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Research We Fund

With hundreds of projects currently underway, we fund scientists through our academic grant programs and biotech partners through our strategic venture philanthropy initiative. Use the filters below to find an LLS-funded project.

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Dr. Yonezawa

Taishi Yonezawa, PhD

Baylor College of Medicine

Houston, Texas
United States

Uncovering mechanisms of DNMT3A stability in hematologic malignancies

DNMT3A is a critical tumor suppressor in hematologic malignancies; DNMT3A protein levels affect both tumor latency and type. DNMT3A is regulated in part by protein stability, but the mechanisms remain incompletely understood. Here, I will dissect the mechanisms that regulate DNMT3A protein turnover using CRISPR screening and genetically engineered mouse leukemia models. This work will reveal whether its stabilization could contribute to a new therapeutic approach for hematologic malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Stewart

Jessica Stewart, PhD

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina
United States

Elucidating the role of FAM72A in EBV-driven B cell lymphomagenesis

This work focuses on characterizing the role of FAM72A in EBV-driven B cell tumorigenesis. This protein is upregulated by EBV during the transformation of B cells and overexpressed in many hematologic cancers. Using a combination of in vitro and in vivo EBV transformation models, high-throughput drug screens, and structural analysis we aim to find small molecules inhibitors that target FAM72A and determine if these drugs can prevent or hinder EBV-associated B cell malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Parsons

Tyler Parsons, PhD

Washington University in St. Louis

St. Louis, Missouri
United States

Mechanisms of Clonal Evolution in the Transformation of MPN to sAML

This research will investigate blood stem cell mutations associated with progression of myeloproliferative neoplasm (MPN) to secondary acute myeloid leukemia (sAML). Our preliminary data suggest that pre-leukemic cells with particular mutations may have a selective advantage in a background of certain MPN subtypes. We will confirm this by utilizing mouse models and both MPN and sAML primary patient samples. Ultimately, we will examine and test inhibition of mechanisms which drive MPN to sAML.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Paczkowska

Julia Paczkowska, PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Characterization and Targeting of Tumor-Associated Monocytes/ Macrophages that Limit the Efficacy of PD-1 Blockade in Lymphoma

Inhibition of the PD-1 exhaustion pathway enables the immune system to attack cancers. PD-1 blockade is now a standard treatment for relapsed classic Hodgkin Lymphoma (cHL) and a component of experimental frontline therapy. In patients with cHL, a newly identified population of monocytes/macrophages limits the efficacy of PD-1 blockade. We will characterize and target these tumor-programmed monocytes/macrophages for therapeutic benefit in patients with cHL and other lymphoid malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Nagler

Adi Nagler, PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

The microbiome-induced immune response role in bronchiolitis obliterans syndrome following allogeneic hematopoietic cell transplantation

The microbiome is increasingly recognized as contributing to chronic graft-versus-host disease (cGVHD). I hypothesize that microbial antigens drive the devastating complication of bronchiolitis obliterans syndrome (BOS). To determine if such antigen targets are at the heart of BOS pathology, I will integrate spatial transcriptomic approaches, immunopeptidome analysis, and direct antigen specificity testing of TCRs from biospecimens collected from preclinical models and patient biospecimens.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Mistry

Jayna Mistry, PhD

The Jackson Laboratory

Bar Harbor, Maine
United States

Bone Marrow Stromal Cell Senescence Induced by Dnmt3a-Mutant Hematopoiesis Drives Clonal Hematopoiesis and Transformation to Myeloid Malignancy

This project focuses on how age-associated clonal hematopoiesis (CH) alters the bone marrow (BM) microenvironment, and whether this promotes transformation of CH to acute myeloid leukemia (AML). I will utilize single cell RNA-seq data, genetic knockout models, and targeted inhibitors to perturb the non-hematopoietic and hematopoietic compartments of a mouse model of CH. The goal is to determine if manipulation of the BM microenvironment can attenuate CH and prevent AML transformation.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Marinaccio

Christian Marinaccio, PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Identification and characterization of genetic factors affecting MLL/KMT2A fusion proteins stability in MLL/KMT2A rearranged leukemias

MLL1/KMT2A rearranged leukemias are the most common blood cancer occurring in children characterized by dismal prognosis. Given the importance of fusion proteins in driving the disease, I will determine factors affecting the fusion protein stability through a CRISPR/Cas9 screening approach in an innovative model system where the MLL fusions are endogenously tagged with a fluorescent protein. This will facilitate development of molecular glue degraders specifically targeting the MLL fusions.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Hall

Trent Hall, PhD

St. Jude Children's Research Hospital

Memphis, Tennessee
United States

Identifying novel regulators of leukemic progression in GATA2-deficiency syndrome

GATA2 deficiency is an inherited pediatric syndrome with a high rate of progression to myeloid malignancy, the mechanisms of which remain largely undefined. Here, we will use our recently generated mouse model, Gata2R396Q, to determine the effects of GATA2 deficiency on hematopoietic function and identify novel drivers of myeloid malignancy via focused CRISPR screens. Our work will provide further insight into the mechanisms driving leukemic progression of this syndrome.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Ren

Kehan Ren, PhD

Northwestern University

Chicago, Illinois
United States

The role of Gasdermin D in the inflammation-driven pathogenesis of myelodysplastic syndromes

We aim to understand the mechanism of how dysregulated Gasdermin D(GSDMD) protein propels the pathogenesis of myelodysplastic syndromes(MDS). With single-cell sequencing and patient-derived xenograft (PDX) mouse models, we want to provide pre-clinical grade data to support the concept of inhibiting GSDMD as an effective therapeutic approach in the treatment of MDS. We expect to see the great beneficial effects of GSDMD inhibition in MDS mouse models and PDX mouse models using FDA-approved drugs.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2025
Dr. Sugio

Takeshi Sugio, MD, PhD

Stanford University

Palo Alto, California
United States

An integrated liquid biopsy framework for surveillance of residual disease and host immune status of T-cell lymphomas

I aim to develop an accurate disease monitoring system and identify immunologic determinants of development and progression in T-cell lymphoma (TCL). I will integrate noninvasive liquid biopsy methods by high-throughput sequencing. I will study blood samples at various milestones, including pre-diagnostic, diagnostic/baseline, and post-treatment specimens during the natural history of TCL. Using these novel tools and unique specimens, my goal is the development of effective therapies for TCL.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2025
Dr. Montefiori

Lindsey Montefiori, PhD

St. Jude Children's Research Hospital

Memphis, Tennessee
United States

Molecular basis and new therapeutic strategies in lineage ambiguous leukemia

Lineage-ambiguous leukemias are high-risk blood cancers with unclear biologic basis and suboptimal treatment options. Here, I will identify the cell of origin of lineage ambiguous leukemia and investigate new therapeutic strategies through in vitro and in vivo experimental modeling approaches and preclinical drug studies in patient-derived xenografts. These studies will clarify the cellular and molecular alterations driving lineage ambiguity and advance a new, rational therapeutic approach.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2025
Dr. Zhang

Christine Zhang, PhD

Washington University in St. Louis

St. Louis, Washington
United States

Deciphering the role of p53 signaling in NPM1-mutant AML

NPM1c and TP53 mutations are exclusive in acute myeloid leukemia (AML) despite both being commonly present in patients, suggesting a fitness disadvantage for cells with co-occurring mutations. However, the mechanisms underlying this exclusivity have not been explored. This project will utilize novel models to dissect the importance of TP53 signaling in NPM1c+ (pre)-leukemic stem cells. Generated results may highlight therapeutic opportunities for improved risk management of NPM1c+ AML patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2025
Dr. Liu

Yiman Liu, PhD

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania
United States

Investigating the impact of hotspot mutations in a chromatin reader on leukemogenesis

