Blood Cancers

Current Projects
Pavan Bachireddy, MD

Patients with relapsed blood cancers after allogeneic stem cell transplant are often treated with donor lymphocyte infusion (DLI), a type of immunotherapy that boosts the anti-tumor response and aims to induce cancer remission. The success of DLI varies from patient to patient. Dr. Bachireddy aims to investigate the determinants of DLI success and failure by studying the leukemic and immune cells during response to immunotherapy. Careful study of successful anti-tumor immune responses may reveal insights into tumor-immune interactions that may be relevant to predicting patient response to novel immunotherapies in other tumors.

Project title: "Coevolution of tumor and T cell heterogeneity following immunotherapy"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Catherine J. Wu, MD
Cancer Type: Blood
Research Area: Tumor Immunology
Kelly L. Bolton, MD, PhD

Myeloid neoplasms (MN), including acute myeloid leukemia and myelodysplastic syndrome, are lethal blood cancers. The genetic mutations in the blood that lead to MN can occur years before diagnosis and maintain almost normal function before transformation. Certain mutations, including those in the gene IDH2, have been identified as high-risk for developing MN. Individuals with a reduction in the number of mature blood cells (cytopenias) who harbor acquired mutations in their blood, yet do not meet criteria for a cancer diagnosis, have a condition called cytopenias of undetermined significance (CCUS). These individuals almost invariably develop MN. Dr. Bolton will conduct a clinical trial to evaluate whether the IDH2 inhibitor enasidenib can be used as a therapy for CCUS. She will assess mechanisms of resistance and determine whether enasidenib can prevent the development of MN. This represents the first use of genetically targeted therapy for cancer prevention.

Project title: "The use of enasidenib in IDH2-mutated clonal cytopenia of undetermined significance"
Institution: Washington University School of Medicine
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Matthew J. Walter, MD, and Eytan M. Stein, MD
Cancer Type: Blood
Research Area: Genomics
Jessie A. Brown, PhD

Dr. Brown studies acute lymphoblastic leukemia (ALL), an aggressive leukemia and one of the most common malignancies in children and adolescents. Despite significant progress, relapse is associated with high rates of drug resistance and poor prognosis. As a result, relapsed ALL is the leading cause of cancer-related death in children. Dr. Brown will use large-scale genetic (DNA) and transcriptomic (RNA) data and leukemia animal models to dissect how a small number of ALL cells are able to escape the cytotoxic effects of chemotherapy. These cells then undergo genetic and epigenetic changes that allow them to generate resistance to chemotherapy and proliferate, causing relapse of this devastating childhood disease. Understanding this process may lead to novel therapeutic approaches for relapsed ALL.

Project title: "Master regulators of drug resistance in relapsed acute lymphoblastic leukemia" 
Institution: Columbia University
Named Award: Candy and William Raveis Fellow of the Damon Runyon-Sohn Foundation Pediatric Cancer Fellowship Award
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Adolfo A. Ferrando, MD, PhD
Cancer Type: Blood, Pediatric
Research Area: Chemoresistance
Edie I. Crosse, PhD

Dr. Crosse focuses on myelodysplastic syndromes (MDS), blood cancers that occur predominantly in the elderly. These cancers are initiated in the bone marrow when blood stem cells acquire a genetic mutation that causes them to divide and multiply uncontrollably. Through proliferation and acquisition of further mutations, the disease can evolve into acute myeloid leukemia, for which prognosis and survival rate are typically poor. Dr. Crosse aims to identify the specific blood stem cells that are most impacted by the mutation in the early stages of MDS and determine how they contribute to disease progression. The goal is to design therapies that inhibit these mechanisms and halt MDS cancer progression.

Project title: "Determining the role of stem cell heterogeneity in clonal evolution of hematologic malignancy"
Institution: Fred Hutchinson Cancer Research Center
Named Award: Illini 4000 Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Lev Silberstein, MD, PhD, and Irwin D. Bernstein, MD
Cancer Type: Blood, All Cancers
Research Area: Cancer Genetics
Lawrence A. David, PhD

The human gut is home to trillions of microorganisms, collectively called the microbiota, which affect health and disease. For example, in patients receiving hematopoietic stem cell transplantation as treatment for leukemias, lymphomas and other blood cancers, disruptions in the microbiota have been linked to disease relapse, infections and reduced survival. To address these treatment complications, Drs. David and Sung are developing ways to manipulate the microbiota through prebiotics, carbohydrates that a patient can ingest to stimulate the growth and maintenance of various beneficial bacteria. The challenge is that each patient has different microbiota and therefore may respond differently to the same prebiotic therapy. They are developing approaches for personalizing prebiotic treatments for hematopoietic stem cell transplant (HCT) patients based on their individual gut microbiota. After validating their prebiotic personalization with a mouse model, they will test the safety and feasibility of this treatment in a Phase 1 clinical trial with HCT patients.

