Blood Cancers

Current Projects
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
Birgit Knoechel, MD, PhD

Cancer cells harboring many genetic changes in their DNA often express novel proteins called neoantigens that activate the immune system to recognize and attack the tumor. Based on this mechanism, researchers are developing novel treatments to stimulate the immune system's response against a tumor, but this approach may not work for pediatric cancers that carry few genetic mutations. Dr. Knoechel's research is investigating alternative ways neoantigens can be generated, such as splicing or epigenetic changes, which occur frequently in leukemia and pediatric cancers. She is focusing on T-cell acute lymphoblastic leukemia (T-ALL), an aggressive blood malignancy in children and young adults that frequently stops responding to treatment causing relapse. Her research aims to identify mechanisms of immune "exhaustion" when T-cells stop fighting a tumor, define neoantigens generated by non-genetic mechanisms, and develop novel strategies to target non-genetic neoantigen expression. This research may lead to novel immunotherapy strategies for pediatric tumors.

Project title: "Mechanisms of CD8+ T-cell dysfunction and its therapeutic targeting in T-ALL"
Institution: Dana-Farber Cancer Institute
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Kimberly Stegmaier, MD, and Catherine J. Wu, MD
Cancer Type: Blood
Research Area: Immunotherapy
Julia Su Zhou Li, PhD

Dr. Li focuses on how cells become cancerous when they have an abnormal number of chromosomes or broken parts of a chromosome. The centromere, which joins two arms of a chromosome, is essential for faithful chromosome segregation during cell division and genome stability. When chromosomes fail to be delivered correctly to each new cell, the abnormal chromosomes may form “neocentromeres” which have been discovered in developmental disorders and cancer. Dr. Li is developing tools to examine and manipulate these neocentromeres, which may lead to a better understanding of how cancer cells evolve and potentially novel anti-tumor strategies.

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
Brian B. Liau, PhD

One form of enzyme regulation, called allostery, is critical for integration of different biochemical signals to modulate enzyme structure, activity and function. By combining chemical biology and genome-editing methods, Dr. Liau is pioneering approaches to explore allostery, specifically focusing on DNA methyltransferase enzymes. These enzymes are often disrupted in cancers, including acute myeloid leukemia (AML), but their regulation is not understood. Identifying allosteric mechanisms that regulate DNA methyltransferase function will shed light on the impact of cancer mutations on enzyme function and strategies to pharmacologically modulate their activity. The approaches developed will be broadly expanded to study other enzymes disrupted in cancer and leveraged with synthetic chemistry to enable therapeutics discovery.

Project title: "Investigating allosteric mechanisms regulating DNA methyltransferase enzymes"
Institution: Harvard University
Award Program: Innovator
Cancer Type: Blood
Research Area: Chemical 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
Elli Papaemmanuil, PhD

Cancer survivors are at a higher risk of developing blood cancers than the general population due to the toxic effects of the treatments used to fight their cancer. Therapy-related blood cancers are often resistant to existing drugs and therefore extremely challenging to treat. Contrary to previous thought, recent studies show that the mutations causing these blood cancers can be identified in patients' blood many years before they received therapy. Dr. Papaemmanuil has discovered that the existing mutations alone are not sufficient to cause therapy-related cancer but require the acquisition of additional mutations that affect large segments of the DNA or "allelic imbalances." She will pursue further studies to screen patients and understand the mechanisms of therapy-related blood cancers. These findings will inform clinical strategies of early detection and targeted intervention to better treat this aggressive disease.

Project title: "Biological and clinical implications of allelic imbalances in clonal hematopoiesis and subsequent risk of therapy related leukemia"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Innovator
Cancer Type: Blood, All Cancers
Research Area: Cancer Genetics
Nikit Patel, PhD

Dr. Patel is focusing on hematopoiesis, the process by which stem cells in the bone marrow differentiate into all the blood and immune cells in our bodies. Breakdown of this process is linked to cancers including myelomas and leukemias. Dr. Patel aims to determine critical components driving hematopoiesis by studying this process in different vertebrate animals and comparing evolutionarily conserved regulators. He will then use gene-editing methods to test if these regulators play a role in mammalian hematopoiesis. This work has the potential to identify new therapeutic targets and novel strategies for combatting blood-related cancers.

Project title: "Determining the core genetic regulators of the erythro-myeloid switch"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Allon Klein, PhD
Cancer Type: Blood
Research Area: Systems Biology
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
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