The goal of this proposal is to investigate the consequence of the chromatin reader eleven-nineteen-leukemia (ENL) gain-of-function mutations in the pathogenesis of leukemia. Our studies leverage the expertise in the molecular and chromatin biology of chromatin reader in leukemia utilizing mouse model, high resolution image, epigenomic and transcriptomic approaches. Our goal is to understand how chromatin reader contributes to cancer development, progression, and therapeutic outcome.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2025
Dr. Collins

Cailin Collins, MD PhD

Stanford University

Palo Alto, California
United States

Investigating the role of preleukemia duration and clonal burden in progression to AML

The development of acute myeloid leukemia (AML) is preceded by a “preleukemic” phase in which mutated hematopoietic stem cells expand due to a fitness advantage. Our work uses prospective models and analysis of patient samples to study how the duration of preleukemia and how the preleukemic clonal burden affect progression to AML. Results of our studies will shed new light on AML pathogenesis and help guide clinical management of preleukemic conditions such as clonal hematopoiesis.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Will

Britta Will, PhD

Albert Einstein College of Medicine

Bronx, New York
United States

Therapeutically actionable molecular safeguards in leukemic stem cells

Our research program’s goal is to identify therapeutically actionable pathways in pre-leukemic and leukemic stem cells in myeloid malignancies. We specifically dissect molecular circuits governing stem cell self-renewal and differentiation, how these change during aging, and contribute to leukemic stem cell evolution and maintenance. Accomplishing this work will enable the rational design of curative intervention and perhaps even prevention strategies for patients with myeloid malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Wan

Liling Wan, PhD

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania
United States

Epigenetic Mechanisms in Acute Myeloid Leukemia

The goal of this project is to investigate the role of the epigenetic regulator Eleven-Nineteen-Leukemia (ENL) and its cancer mutations in acute myeloid leukemia (AML). Our studies leverage the expertise in chromatin biology, functional genomics, and AML modeling, as well as unique chemical compounds and mouse models. Results from this project will provide novel biological insights into our understanding of AML pathogenesis and facilitate the development of novel epigenetic therapies.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Pietras

Eric Pietras, PhD

University of Colorado Denver, Anschutz Medical Campus

Denver, Colorado
United States

Targeting the pathogenic 'fire triangle' of inflammation, metabolism and mutations in myeloid leukemogenesis

My lab is focused on understanding the pathogenic interplay between oncogenic mutations, chronic inflammation and aberrant metabolism as a driver of the evolutionary processes that culminate in lethal myeloid malignancies. We leverage mouse models and human patient samples to establish modalities for targeting this interplay throughout disease pathogenesis. My long-term goal is to improve patient outcomes by establishing therapies that prevent and/or delay evolution to acute leukemia.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Doulatov

Sergei Doulatov, PhD

University of Washington

Seattle, Washington
United States

Modeling and targeting leukemic transformation of human hematopoietic stem cells

Our research seeks to understand how ordered acquisition of oncogenic mutations transforms human hematopoietic stem cells into myeloid malignancies. We leverage patient-derived induced pluripotent stem cells and primary normal and malignant stem cells to study how mutation cooperation drives leukemic progression in vitro and in vivo. Our long-term goal is to identify disease mechanisms and develop targeted therapies to eradicate malignant stem cells.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. de Smith

Adam de Smith, PhD

University of Southern California

Los Angeles, California
United States

Leveraging Susceptible Populations and Unique Resources in a Pathway to Prevention of Childhood Acute Lymphoblastic Leukemia

The focus of my research is to understand the causes and early-life origins of acute lymphoblastic leukemia (ALL). We use a two-pronged approach: 1) conducting epidemiological studies of ALL in susceptible populations to understand genetic predisposition, and 2) investigating the in utero origins of ALL across subtypes. Our goals are to identify children at the highest risk of developing ALL through genetic screening and to lay the groundwork for precision prevention strategies.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Maude

Shannon Maude, MD PhD

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania
United States

Improving CAR T-cell Therapy Efficacy in Acute Lymphoblastic Leukemia by Optimizing Design and Placement

Pediatric acute lymphoblastic leukemia (ALL) that is resistant to standard therapy is a challenge that has been partially overcome by T-cell therapy, yet relapse still occurs in up to 50%. We are conducting two clinical trials that test a next-generation T-cell therapy and the first incorporation of T-cell therapy into initial therapy. These trials will inform future development and the optimal place for this therapy with the goal of improving cure rates for children with very high risk ALL.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Kahn

Justine Kahn, MD

Columbia University Medical Center

New York, New York
United States

Leveraging cancer registries, clinical trials, and community partnerships to address disparities in pediatric, adolescent, and young adult lymphoma

I aim to identify drivers of pediatric and adolescent/young adult lymphoma disparities so that targeted health equity interventions can be developed. Integration of large datasets, systematic collection of social determinants data in clinical trials, and collaboration with patient advocates will: a) create new population-based resources to study lymphoma outcomes; b) establish a novel framework for equity research in lymphoma clinical trials; and c) identify real-world targets for intervention.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Ahn

Inhye Ahn, MD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Clinical and molecular determinants of CLL eradication with targeted combination therapy

The genomic architecture of residual CLL and molecular determinants of disease progression after targeted combination therapy are unknown. In a phase 2 study of zanubrutinib and venetoclax in CLL, I will investigate the depth of response and genomic changes using cellular and circulating tumor DNA. Data generated from this proposal will provide foundational evidence to develop genomic markers for non-invasive monitoring of treatment response and precise prediction of outcome.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2028
Dr. Bjelosevic

Stefan Bjelosevic, PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Metabolic Regulation of Leukemic Cell Fate

Cell-intrinsic metabolic processes are dysregulated in acute myeloid leukemia (AML) and can act to sustain an oncogenic state of differentiation arrest. Using AML cell lines and patient-derived material grown in sophisticated liquid culture medium that mimics human plasma, we will perform metabolically focused in vitro and in vivo CRISPR-Cas9 screens to reveal metabolic regulators of AML cell fate that can be exploited via dietary or pharmacologic intervention as a novel therapeutic strategy.

Program: Career Development Program
Project Term: Start Date: July 1, 2023 End Date: June 30, 2026
Dr. Crews

Leslie Crews, PhD

University of California, San Diego

San Diego, California
United States

Inflammation-responsive mechanisms of malignant stem cell generation and eradication in multiple myeloma

The focus of my research is to elucidate the core molecular regulators of malignant stem cell generation in multiple myeloma. My approach addresses the tumor cell-intrinsic versus niche-dependent mechanisms of myeloma regeneration by exploring transcription factor expression and stemness profiles within single cells from primary samples and patient-derived models. The central goal of my research is to uncover novel therapeutic strategies and translate these into new myeloma treatments.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Hamilton

Mark Hamilton, MD PhD

Stanford University

Stanford, California
United States

Cell-free DNA analysis of persistent CAR T-cell populations in humans

The focus of this research project is to understand how therapeutic chimeric antigen receptor (CAR) T-cells mediate long-term remission of diffuse large B-cell lymphomas. I will use cell free DNA collected from patient plasma to understand if there is an association of CAR T-cell persistence and long-term tumor remission. The goal of this research is to define how CAR T-cells suppress tumors over time to develop better CAR T-cells in the future.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: May 24, 2024
Dr. Strati

Paolo Strati, MD

The University of Texas MD Anderson Cancer Center

Houston, Texas
United States

A Phase I/II Study of the Combination of ALX148, Rituximab and Lenalidomide in Patients with Indolent and Aggressive B-cell Non-Hodgkin Lymphoma

SIRPα+ macrophages mediate resistance to lenalidomide in B-cell lymphoma, limiting the activity of immunotherapy for these patients. Therefore, we propose a phase I/II study, investigating the safety and efficacy of ALX148, a novel fusion protein of the SIRPα binding domain, in combination with rituximab and lenalidomide in patients with B-cell lymphoma. We hypothesize that this combination will be safe and effective, providing a chemotherapy-free option for these patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Wen

Hong Wen, PhD

Van Andel Research Institute

Grand Rapids, Michigan
United States

Investigating and targeting the histone acetylation reader protein ENL in acute leukemias

Leukemia often results from aberrant gene expression caused by epigenetic alterations. Previously we discovered a novel histone acetylation reader domain in the ENL protein and demonstrated that this domain is essential for the survival of a wide range of acute leukemias, making it an attractive therapeutic target. We will develop specific inhibitors of ENL activity in acute leukemias and will use mouse models to define the role of ENL mutations identified in patients in leukemogenesis.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Herranz

Daniel Herranz, PharmD, PhD

Rutgers University

New Brunswick, New Jersey
United States

Therapeutic exploitation of novel mouse models and metabolic interventions in leukemia

Our research program aims to gain a deeper understanding of the pathobiology of T-ALL and HSTL.

