP-ALL in order to propose new, targeted therapies which could be beneficial for the treatment of this high-risk leukemia group.

Project title: "Targeting metabolic vulnerabilities in ETP-ALL"
Institution: Columbia-Presbyterian Medical Center
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Adolfo A. Ferrando, MD, PhD
Cancer Type: Blood, Pediatric
Research Area: Cancer Genetics
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