A5019671129- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Cutaneous lymphoproliferative disorders research
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Toxin Mechanisms and Immunotoxins
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Viral-associated cancers and disorders
- Histiocytic Disorders and Treatments
- Lung Cancer Treatments and Mutations
- Multiple Myeloma Research and Treatments
- Lipid metabolism and disorders
- Protein Degradation and Inhibitors
- Chemokine receptors and signaling
- CRISPR and Genetic Engineering
- interferon and immune responses
- Eosinophilic Disorders and Syndromes
- Cytokine Signaling Pathways and Interactions
- Vascular Tumors and Angiosarcomas
- Bone health and treatments
Harvard University
2015-2024
Brigham and Women's Hospital
2015-2024
University of Minnesota Medical Center
2024
University of Minnesota
2018-2024
Mapp Biopharmaceutical (United States)
2022
Dana-Farber Cancer Institute
2016-2019
Dana-Farber Brigham Cancer Center
2017-2019
University of Virginia
2019
Lemuel Shattuck Hospital
2018
Bristol-Myers Squibb (Switzerland)
2017
Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood otherwise healthy adults. We hypothesized that patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at time ASCT would be associated with increased risk myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related neoplasm (TMN), other adverse outcomes. Methods performed whole-exome sequencing on...
Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell that arises around breast implants. The optimal management this disease has not been established. goal study to evaluate the efficacy different therapies used in patients with BI-ALCL determine an treatment approach.In study, we applied strict criteria pathologic findings, assessed used, and conducted clinical follow-up 87 BI-ALCL, including 50 previously reported literature 37 unreported. A Prentice,...
Abstract Somatic mutations in calreticulin (CALR) are present approximately 40% of patients with myeloproliferative neoplasms (MPN), but the mechanism by which mutant CALR is oncogenic remains unclear. Here, we demonstrate that expression alone sufficient to engender MPN mice and recapitulates disease phenotype CALR-mutant MPN. We further show thrombopoietin receptor MPL required for CALR-driven transformation through JAK–STAT pathway activation, thus rendering CALR-transformed hematopoietic...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the antiapoptotic protein BCL2 and uniformly sensitive to inhibitor venetoclax, as measured by direct cytotoxicity, apoptosis assays, dynamic BH3 profiling. Animals bearing patient-derived xenografts had disease responses improved survival after venetoclax treatment in vivo Finally, we...
PURPOSE Smoldering multiple myeloma (SMM) is a precursor condition of (MM) with 10% annual risk progression. Various prognostic models exist for stratification; however, those are based on solely clinical metrics. The discovery genomic alterations that underlie disease progression to MM could improve current models. METHODS We used next-generation sequencing study 214 patients SMM. performed whole-exome 166 tumors, including 5 serial samples, and deep targeted 48 tumors. RESULTS observed...
Abstract Background: Parkinson's disease (PD) is heterogeneous and age at onset may define variation in clinical phenotype. Most previous studies have used various cut‐offs been based on case series. Methods: We studied the association between features of 358 community‐based regional patients with PD. Results: Tremor presentation twice as common those over 64 years compared to under 45 (early PD ‐ EOPD) becomes more increasing (p values for trend ≤ 0.004). Dystonia affects 60% EOPD, shows a...
Highlights•CXCR4 mediates extra-medullary multiple myeloma (MM)•CXCR4 enhances EMT-like phenotype acquisition in MM•Ulocuplumab inhibits MM cell dissemination and EMT MMSummaryExtra-medullary disease (EMD) (MM) is associated with poor prognosis resistance to chemotherapy. However, molecular alterations that lead EMD have not been well defined. We developed bone marrow (BM)- EMD-prone syngeneic lines; identified epithelial-to-mesenchymal transition (EMT) transcriptional patterns were...
Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated (NICD1) FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain detects neoepitope created proteolytic cleavage event activates NOTCH1. Following validation using xenografted cancers normal with known patterns activation, applied test to tumors linked dysregulated Notch...
T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell myeloid malignancies, there few preclinical models TCLs, which has hampered the development effective therapeutics. Here we establish characterize TCL. We identify multiple vulnerabilities that targetable currently available agents (e.g., inhibitors JAK2 or IKZF1) demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). show...
Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas subset of develops tumor mass or lymph node involvement (LNI). The aim this study to describe the pathologic features nodes from BI-ALCL and assess prognostic impact LNI. Clinical findings histopathologic were assessed in 70 BI-ALCL. LNI was defined by histologic demonstration ALCL nodes. Fourteen (20%) had LNI,...
The challenge of eradicating leukemia in patients with acute myelogenous (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested combination DNA methyltransferase inhibitor decitabine together immune checkpoint ipilimumab for AML/myelodysplastic syndrome (MDS) either allogeneic hematopoietic stem cell transplantation (HSCT) or HSCT-naïve setting. Integrative...
Tumours most often arise from progression of precursor clones within a single anatomical niche. In the bone marrow, clonal progenitors can undergo malignant transformation to acute leukaemia, or differentiate into immune cells that contribute disease pathology in peripheral tissues
MRE11 functions in several aspects of DNA metabolism, including meiotic recombination, double-strand break repair, and telomere maintenance. Although the purified protein exhibits 3' to 5' exonuclease endonuclease activities vitro, Mre11 is implicated resection duplex ends vivo. The mre11-H125N mutation, which eliminates nuclease Mre11, causes an accumulation unprocessed breaks (DSBs) meiosis, but no defect processing HO-induced DSBs mitotic cells, suggesting existence redundant activities....
Summary Extramedullary disease ( EMD ), defined as an infiltrate of clonal plasma cells at anatomic site distant from the bone marrow, is uncommon manifestation multiple myeloma. Six hundred and sixty‐three consecutive patients with myeloma who underwent stem cell transplantation between January 2005 December 2011 were assessed for presence . A cohort 55 biopsy‐proven was identified, comprising 8·3% total study population. present time diagnosis in 14·5% cases relapse 76% patients. The most...
Abstract Integrin β3 is critical for tumor invasion, neoangiogenesis, and inflammation, making it a promising cancer target. However, preclinical clinical data of integrin antagonists have demonstrated no benefit or worse outcomes. We hypothesized that could affect immunity evaluated tumors in mice with deletion macrophage lineage cells (β3KOM). β3KOM had increased melanoma breast growth tumor-promoting M2 macrophages decreased CD8+ T cells. antagonist, cilengitide, also enhanced function....
Langerhans cell histiocytosis (LCH) is characterized by frequent activating mutations involving the mitogen-activated protein kinase (MAPK) pathway. Therefore, downstream markers of MAPK pathway activation such as cyclin D1 may be useful novel diagnostic neoplasia in LCH. The goal this study was to investigate expression LCH and reactive accumulations using immunohistochemistry on archival tissue. All cases tested (39/39) showed CD1a/Langerin cells. Most (22/39; 56%) strong majority (≥50%)...
The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations the are frequent genetic drivers cancer, including myelodysplastic syndromes (MDS) acute myeloid leukemia (AML). Here, using dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair replication as dependencies cohesin-mutant cells. We demonstrated increased levels sensitivity cells to poly(ADP-ribose) polymerase (PARP)...