To this end, we will use novel mouse models, cutting-edge techniques and comprehensive genetic, pharmacological and metabolic interventions. In addition, we will perform unbiased experiments to identify novel therapeutic targets.

Our goal is to uncover new tools and targets for the treatment of T-ALL and HSTL, which could be used for the benefit of patients in the short/mid-term.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. McNerney

Megan McNerney, MD PhD

The University of Chicago

Chicago, Illinois
United States

Genomic interrogation of high-risk myeloid neoplasms to identify new therapies

The long-term goal of my research program is to improve the outcomes for patients with high-risk myeloid blood cancers, particularly those with loss of chromosome 7 or CUX1. We are tackling this question using an arsenal of innovative methods and tools, including mouse models, human cells and patient samples, and state-of-the-art technologies to examine the cancer cell genome. Accomplishing this work will reveal new treatments and strategies for preventing blood cancers from arising.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Yang

Yibin Yang, PhD

Fox Chase Cancer Center

Philadelphia, Pennsylvania
United States

Analysis and therapeutic targeting of the immune regulatory and ubiquitination pathways in Anaplastic Large Cell Lymphoma and Hodgkin Lymphoma

My lab is focused on the immune regulatory mechanisms and ubiquitin-dependent machinery in lymphoma. We have established multiple high-throughput screening technologies and animal models to rapidly and accurately identify critical pathways that are suitable for targeted therapy and immunotherapy. Gaining insight into the pathological roles of these pathways can lead to improved understandings of the molecular circuitry that drives lymphoma pathogenesis and provide novel therapeutic strategies.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Maxson

Julia Maxson, PhD

Oregon Health & Science University

Portland, Oregon
United States

Targeting the interplay between signaling and transcriptional dysfunction in myeloid leukemias

Our research program is focused on understanding the intersection between signaling and transcriptional dysfunction in myeloid leukemias. We leverage murine models, cell lines and human samples to uncover how biological context shapes the manifestation of oncogenic programs at the molecular level. Our long-term goal is to harness this knowledge to identify multipronged therapeutic strategies that improve outcomes for patients with myeloid malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Lindsley

Coleman Lindsley, MD PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Genetic pathways of myeloid transformation and treatment response

Our central goal is to improve clinical outcomes in patients with myeloid malignancies through developing an enhanced mechanistic understanding of disease. We use multiomic analyses of primary patient samples combined with complementary laboratory models using mice and cell lines to generate and test our hypotheses. The results of our studies will help improve patient outcomes by identifying strategies to mitigate risk of disease progression/relapse and treatment toxicity.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Busino

Luca Busino, PhD

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania
United States

Relevance of ubiquitin dependent proteolysis in Diffuse Large B-cell lymphoma

The goal of this proposal is to investigate the significance of genes of the ubiquitin proteasome system (UPS) that are mutated in Diffuse Large B-cell Lymphoma (DLBCL). Our studies leverage the expertise in the molecular modeling of the UPS in the pathogenesis of DLBCL utilizing mouse models, patient derived xenotransplant (PDX) and cell lines. Our goal is the understanding of how genetic mutations contribute to disease development, progression and therapeutic outcome.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Takahashi

Koichi Takahashi, MD

The University of Texas MD Anderson Cancer Center

Houston, Texas
United States

Understanding the clonal origin, evolution, and progression of myeloid malignancies

The overarching focus of my research is to understand the clonal origin, evolution, and progression of myeloid malignancies and biological and clinical factors that influence the process. We tackle this question by analyzing patient samples with integrated approach combining single-cell omics, evolutionary genetics, and computational analytics. The ultimate goal of our research is to develop clinical strategies for early detection, prevention, and treatments of myeloid malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. LeBlanc

Thomas LeBlanc, MD, MA, MHS, FAAHPM

Duke University

Durham, North Carolina
United States

Patient Experience Research and Palliative Care Integration in Malignant Hematology

My research aims to improve the patient and caregiver experience of blood cancer care. To achieve this, I conduct trials of integrated palliative care interventions. Palliative care improves patient and caregiver outcomes for those with solid tumors, but less is known about its role in hematology. My research aims to design and implement integrated palliative care interventions in blood cancer settings, to improve the patient and caregiver experience of illness, regardless of treatment outcome.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Philips

Tycel Phillips, MD

Beckman Research Institute of the City of Hope

Duarte, California
United States

Stratified treatment of newly diagnosed MCL based on the presence or absence of high risk features utilizing non-cytotoxic agents.

We believe that regimens without chemotherapy can induce significant and durable remissions in patients with Mantle cell lymphoma (MCL). We will confirm this hypothesis by conducting two clinical trials stratified by the presence or absence of high risk features. We will utilize BH3 profiling and MRD testing to assist with predicting treatment response and remission. Our goal is to verify the efficacy of our regimen and prove the utility of BH3 profiling and MRD testing in outcome prediction.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: September 30, 2027
Dr. Mehta-Shah

Neha Mehta-Shah, MD

Washington University School of Medicine in St. Louis


United States

Predictors of response to therapy in A051902, a US Intergroup study of duvelisib+CHO(E)P vs CC-486+CHO(E)P vs CHO(E)P in peripheral T-cell lymphoma

We are evaluating if adding duvelisib or azacitidine to standard chemotherapy increases the complete remission rate compared to chemotherapy alone in peripheral T-cell lymphoma. We believe that adding novel agents to chemotherapy will most benefit lymphomas with a T-follicular helper phenotype. We will also study if tests for lymphoma cells in the blood can predict outcomes. We hope these novel therapies will cure more patients and we can identify who is most likely to benefit from them.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Shah

Nirav Shah, MD, MSHP

Medical College of Wisconsin

Milwaukee, Wisconsin
United States

Improving Bispecific CD20/CD19 CAR T-cell Therapy to Overcome Resistance Mechanisms in B-cell Malignancies

The objective of this proposal is to improve bispecific anti-CD20/anti-CD19 CAR T-cell activity and persistence by understanding impact of cell manufacturing parameters on final engineered CAR-T product and determining resistance mechanisms in relapsing patients. We will analyze patient apheresis, final CAR-T product, and peripheral blood samples from subjects enrolled on an ongoing clinical trial (NCT04186520). Data from these studies will advance CAR T-cell therapies for lymphoma patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Jain

Nitin Jain, MD

The University of Texas MD Anderson Cancer Center

Houston, Texas
United States

Combination Targeted Therapy in Chronic Lymphocytic Leukemia

Targeted therapies have replaced chemoimmunotherapy in chronic lymphocytic leukemia (CLL). We previously reported that combined BTK inhibitor (ibrutinib) and BCL2 antagonist (venetoclax) is highly synergistic. In this proposal, we will conduct a phase II trial of combined non-covalent BTK inhibitor (pirtobrutinib) with venetoclax and obinutuzumab in patients with untreated CLL with primary endpoint of marrow MRD. We will perform BH3 profiling and scRNAseq and correlate with clinical outcomes.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Kristinsson

