Search Results
Understanding How Hematopoietic Developmental State Determines Oncogenic KMT2A Fusion Formation and Leukemic Potential
My goal is to understand how cancer-associated gene fusions arise and cause disease. Specifically, I am studying how oncogenic fusions involving the gene KMT2A arise in different hematopoietic cell-types and how developmental context drives the development of leukemia. My long-term goals are to leverage an increased fundamental understanding of leukemogenesis provided by this research to improve treatment and lengthen lifespan for patients with KMT2A fusion-driven leukemias.Modeling LSC heterogeneity at unprecedented resolution in AML
Our goal is to perform high-resolution molecular characterization of human leukemia stem cells (LSCs). We have developed an integrated set of single-cell techniques that will assess transcriptional, genomic, and phenotypic features of primary LSC populations obtained from patients undergoing varying forms of treatment. We expect to create a molecular atlas of primary LSCs that will provide the leukemia research community with a powerful resource for the development of improved therapies.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.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.Therapeutic targeting of AML stem cells 2023
The goal of this SCOR project is to identify and eradicate the root cause of acute myeloid leukemia, the so-called leukemia stem cell (LSC). In the previous cycle of this SCOR grant, we developed two unique strategies, each of which efficiently eradicates LSCs in the laboratory. Going forward, we will expand our scientific efforts to further improve these approaches and also conduct clinical trials to determine whether our approaches to killing LSCs will benefit AML patients.Pan-heme CAR: Anti-CD38 CAR T cells for myeloid, lymphoid and plasma cell malignancies
Our SCOR team has a razor-sharp focus on an exciting new treatment modality for blood cancers: chimeric antigen receptor (CAR) T cells. T cells can be trained to target cancer cells by genetic modification. In fact, previous support from the Leukemia & Lymphoma Society allowed us to successfully develop CAR T cells targeted to CD19, a pan-B cell marker.Memory-like natural killer cells and venetoclax to eradicate measurable residual disease in AML
This proposal is to conduct a phase I (early phase) clinical trial to test whether the combination of the approved targeted therapy venetoclax with memory-like Natural Killer (NK) cells is safe and active in patients with acute myeloid leukemia (AML). Based on laboratory research at Dana-Farber Cancer Institute, we believe that the addition of memory-like NK cells obtained from an haploidentical (‘half matched’) donor will be able to eradicate residual leukemia cells left over after prior venetoclax treatment and hence prevent a future relapse of the disease.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.TCR-like CARs targeting GvL mHAgs for the treatment of post-transplant AML relapse
AML recurrence is a devastating event after allo-HCT. I hypothesize that it could be counteracted through targeting of leukemia-restricted mHAgs via TCR-like CARs. I will identify scFVs recognizing mHAg:HLA complexes using a cell-free nanobody screening platform, and test the anti-leukemia activity and safety of CAR-Ts bearing such scFVs in vitro and in vivo. Through this approach, I will build a library of CAR constructs able to provide population-scale coverage for at-risk allo-HCT patients.Rational therapeutic targeting of oncogenic immune signaling states in myeloid malignancies
Dr. Starczynowski is investigating the role and potential benefit of therapeutic targeting of a protein called UBE2N in acute myeloid leukemia (AML).Targeting the inflammatory GM-CSF pathway in high risk CMML
Chronic myelomonocytic leukemia (CMML) is a rare but poorly understood blood cancer often presenting with crippling inflammatory symptoms that frequently evolves into acute leukemia. In an ongoing clinical trial, we have compelling molecular and clinical data that this disease responds effectively to blockade of GM-CSF with lenzulimab, a well-tolerated and safe antibody, in combination with azacitidine.Studies on clonal hematopoiesis in the 911 WTC first responders
The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to WTC aerosolized dust and gases that contained known and suspected carcinogens including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated furans, dioxins and asbestos. Studies from Dr.Family Support Groups
The Leukemia & Lymphoma Society (LLS) Family Support Groups program gives patients and their families a place to go where they can share information, education and feelings in a comfortable and caring environment. Family Support Groups are for anyone affected by blood cancer and are free. There are currently 230 groups near some of our chapters and in outlying areas, with the number of groups growing each year. Groups generally meet once a month at a library, a local conference room or at LLS's chapters.