Project title: "Personalized prebiotics to optimize microbiota metabolism and improve transplant outcomes"
Institution: Duke University
Award Program: Innovator
Cancer Type: Blood
Research Area: Microbiology
Allison L. Didychuk, PhD

Dr. Didychuk is investigating the mechanism by which the Kaposi’s sarcoma herpesvirus (KSHV) co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. This research should reveal insights into this unique mode of transcriptional control. KHSV is an oncogenic virus that causes various cancers including, Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease, in immunocompromised individuals.

Project title: "Viral mimics of host transcription factors in oncogenic herpesviruses"
Institution: University of California, Berkeley
Named Award: The Rhee Family Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Britt Glaunsinger, PhD
Cancer Type: Blood, Other Cancer, Sarcoma
Research Area: Virology
Andrew J. Dunbar, MD

Mutations in the cancer-causing oncogene JAK2 are a hallmark of myeloproliferative neoplasms (MPNs), a blood disorder characterized by over-production of mature blood cells. While currently available JAK2 inhibitors improve symptoms, they are unsuccessful at completely eradicating diseased cells, so remissions are rare. Using genetically engineered mice, Dr. Dunbar will investigate how MPN cells remain dependent on JAK2 signaling for cell growth, and how additional mutations in the epigenome (the proteins involved in regulating gene expression) might contribute to drug resistance. His research aims to identify improved JAK2 inhibitors and lend insight into whether targeting both oncogenic drivers and epigenetic defects could be required for effective therapy. Ultimately, he hopes these findings will translate into better treatments for patients with these cancers.

Project title: "Interrogating functional contribution of JAK2V617F in the maintenance of myeloproliferative neoplasms"
Institution: Memorial Sloan Kettering Cancer Center
Named Award: William Raveis Charitable Fund Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Ross L. Levine, MD
Cancer Type: Blood
Research Area: Cancer Genetics
Timothy J. Eisen, PhD

Dr. Eisen studies how a class of enzymes known as the Tec kinases help to activate the immune response. Two of these kinases, Itk and Btk, are remarkably similar in sequence composition and structure but play distinct roles in immune cells. Dr. Eisen is using high-throughput methods to understand the differences between these enzymes. This work will also aid in the overall molecular understanding of Btk, which is a therapeutic target of B-cell lymphoma and is inhibited by the chemotherapeutic ibrutinib.

Project title: "Mechanistic dissection of Tec kinases in immune-cell signaling"
Institution: University of California, Berkeley
Named Award: David Ryland Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): John Kuriyan, PhD
Cancer Type: Blood
Research Area: Biochemistry
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: "The biology and clinical implications of clonal hematopoiesis in cancer patients"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Benjamin L. Ebert, MD, PhD
Cancer Type: Blood, Other Cancer
Research Area: Cancer Genetics
(Peter) Geon Kim, MD

Blood stem cells, which give rise to various blood cells in the body, acquire mutations with increasing frequency as we age. In the absence of blood cancer development, this state is called clonal hematopoiesis. Up to a quarter of individuals over 60 years old will have recurrent mutations detected in their blood. Recent studies suggest that those with clonal hematopoiesis have an increased risk of developing heart disease and blood cancer, as well as increased levels of inflammatory cytokines – signaling molecules released by immune cells to promote inflammation. Dr. Kim will dissect the mechanisms underlying increased inflammation, which could provide insight into various inflammatory conditions associated with clonal hematopoiesis and potentially elucidate how clonal hematopoiesis progresses into blood cancer.

Project title: "Elucidating the mechanisms of inflammation in clonal hematopoiesis"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Benjamin L. Ebert, MD, PhD
Cancer Type: Blood
Research Area: Cancer Genetics
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