Sigurður Kristinsson, MD PhD

University of Iceland

Reykjavík
Iceland

Early Detection and Intervention in Smoldering Multiple Myeloma: population-based screening and treatment; Edit-SMM

We build on the success from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, where over 80,000 consented to a nationwide screening for MM precursors. A unique cohort of patients with SMM diagnosed in iStopMM will be followed by clinical evaluation, linking to central health data registries, using novel biomarkers, and in-depth genetics. With precision early treatment we aim to induce a paradigm shift leading to improved quality of life and potentially a cure for MM.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2027
Dr. Saygin

Caner Saygin, MD

The University of Chicago

Chicago, Illinois
United States

Deciphering the interplay between apoptotic and signaling pathways to target T-lineage acute lymphoblastic leukemia

T-ALL is an aggressive leukemia with limited treatment options. T-ALL cells resist to dying by suppressing their suicide pathways. BH3 mimetics reactivate the suicide mechanisms to induce cell death. We showed that these drugs are effective in T-ALL, but acquired resistance is due to the activation of growth-promoting signaling pathways. The proposed experiments will decipher the relationship between growth and death pathways, identifying unique combination therapies to improve disease outcomes.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2025
Dr. Morelli

Eugenio Morelli, MD

Candiolo Cancer Institute

Turin
Italy

Defining the Biologic and Therapeutic Significance of the Novel Long Noncoding RNA MYND in Multiple Myeloma

Long non-protein coding RNAs (lncRNAs) are fundamental for proper cell function, but their purpose is poorly understood in multiple myeloma. To systematically identify myeloma-promoting lncRNAs, we integrated gene expression profiling of myeloma patients with high-throughput loss-of-function studies in cell lines. Moreover, we optimized strategies to antagonize myeloma-promoting lncRNAs, thus paving the way to developing lncRNA inhibitors as the next generation of therapy.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2024
Dr. Baeten

Jeremy Baeten, PhD

Washington University in St. Louis

St. Louis, Washington
United States

Combined targeting of ATR and replicative stress in TP53-mutated AML

This research will test a promising new drug combination in acute myeloid leukemia (AML) carrying TP53 gene mutations, which is resistant to chemotherapy and has a median survival of less than 5 months. Our preliminary data show that TP53-mutated AML is selectively sensitive to the combination of an ATR inhibitor and decitabine. We will confirm activity of this novel drug combination using mouse models of leukemia and human AML samples and explore mechanisms of responsiveness.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2024
Dr. Booth

Christopher Booth, PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Mechanisms of Pathogenesis by MYB Fusions in Blastic Plasmacytoid Dendritic Cell Neoplasm

The transcription factor MYB has long been associated with leukemia, but how it contributes to disease is poorly understood. Fusions of MYB to other proteins, causing MYB activation, are found in patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), but rare in other leukemias. I am using recently developed techniques to gain insight into how MYB fusions cause BPDCN. This will enable both new treatments for BPDCN and better understanding of the role of MYB in other leukemias.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2024
Dr. Luo

Qingyu Luo, MD PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Defining PIK3R5-related PI3K gamma dependency as a novel therapeutic target in blood cancers including BPDCN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive blood cancer without adequate treatment. In a genome-wide CRISPR interference screen, BPDCN was highly dependent on the PI3Kγ pathway and specifically the PIK3R5 adaptor subunit. A subset of leukemias may share this vulnerability. We will interrogate the mechanism of this unique dependency and integrate PIK3R5/PI3Kγ targeting with leukemia therapy. Our goal is to provide novel treatments for PIK3R5-dependent malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2025
Dr. Kramer

Frederike Kramer, PhD

Brigham and Women’s Hospital

Boston, Massachusetts
United States

Investigating the Role of ASXL1 Mutations in CALR-mutated Myeloproliferative Neoplasms

My research focuses on myeloproliferative neoplasms (MPN) and the mutations that drive the progression of these blood cancers. Currently, I am investigating mutations in the gene ASXL1, which are associated with a poor prognosis. I am using mouse models and patient-derived cells to determine how ASXL1 mutations mediate epigenetic changes in MPN. My goal is to identify ways of targeting the pathological mechanisms caused by ASXL1 mutation, resulting in new treatment strategies for patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2022 End Date: June 30, 2025
Dr. Olszewski

Adam Olszewski, MD

Rhode Island Hospital

Providence, Rhode Island
United States

Mosunetuzumab with lenalidomide augmentation as first-line therapy for patients with follicular and marginal zone lymphoma

Dr. Olszewski’s trial will examine mosunetuzumab as a first-line treatment for follicular and marginal zone lymphomas—slow-growing types of B-cell lymphoma which remain incurable using current therapies. Mosunetuzumab is a “bispecific antibody” that can trigger an immune attack of patients’ own cancer-killing T-cells against the lymphoma. Dr. Olszewski team will look for characteristics that predict complete responses when this novel immunotherapy is applied as first-line treatment.

Program: Career Development Program
Project Term: Start Date: April 1, 2022 End Date: March 31, 2027
Dr. Catherine Smith

Catherine Smith, MD

University of California San Francisco

San Francisco, California
United States

SHP2 and BCL2 Inhibition in Acute Myeloid Leukemia

The goal of our work is to use a “bench to bedside and back” approach to develop new treatments for patients with relapsed/refractory AML. Through genetic analysis of patients who relapse or do not respond to standard and investigational treatments, we discover potential resistance mechanisms. In the lab, we test novel drugs and identify new drug targets that may address these resistance mechanisms when used in combination with other therapies. The overall goal of our research program is to improve treatment options and survival of patients with refractory AML.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2026
Andrew Lane

Andrew Lane, PhD, MD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): understanding disease biology to improve therapy

We focus on blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive blood cancer with limited treatment options and poor outcomes. We want to understand what causes the disease, develop laboratory tools, and identify new treatments and ways to overcome therapy resistance. We have translated our discoveries to clinical trials. Our goal is to continue this bench to beside approach to develop the next generation of BPDCN therapies that improve survival and minimize treatment toxicity.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2026
Simona Colla

Simona Colla, PhD

The University of Texas MD Anderson Cancer Center

Houston, Texas
United States

Validation of Critical 1q21 Vulnerabilities in multiple myeloma

In previous studies of recurrently amplified 1q21 genes in myeloma, we identified ILF2 as a modulator of the DNA repair pathway, which promotes adaptive responses to genotoxic stress. Thus, ILF2 may have clinical utility as a biomarker of aggressive myeloma and blocking the ILF2-mediated repair signaling may enhance the effectiveness of current DNA-damaging agent-based therapies. We are seeking to determine the feasibility of therapeutically targeting ILF2 with antisense nucleotides and identify DNA repair effectors whose loss of function induces synthetic lethality in ILF2-depleted myeloma.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Frederick Locke

Frederick Locke, MD

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida
United States

Clinical investigation to improve efficacy of CAR-T Cell Therapy for Large B Cell Lymphoma

We are investigating new interventions that could improve the effectiveness of CAR T-cell therapy for lymphoma. A clinical trial will test radiation immediately followed by CAR-T. Larger lymphoma tumors are less likely to respond to CAR-T and we expect that radiation could reduce the amount of tumor, leading to improvement in responses. We will also conduct a series of trials to determine the effectiveness of vaccinations before and after CAR T cell therapy, and if anti-cancer vaccines could improve outcomes.

