Blood Cancers

Current Projects
Anupam K. Chakravarty, PhD

Dr. Chakravarty [HHMI Fellow] is investigating heritable physical structures, called higher order assemblies, formed upon overexpression of RNA binding proteins. RNA binding proteins are consistently overexpressed in multiple cancers. His research will illuminate the mechanism of assembly formation and its role in altering gene regulation, thereby suggesting novel avenues to potential therapeutic intervention.

Project title: "Investigating the phenomenon of epigenetic inheritance mediated by non-amyloid protein aggregates"
Institution: Stanford University School of Medicine
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Daniel F. Jarosz, PhD
Cancer Type: Blood, All Cancers
Research Area: Epigenetics
Jaehyuk Choi, MD, PhD

Cutaneous T cell lymphoma (CTCL) is an incurable cancer of the immune T cells in the skin. In advanced disease, the cells escape into the blood, the lymph nodes, and at times the visceral organs. Patients with advanced disease eventually succumb to a combination of tumor burden and disease-related immunosuppression. Dr. Choi [Doris Duke-Damon Runyon Clinical Investigator] has recently used next generation sequencing to identify gene mutations that he hypothesizes are important for CTCL pathogenesis. He will molecularly dissect how these gene mutations alter signaling pathways in CTCL, using human models and patient samples. His ultimate goal is to identify novel therapeutic strategies that selectively target CTCL cancer cells, hastening the development of a cure for this intractable disease.

Project title: "Identification of genetic basis of altered T cell receptor signaling in cutaneous T cell lymphoma"
Institution: Northwestern University
Named Award: Doris Duke-Damon Runyon Clinical Investigator
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Stephen D. Miller, PhD, and John D. Crispino, PhD
Cancer Type: Blood
Research Area: Cancer Genetics
Stacy L. Cooper, MD

Dr. Cooper focuses on developing novel therapies for acute myeloid leukemia (AML), which has an approximately 50% mortality rate. Her work focuses on C/EBPalpha, a protein that is decreased in more than half of all AML patients. By determining how the production of this protein is regulated, she aims to understand the mechanisms for its reduction in leukemia and to develop strategies to target C/EBPalpha as a novel therapy for AML.

Project title: "The Cebpa +37kb enhancer is a critical target of transformation in acute myeloid leukemia"
Institution: The Johns Hopkins University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Alan D. Friedman, MD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Kyle G. Daniels, PhD

Dr. Daniels aims to improve the ability of engineered T cells to kill cancer. Specifically, his goal is to understand how signaling events during T cell activation determine the therapeutic properties of activated T cells. He uses synthetic immunology techniques and computational methods to search for synthetic receptors that confer desired functions upon T cells. Ultimately, he hopes to design and create receptors that improve the ability of T cells to proliferate, persist, recruit other immune cells, and kill cancer cells.

Project title: "Controlling T cell signaling and fate choice using synthetic receptors"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Wendell Lim, PhD
Cancer Type: Blood
Research Area: Immunotherapy
Marco L. Davila MD, PhD

The goal of cancer immunotherapy is to adapt the natural components of the immune system to eradicate cancer. T cells are a type of immune cell highly evolved to detect and eradicate diseased cells. Dr. Davila is developing a novel treatment approach that involves genetic engineering of T cells as a safe and effective immunotherapy for blood cancers such as B cell lymphoma. This research has great potential because by genetically targeting T cells to a cancer, the T cell can be forced to recognize a cancer as diseased and initiate direct tumor killing, as well as activate a widespread and long-lived immune response against the cancer.

Project title: "The development and clinical translation of an armored CAR T cell therapy for immune-resistant B cell malignancies"
Institution: H. Lee Moffitt Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Michel Sadelain, MD, PhD and Claudio Anasetti, MD
Cancer Type: Blood
Research Area: Immunotherapy
Michael W. Drazer, MD

Leukemia is, for some patients, an inherited disease that may affect multiple individuals within a single family. Similar to other diseases such as inherited breast cancer, we now understand that specific genes may increase an individual's risk for developing leukemia over the course of his or her lifetime. While an increasing number of genes involved in inherited leukemia have been identified, the underlying molecular mechanisms that contribute to the development of leukemia and other blood cancers are less well understood. Some individuals with inherited blood cancers develop abnormal blood conditions years before actually developing overt leukemia. Dr. Drazer aims to better understand the molecular mechanisms that cause these abnormal blood conditions to transition into leukemia. The goal of this work is to apply these findings to inform future therapies for patients with blood cancers.

Project title: "Defining leukomogenic mechanisms in hereditary hematologic malignancies"
Institution: The University of Chicago
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Lucy A. Godley, MD, PhD
Cancer Type: Blood
Research Area: Cancer Genetics
Christopher J. Gibson, MD

Christopher’s research centers on the earliest steps whereby normal cells transform into abnormal cells with the potential to become cancer. He will focus on better understanding the first steps of the process by which normal blood cells become lymphomas, cancers that are generally thought to arise from blood cells that have already committed to becoming lymphocytes, an important component of the immune system. He hypothesizes, however, that some lymphomas actually arise from earlier hematopoietic stem cells (HSCs). He will interrogate this hypothesis by studying a cohort of lymphoma patients who also have detectable genetic mutations in HSCs that are known to be associated with blood cancers – a condition known as clonal hematopoiesis of indeterminate potential, or CHIP – to determine whether the mutations in the HSCs were the earliest events in the development of the patients’ lymphomas. Having a better understanding of lymphomas’ cellular basis will hopefully allow new insights into their clinical behavior and therapeutic vulnerabilities.

Project title: Elucidating the connection between clonal hematopoiesis and lymphoma in humans
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Benjamin L. Ebert, MD, DPhil
Cancer Type: Blood, Other Cancer
Research Area: Cancer Genetics
Casey A. Gifford, PhD

Dr. Gifford [HHMI Fellow] aims to identify and define the roles for DNA binding proteins that can manipulate DNA conformation in the nucleus. DNA is maintained in an ordered conformation that contributes to control of gene expression and cellular identity. She will employ next-generation sequencing approaches and human induced pluripotent stem cells to better understand the mechanisms of this process. Her goal is to understand why the loss of function or aberrant expression of these DNA binding proteins leads to cancer.

Project title: "Dissecting the role of pioneer transcription factors in cancer progression"
Institution: Gladstone Institutes
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Deepak Srivastava, MD
Cancer Type: Blood, All Cancers
Research Area: Chromatin Biology
Alejandro Gutierrez, MD

It remains unclear why some patients' tumors can be cured with chemotherapy, whereas other tumors that appear to be nearly identical are completely chemoresistant. Dr. Gutierrez focuses on this issue in a particularly high-risk subset of T-cell acute lymphoblastic leukemia, a disease that most commonly affects older children and young adults. His goals are to define the molecular basis of resistance to conventional chemotherapy in patients with this disease, and to leverage this knowledge to develop a therapeutic strategy to restore chemosensitivity. Ultimately, this could lead to significant improvements in clinical outcome for these patients.

 

Project title: "Mechanisms and therapeutic targeting of EZH2-dependent chemoresistance in T-ALL"
Institution: Boston Children's Hospital
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Stuart Orkin, MD and Anthony Letai, MD, PhD
Cancer Type: Blood
Research Area: Chemoresistance
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
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