Program: Career Development Program
Project Term: Start Date: January 1, 2021 End Date: December 31, 2025
Rong Lu

Rong Lu, PhD

University of Southern California

Los Angeles, California
United States

Dissecting the heterogeneity of leukemic and pre-leukemic clonal expansion to identify genes associated with leukemia relapse and genesis

My research investigates the heterogeneity of leukemic and pre-leukemic clonal expansion to identify genes associated with leukemia relapse and genesis. Contrary to conventional studies analyzing cell mixtures, my research uniquely probes the specific cells underlying leukemia development. We expect to identify the key cellular and molecular events that drive leukemia onset and relapse. These findings will help improve diagnosis and can serve as new therapeutic targets for treating leukemia.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Daniel Lucas

Daniel Lucas, PhD

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio
United States

Cellular Crosstalk In The Normal And Malignant Bone Marrow

We want to understand how leukemia inhibits blood production as this is one of the main causes of death in leukemia patients. We use new microscopy techniques developed by our group to image—for the first time—all types of blood cells and how they are eradicated by leukemia cells. Identification of the mechanisms through which leukemia inhibits blood production will be the foundation for new studies to develop drugs to maintain normal blood levels and prevent death in leukemia patients.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2026
Jeffrey Magee

Jeffrey Magee, PhD, MD

Washington University School of Medicine in St. Louis

St. Louis, Missouri
United States

Neonatal origins of pediatric AML

Coming soon.

Program: Career Development Program
Project Term: Start Date: July 1, 2021 End Date: June 30, 2026
Kasey Leger

Kasey Leger, MD

Seattle Children's Hospital

Seattle, Washington
United States

Cardioprotective Strategies and Cardiotoxicity Prediction in Children with Acute Myeloid Leukemia

We seek to reduce the adverse cardiac effects of chemotherapy in pediatric AML patients. We are assessing markers of heart function and injury to compare two clinical strategies for prevention of chemotherapy-induced heart injury. We are also developing a tool using these markers of heart function to characterize a child’s risk for cardiac dysfunction, which is critical to guiding safe chemotherapy delivery. By reducing the toxicity of therapy on the heart we hope to optimize delivery of effective chemotherapy and contribute to long-term leukemia cure without the burden of life-threatening heart disease during survivorship.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Shannon McKinney-Freeman

Shannon McKinney-Freeman, PhD

St. Jude Children's Research Hospital

Memphis, Tennessee
United States

Improving hematopoietic stem cell transplantation by defining novel regulators of engraftment

Blood-forming stem cells are routinely transplanted into patients to treat blood cancers. We discovered that multiple members of the GASP (G-protein coupled receptor Associated Sorting Proteins) family inhibit the function of blood-forming stem cells during transplantation. Our goal is to determine exactly how GASP family members inhibit these critical cells in order to inform our efforts to improve the efficiency of blood stem cell transplantation.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Dan Landau

Dan Landau, PhD, MD

Weill Cornell Medicine

New York, New York
United States

Defining the role of DNA methylation modifier mutations in reshaping blood differentiation topology

Coming soon.

Program: Career Development Program
Project Term: Start Date: July 1, 2021 End Date: June 30, 2026
Rajni Kumari

Rajni Kumari, PhD

Albert Einstein College of Medicine

Bronx, New York
United States

Role of HLX in leukemia induction and maintenance

We and others have shown how HLX overexpression keeps blood cells more immature by blocking their differentiation and promoting their proliferation, a characteristic which is inherent to AML. However, whether there is a causative role of HLX in the induction of AML is still unclear. Hence, the aim of my study is to better understand, using genetically engineered mice models, retroviral models, and human AML patient samples, how HLX drives AML at molecular level. This study will uncover potential therapeutic strategies for AML treatment in future.

Program: Career Development Program
Project Term: Start Date: April 1, 2021 End Date: March 31, 2024
Alison Moskowitz

Alison Moskowitz, MD

Memorial Sloan Kettering Cancer Center

New York, New York
United States

JAK/STAT inhibition as a therapeutic strategy in T-cell lymphoma

Given the high rate of JAK/STAT pathway dysregulation in T-cell lymphomas, we aim to develop new personalized therapies with JAK inhibitors for T-cell lymphoma. Our recent study with ruxolitinib (a JAK inhibitor) showed that activation of a parallel oncogenic pathway, PI3-kinase, predicts for poor response to ruxolitinib in T-cell lymphoma. Building upon this observation, we are assessing whether dual inhibition of JAK and PI3-Kinase will lead to higher efficacy in T-cell lymphoma.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Daisuke Nakada

Daisuke Nakada, PhD

Baylor College of Medicine

Houston, Texas
United States

Synergistic targeting of metabolic and epigenetic vulnerabilities in leukemia stem cells

Our lab is focused on identifying unique features that distinguishes acute myeloid leukemia (AML) stem cells from normal blood-forming stem cells. The cells that make more AML cells than others are called AML stem cells, and these cells need to be eradicated to achieve deep therapeutic responses. We believe targeting metabolism may achieve this goal and found strategies to target AML stem cell metabolism without harming normal stem cells. We hope that our study will lead to improved therapies against AML targeting metabolism to achieve deep remission with little toxicity.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Lakshmi Navak

Lakshmi Nayak, MD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

PD1 blockade alone and in combination with BTK/ITK inhibition in patients with refractory and recurrent primary central nervous system lymphoma

We study a rare and aggressive brain cancer called primary central nervous system lymphoma (PCNSL). We are using an emerging knowledge of the genetic basis of PCNSL to develop novel clinical trials exploring the use of targeted and immunotherapy agents in PCNSL patients. These trials include assessment of the activity of a PD-1 inhibitor by itself and in combination with a BTK inhibitor in PCNSL patients, as well as identifying any mechanisms of treatment resistance that may develop. The goal of our clinical research is to enhance survival and improve neurologic function in PCNSL patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Thomas Koehnke

Thomas Koehnke, MD

Board of Trustees of the Leland Stanford Junior University

Palo Alto, California
United States

The role of truncating ASXL1 mutations in disease initiation and progression of human myeloid malignancies

N/A

Program: Career Development Program
Project Term: Start Date: July 1, 2021 End Date: June 30, 2024
Eirini Papapetrou

Eirini Papapetrou, PhD, MD

Icahn School of Medicine at Mount Sinai

New York, New York
United States

Studying the biology and therapeutic vulnerabilities of leukemia stem cells using AML-iPSCs

Acute myeloid leukemia (AML) is an aggressive blood cancer that still lacks effective therapies. Our goal is to identify therapeutic vulnerabilities for long-lasting remission or cure of AML by targeting the leukemia stem cells (LSCs), the cells that maintain the disease and re-grow it upon relapse. To this end, we leverage unique model systems of AML LSCs that we have developed using induced pluripotent stem cell (iPSC) technology. Our study may open new avenues for the therapy of AML.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Alex Kentsis

Alex Kentsis, PhD, MD

Memorial Sloan Kettering Cancer Center

New York, New York
United States

Targeting kinase-dependent dysregulation of transcription factor control in acute myeloid leukemia

Defining mechanisms of dysregulated gene control are central to understanding cancer and the development of effective therapies. Our research is focused on the mechanisms of gene control dysregulation in acute myeloid leukemia (AML), a refractory form of blood cancer that affects both children and adults. Using new methods for manipulating proteins, we are defining essential mechanisms by which AML cells enable cancer-causing gene expression. This work also allowed us to develop new drugs to specifically block this in cancer, but not healthy cells. Ongoing work aims to define precise mechanisms of cancerous gene control and develop definitive treatments for its control.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Jonas Jutzi

Jonas Jutzi, PhD, MD

Brigham and Women’s Hospital

Boston, Massachusetts
United States

Unfolding selective pathway dependencies of CALR mutated myeloproliferative neoplasms

The goal of this study is to selectively eradicate blood cancer cells carrying mutations in a gene called calreticulin. Genes and corresponding proteins required for cancer cell survival but not for the survival of healthy cells will first be targeted in mice, both genetically and by using drugs. Validated drugs will then be tested on patient samples. This study will lay the foundation to the development of tailored treatments for patients with calreticulin-mutated blood cancer.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2024
Hao Jiang

Hao Jiang, PhD

University of Virginia

Charlottesville, Virginia
United States

Dissecting the role of a key epigenetic modulator in Mixed Lineage Leukemia

We study how a protein called Dpy30 controls blood cancers by regulating chromatin, the physical structure where our genes reside. We study how this protein controls addition of a specific chemical group onto chromatin, thereby regulating expression of genes for leukemia in cells and animals. We are also developing chemicals to inhibit Dpy30’s activity in leukemia. We hope to better understand the role of Dpy30 in leukemia and identify Dyp30-inhibiting chemicals for leukemia treatment.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Daniel Pollyea

Daniel Pollyea, MD

University of Colorado Denver, Anschutz Medical Campus

Aurora, Colorado
United States

Targeting Leukemia Stem Cells in the Clinical Setting: The Development of A Comprehensive Program

My focus is to develop a program in which novel therapies targeting leukemia stem cells (LSCs) are tested in clinical trials. This is achieved via partnership with laboratory-based colleagues who identify vulnerabilities in LSCs. Once recognized, we find or develop drugs to exploit these weaknesses through clinical trials for acute myeloid leukemia patients. The goal is to bring forward new therapies that result in deep and durable responses, which also have the potential to cure this disease.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Zhijian Qian

Zhijian Qian, PhD

University of Florida

Gainesville, Florida
United States

The role of FOXM1 downregulation in the development of clonal dominance in del(5q) MDS

Our research focuses on identifying the molecular mechanism underlying the development of a dominant population of abnormal stem cells in myelodysplastic syndrome (MDS) patients. We will employ mouse genetic models and MDS patient samples to elucidate the role of FOXM1 in the development of a dominant population of abnormal stem cells in vivo. This research program may lead to the identification of new effective therapeutic strategies for the treatment of early stages of MDS patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Christiane Querfeld

Christiane Querfeld , PhD, MD

Beckman Research Institute of the City of Hope

Duarte, California
United States

Unraveling the mechanisms of immune checkpoint dysfunction in cutaneous T cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a disfiguring, incurable malignancy profoundly affecting patients’ appearances, quality of life, and relationships. Standard treatments only benefit 30% of patients with limited duration. Rather than focusing on the tumor alone, we target the adjacent tumor microenvironment, which nourishes tumor growth. We have begun a clinical trial of durvalumab, which is an inhibitor of the checkpoint protein receptor PD-L1. We are currently investigating how immune checkpoint proteins together with the immune booster lenalidomide affect CTCL growth. This research will benefit not only those with CTCL but many other cancers.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Peng Ji

Peng Ji, PhD, MD

Northwestern University

Chicago, Illinois
United States

The role of Plek2 in the pathogenesis of myeloproliferative neoplasms

Our research focuses on the study of a novel therapeutic target, named Plek2, in the development of myeloproliferative neoplasms (MPNs). MPNs can progress to leukemia and there are currently no cures. We use animal models and patient samples to study how elevated levels of Plek2 causes the disease and identify approaches to suppress the function of Plek2. Our goal is to use the knowledge from this study to develop novel therapies to treat MPNs.

Program: Career Development Program
Project Term: Start Date: July 1, 2017 End Date: June 30, 2022
Caron Jacobson

Caron Jacobson, MD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

CAR T-cell therapy in central nervous system (CNS) lymphoma: a study in safety and efficacy and a model in which to study mechanisms of neurotoxicity

CAR T-cells are highly effective in lymphoma but limited by a profound and potentially fatal toxicity involving the central nervous system (CNS). Little is known about how CAR T-cells eliminate lymphoma cells in the CNS nor how this therapy causes toxicity. I will study CAR T-cells in patients with CNS lymphomas with the goal of expanding CAR T-cell indications. I will also examine serial blood and CNS samples to understand neurologic toxicity to inform new therapies to control this toxicity.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2026
Kerry Rogers

Kerry Rogers , MD

The Ohio State University

Columbus, Ohio
United States

Improving BTK Inhibitor Therapy in Chronic Lymphocytic Leukemia Through Rational Combination Strategies

Ibrutinib is a targeted oral treatment for CLL that is safe and highly effective, however it must be given indefinitely which leads to chronic side effects and allows resistance to develop. We are conducting two clinical trials that add a second drug to ibrutinib to eliminate the remaining leukemia or ibrutinib-resistant leukemia cells. If these trials are successful, people taking CLL with or without resistance may be able to stop treatment in remission after taking an ibrutinib combination.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Dr. Ito

Keisuke Ito, PhD, MD

Albert Einstein College of Medicine

Bronx, New York
United States

Targeting mitophagy of leukemia stem cells for therapy

Enhancing the commitment of leukemia stem cells (LSCs) is a promising therapeutic strategy against blood cancer, but tracking the division pattern of individual cells has proved difficult. We have established a novel technical regimen to assess the behavior of individual LSCs and their cell fate in vivo. Genetic mouse models and mouse models engrafted with leukemia patient samples are also used. Our project seeks to elucidate the role of mitophagy in the control of LSC division balance, which may facilitate new therapy targeting these cells.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Rizwan Romee

Rizwan Romee, MD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Cytokine induced memory-like NK cell immunotherapy to target post transplant relapse

Coming soon.

Program: Career Development Program
Project Term: Start Date: July 1, 2021 End Date: June 30, 2026
Michael Savona

Michael Savona, MD

Vanderbilt University Medical Center

Nashville, Tennessee
United States

Manipulation of cell fate in myeloid disease

Apoptosis is a normal cellular process of getting rid of extra cells that is co-opted by cancer cells to enhance their own survival, and we aim to better understand this process in myelodysplastic syndromes (MDS). Pevonedistat (PEV) is a novel therapy presumed to function, in part, through its effects on apoptosis. Our clinical trial will combine PEV with the standard of care therapy for MDS, azacitidine, in order to keep cancer cells from hijacking apoptosis, and we will study patient samples to match responses with molecular changes in the cancer cells. We seek to determine the suitability of this approach for MDS, and the ability to predict which patients may respond to PEV-based therapy.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Alex Herrera

Alex Herrera, MD

Beckman Research Institute of the City of Hope

Duarte, California
United States

Novel combination strategies to enhance brentuximab vedotin efficacy in relapsed/refractory Hodgkin Lymphoma

New, non-chemotherapy treatments that use a patient’s own immune system have transformed the treatment of Hodgkin lymphoma (cHL). Typically used in patients with cHL that is resistant to standard treatment, these immune therapies can control the disease for months to years. However, in the long run, most patients will not be cured and will have immunotherapy-resistant cHL. My research evaluates strategies for reversing resistance to brentuximab vedotin (BV) immunotherapy for cHL by combining BV with other treatments in clinical trials.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Michael Green

Michael Green, PhD

The University of Texas MD Anderson Cancer Center

Houston, Texas
United States

Investigating the role of CREBBP mutations and epigenetic crosstalk in B-cell lymphoma

We seek to understand the genetic and epigenetic etiology of B-cell lymphoma and how deregulation of normal epigenetic programs perturb developmental programs and immune interactions. We approach this using a variety of genomic technologies to interrogate primary human tumors, CRISPR-engineered cell lines, patient-derived xenograft models and transgenic mouse models with different genetic lesions. We hope to understand how genetic and epigenetic changes associated with B-cell lymphoma create dependencies or characteristics that can be targeted through rational therapeutic interventions to improve patient outcomes.

Program: Career Development Program
Project Term: Start Date: October 1, 2020 End Date: September 30, 2025
Mitchell Geer

Mitchell Geer, PhD

New York University School of Medicine

New York, New York
United States

Role of ERK isoforms in normal hematopoiesis and leukemia

Current therapies for cancers driven by “RAS/ERK’ pathway mutations, such as juvenile myelomonocytic leukemia (JMML), are either high risk (bone marrow transplant) or ineffective (targeted inhibitors). We have identified a unique dependency of JMML cell growth for a group of ERK targets, which are not required for normal blood cell growth. We are investigating this further and aim to identify the ERK targets responsible, which may provide new drug targets to treat JMML and other cancers.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2022
Alfred Garfall

Alfred Garfall, MD

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania
United States

Enhancing CAR T cell therapy for multiple myeloma

My overall focus is to improve CAR T cell therapy for multiple myeloma. Our clinical trial uses CAR T cells targeting BCMA as first line therapy for high-risk multiple myeloma to assess whether early use of CAR T cells is safer and more effective than use in patients with relapsed disease. Half of patients will also receive CAR T cells targeting CD19 to assess whether this can improve the duration of response to anti-BCMA CAR T cells. Our goal is to evaluate whether early use of CAR T cells is a safer and more effective way to use CAR T cells for multiple myeloma patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Maria Figueroa

Maria "Ken" Figueroa, MD

University of Miami

Coral Gables, Florida
United States

Epigenetic Deregulation of Hematopoietic Cells with Aging and Disease

Our lab is focused on understanding how age-related epigenetic deregulation contributes to driving the functional decline of the hematopoietic system we see as we age. We are using genome-wide sequencing approaches to understand the changes in human hematopoietic stem and progenitor cells (HSPC) with aging at epigenomic level, along with in vitro and in vivo modeling of key changes that we hypothesize are the responsible drivers of the aging decline phenotype. Our overarching goal is to identify key drivers of functional HSPC decline to ultimately develop methods for modulating these drivers and achieve HSC rejuvenation.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Areej El-Jawahri

Areej El-Jawahri, MD

Massachusetts General Hospital

Boston, Massachusetts
United States

Randomized Trial of a Sexual Dysfunction Intervention for Hematopoietic Stem Cell Transplant Survivors

Our goal is to improve sexual function and quality of life for patients with blood cancers undergoing hematopoietic stem cell transplantation. We will conduct a clinical trial to evaluate whether a multi-component intervention to address sexual health and intimacy concerns can improve sexual function and satisfaction as well as quality of life and mood in hematopoietic stem cell transplant survivors. We will also explore whether improvement in sexual function leads to improvement in quality of life in this population. By developing an innovative and potentially scalable model of care to address sexual health issues, we aim to improve the quality of life and survivorship care for patients with blood cancers.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Lei Ding

Lei Ding, PhD

Columbia University Medical Center

New York, New York
United States

Targeting the interaction of leukemia stem cells with their niche to treat myelofibrosis

Bone marrow scar formation (fibrosis) is a hallmark of myelofibrosis and contributes significantly to the disease progression. We use mouse genetics to model myelofibrosis and understand the cellular and molecular makeup of the diseased microenvironment. We aim to understand the composition and alteration of the bone marrow microenvironment in myelofibrosis. This may provide novel therapeutic targets for myelofibrosis.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Courtney DiNardo

Courtney DiNardo, MD

The University of Texas MD Anderson Cancer Center

Houston, Texas
United States

A precision-based all-oral combination of venetoclax, oral decitabine, and IDH1/2 targeted inhibition for patients with IDH1 or IDH2 mutated AML

My ultimate goal is to develop more effective, better tolerated, and individualized treatment for patients with AML. This project focuses on AML patients with IDH1 or IDH2 mutations, with a clinical trial evaluating a combination of three agents which are effective in IDH-mutated AML. While these therapies are not curative on their own, my hope is that this combination will lead to a practice changing all-oral, outpatient, and well-tolerated curative strategy for patients with IDH-mutated AML.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2026
Alexey Danilov

Alexey Danilov, PhD, MD

Beckman Research Institute of the City of Hope

Duarte, California
United States

Overcoming ibrutinib resistance in mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive blood cancer which affects about 3,000 individuals in the United States annually. Despite advances of novel therapies in blood cancers, MCL remains incurable, and patients ultimately succumb to disease. We seek to evaluate longitudinal samples from patients with MCL treated with novel therapies to understand the mechanisms of drug resistance. We identify novel targets, with a particular focus on protein turnover pathways, to overcome drug resistance and improve survival of patients with MCL.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Jaehyuk Choi

Jaehyuk Choi, PhD, MD

Northwestern University

Chicago, Illinois
United States

Identification of novel therapeutic strategies for aggressive subtypes of CTCL

Coming soon.

Program: Career Development Program
Project Term: Start Date: July 1, 2021 End Date: June 30, 2026
Jianhua Yu

Jianhua Yu, PhD

Beckman Research Institute of the City of Hope

Duarte, California
United States

All-in-one for myeloma: a single therapy to combine CAR T cells and bispecific antibodies to engage both innate and adaptive immune responses

This project is designed to develop a novel cell therapy to treat relapse/refractory multiple myeloma (MM), an incurable cancer. We target BCMA, a protein highly expressed on MM compared to normal cells, with CAR T cells that also secrete a bispecific antibody that can engage all cytolytic cells, including various endogenous T cells, natural killer (NK) cells, and NKT cells to kill MM cells. We aim to complete all preclinical studies so that the therapy is ready for future clinical studies.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Sisi Chen

Sisi Chen, PhD

Memorial Sloan Kettering Cancer Center

New York, New York
United States

Aberrant LZTR1 and RIT1 signaling as a driver of clonal hematopoietic disorders

Our research focuses on a novel mechanism of RAS protein regulation via the protein LZTR1, which is altered in leukemia and hinders the effectiveness of leukemia therapies. We will utilize mouse models and functional genomic studies to uncover how altered RAS degradation drives leukemia and identify novel drug targets. This effort will help us identify the clinical impact of alterations in this novel RAS pathway in patients and potential means to improve leukemia treatment.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2024
Grant Challen

Grant Challen, PhD

Washington University in St. Louis

St. Louis, Missouri
United States

Synergism of cell-intrinsic and cell-extrinsic factors in the clonal evolution of pre-malignant HSCs

We study the mechanisms of clonal hematopoiesis (CH), a process by which mutations provide hematopoietic stem cells (HSCs) with a fitness advantage. CH can precede the development of blood cancer. We use cutting-edge techniques to understand the effects of these mutations on HSC behavior. Our long-term goal is to identify ways to inhibit the growth of these mutant HSCs while sparing normal HSCs in people with CH. This may someday provide a blood cancer prevention method by eliminating the cells which carry the initial cancer-driving mutations.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Jason Butler

Jason Butler, PhD

Hackensack Meridian Health

Edison, New Jersey
United States

Modulating Signaling Pathways in Endothelial Cells to Abate Leukemic Progression

We seek to elucidate the mechanisms by which aging of the vascular system contributes to the decline in blood stem cell function and leads to diseases such as hematopoietic malignancies. We have developed novel model systems that have led to the discovery of rejuvenation factors that can restore the functional capacity of an aging blood and vascular system. These studies lay the foundation for the development of therapeutic strategies to not only rejuvenate an aged blood system, but to also give a competitive advantage to non-malignant blood cells while directly targeting cancer cells following chemotherapy regimens commonly utilized to treat hematological malignancies.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Amin Sobh

Amin Sobh, PhD

University of Florida

Gainesville, Florida
United States

Investigating the Role of Adenylate Kinase 2 in Multiple Myeloma

The goal of my research is to characterize the role of the cellular metabolic regulator AK2 in multiple myeloma (MM) pathogenesis and therapy resistance. A series of molecular, biochemical, and functional assays will be performed using laboratory models to define the basis of MM cell dependence on AK2 and elucidate its role in MM progression and drug resistance. This work will highlight novel metabolic vulnerabilities in MM that can be targeted to further enhance therapeutic outcomes.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2024
Sarah Tasian

Sarah Tasian, MD

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania
United States

Precision Medicine Inhibitor and Immunotherapy Approaches for High-Risk Childhood Leukemias

Dr Tasian’s scientific passion is successful development of precision medicine therapies for high-risk childhood leukemia. Her translational laboratory research program focuses upon investigation of kinase inhibitors and chimeric antigen receptor (CAR) T cell immunotherapies in childhood ALL and AML using primary patient specimens and patient-derived xenograft models. Through her laboratory and clinical research, she aspires to improve cure rates and minimize toxicities for children with leukemia.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2026
Samuel Taylor

Samuel Taylor, PhD

Albert Einstein College of Medicine

Bronx, New York
United States

Pharmacological inhibition of the transcription factor PU.1 as a novel treatment for acute myeloid leukemia

Transcription factors are components of a cell which control our genetic information and are known to have altered function in diseases such as Acute Myeloid Leukemia (AML). I am investigating how we can better understand and use novel transcription factor drugs as therapy for AML. This involves using CLICK-chemistry drug localization studies and creating transcription factor occupancy maps of the genome. Overall, my work will help to understand the inner workings of transcription factors in disease and provide a new therapeutic option for the treatment of AML.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2021
Jennifer Trowbridge

Jennifer Trowbridge, PhD

The Jackson Laboratory

Bar Harbor, Maine
United States

Discovery of Aging-Driven Mechanisms Causing Clonal Hematopoiesis (CH) and its Progression to Hematological Malignancy

My research focuses on why and how risk of acute myeloid leukemia (AML) increases with aging. Studying naturally aged mouse models in combination with mice engineered to express mutations commonly found in human blood stem cells with aging, we are investigating whether certain inflammatory factors that increase during aging increase the risk of leukemia. My goal is to identify biomarkers to assess risk of AML development in aging individuals and define new therapeutic targets to prevent AML.

Program: Career Development Program
Project Term: Start Date: January 1, 2021 End Date: December 31, 2025
Nathan Ungerleider

Nathan Ungerleider, PhD

Tulane University School of Medicine

New Orleans, Louisiana
United States

EBV promotes Burkitt's lymphoma progression through microprocessor sequestration.

This proposal aims to understand the molecular mechanisms underlying response to AZA therapy in MDS, as a basis for developing more effective therapies. A ribonucleotide, AZA’s effects on RNA remain unknown. Here, we will investigate the impact of in vivo AZA therapy on RNA alternative splicing and DNA demethylation in MDS patients. Secondly, we will investigate whether AZA treatment exposes neoepitopes in the dysplastic cells of patients, which could be exploited for cancer immunotherapy in MDS

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2023
Juliette Bouyssou

Juliette Bouyssou, PhD

Dana-Farber Cancer Institute

Boston, Massachusetts
United States

Understanding sex differences in myeloid and dendritic differentiation and function to target high-risk leukemias including BPDCN

There are widely recognized but unexplained sex differences in cancer incidence and outcomes, including in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive leukemia that occurs over 3 times more frequently in men. We aim to identify male-female differences in plasmacytoid dendritic cells, the blood cell involved in BPDCN, to better understand this disease. Our goal is to use what we learn to improve the treatment of BPDCN and related blood cancers for both men and women.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2022
Dane Vassiliadis

Dane Vassiliadis, PhD

The University of Melbourne

Parkville, Victoria
Australia

Targeting non-genetic mechanisms of therapeutic resistance in Acute Myeloid Leukaemia

Drug resistance in AML can develop via a non-genetic process which remains poorly understood. Using our novel cellular barcoding technology that can trace the growth of thousands of cancer cells, our research will identify genes that are switched on or off in AML cells that lead to drug resistance and relapse. This work will reveal the factors underpinning non-genetic drug resistance that may be targeted with new drugs to prevent relapse and ultimately improve quality of life and survival.

Program: Career Development Program
Project Term: Start Date: October 1, 2021 End Date: September 30, 2024
Therese Vu

Therese Vu, PhD

University of Colorado Denver, Anschutz Medical Campus

Aurora, Colorado
United States

Evaluating a novel collaboration between NOTCH1 and MLL1 for improved targeted treatments in T-ALL

Most T cell acute lymphoblastic leukemia (T-ALL) patients respond to chemotherapy, however many relapse with limited therapy options. To address this problem, we are utilizing a newly-developed human T-ALL system to study two potential therapy targets (NOTCH1 and MLL1) and their interaction, to determine if they can be co-inhibited to eradicate disease. Since compounds that inhibit NOTCH1 and MLL1 are already in development, this novel combination strategy could lead to clinical approval sooner.

Program: Career Development Program
Project Term: Start Date: January 1, 2021 End Date: December 31, 2023
G. Greg Wang

G. Greg Wang, PhD

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina
United States

Decipher and Target AML Cell Dependency on Epigenetic Mutations

The goal of our program aims to understanding the general roles of DNA methylation machineries in epigenetic regulation and cancerous transformation seen in hematological cancers. Routinely, we take a set of integrated biochemical, genomics, oncology, and medicinal chemistry approaches to tackle the broad and critical questions in this field. Our findings shall not only promote current understanding of how hematological malignancies occur but also help develop novel therapeutic approaches.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Jennifer Woyach

Jennifer Woyach, MD

The Ohio State University

Columbus, Ohio
United States

Overcoming BTK Inhibitor Resistance in Chronic Lymphocytic Leukemia

Coming soon.

Program: Career Development Program
Project Term: Start Date: April 1, 2021 End Date: March 21, 2026
Jian Xu

Jian Xu, PhD

The University of Texas Southwestern Medical Center

Dallas, Texas
United States

Functional and mechanistic roles of BCAA metabolism in the progression of myeloproliferative neoplasms

The processes that control the progression of myeloproliferative neoplasms to leukemic transformation remain largely unknown. We have developed genetic mouse models that recapitulate leukemia progression in humans. We aim to discover new regulators and pathways controlling the propagation of leukemia stem cells as targetable vulnerabilities. Our study promises to provide critical insights into developing new and generalizable therapies to selectively eliminate leukemia stem cells.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024
Amer Zeidan

Amer Zeidan, MBBS

Yale University

New Haven, Connecticut
United States

The use of immune checkpoint inhibitors to improve outcomes of patients with myeloid malignancies

We are testing whether the immune checkpoint inhibitor pembrolizumab can improve outcomes of patients. In MDS, we showed that entinostat reduces the number and activity of immune suppressive cells, thereby making the cancer susceptible to the killing effect of pembrolizumab. We are now testing this combination in a clinical trial. In CML, many patients cannot completely clear the disease despite tyrosine kinase inhibitor (TKI) therapy due to inability of their immune system to eradicate all CML cells. We therefore designed a clinical trial to augment the TKI impact on CML cells by adding pembrolizumab.

Program: Career Development Program
Project Term: Start Date: July 1, 2018 End Date: June 30, 2023
Arash Alizadeh

Arash Alizadeh, PhD, MD

Board of Trustees of the Leland Stanford Junior University

Palo Alto, California
United States

Refining Molecular Risk Prediction & Individualized Lymphoma Therapy Using Circulating Tumor DNA

My group studies variation in clinical outcomes of patients with aggressive lymphomas and tries to capture the underlying basis for this variation. We then integrate insights from our studies into molecular prediction tools that inform the probable outcomes of individual patients when treated with therapeutic regimens that are currently available. We hope to build precise risk models that have high predictive value for clinical outcomes of patients with lymphoma. Our goal is to use these models to inform therapeutic trials of novel strategies to improve the outcomes of blood cancer patients.

Program: Career Development Program
Project Term: Start Date: July 1, 2019 End Date: June 30, 2024