Michaela Bowden
A5072502166- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- Estrogen and related hormone effects
- Bladder and Urothelial Cancer Treatments
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Advanced Proteomics Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- MicroRNA in disease regulation
- Immune cells in cancer
- Radiomics and Machine Learning in Medical Imaging
- Neuroendocrine Tumor Research Advances
- Protein Degradation and Inhibitors
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Advanced Breast Cancer Therapies
- Urinary and Genital Oncology Studies
- Peptidase Inhibition and Analysis
- Cancer, Stress, Anesthesia, and Immune Response
- Peroxisome Proliferator-Activated Receptors
- 3D Printing in Biomedical Research
Bristol-Myers Squibb (United States)
2019-2022
Dana-Farber Cancer Institute
2014-2020
Harvard University
2014-2020
Brigham and Women's Hospital
2015-2017
Dana-Farber Brigham Cancer Center
2017
Boston University
2016
Tufts University
2005-2008
Dublin City University
2001-2003
Clarity Centre for Sensor Web Technologies
2003
University of Auckland
1995
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of cancer and has a poor outcome. It been proposed that fallopian tube cancers may be precursors HGSOC but evolutionary evidence for this hypothesis limited. Here, we perform whole-exome sequence copy number analyses laser capture microdissected lesions (p53 signatures, tubal intraepithelial carcinomas (STICs), carcinomas), cancers, metastases from nine patients. The majority tumor-specific alterations in were present...
Immune checkpoint blockade, exemplified by antibodies targeting the PD-1 receptor, can induce durable tumor regressions in some patients. To enhance efficacy of existing immunotherapies, we screened for small molecules capable increasing activity T cells suppressed PD-1. Here, show that short-term exposure to small-molecule inhibitors cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T-cell activation, contributing antitumor effects vivo, due part derepression NFAT family...
Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse hematologic cancers. We hypothesized that checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore reactivity through a graft-versus-tumor effect.
Ex vivo systems that incorporate features of the tumor microenvironment and model dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology development effective combination therapies. Here, we demonstrate ability interrogate ex ICB using murine- patient-derived organotypic spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse human tumors retain autologous lymphoid myeloid cell populations respond short-term three-dimensional microfluidic...
Significance Alternative RNA splicing and the spliceosome machinery have been implicated in cancer progression. A genome-wide CRISPR screen identified processing factor heterogeneous nuclear ribonucleoprotein L (HNRNPL) as required for prostate growth by regulating alternative circular formation. HNRNPL its clients are overexpressed during progression, supporting their potential role therapeutic targets.
Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy.
As the field of cancer immunotherapy continues to advance at a fast pace, treatment approaches and drug development are evolving rapidly maximize patient benefit. New agents commonly evaluated for activity in patients who had previously received programmed death receptor 1 (PD-1)/programmed death-ligand (PD-L1) inhibitor as standard care or an investigational study. However, because kinetics patterns response PD-1/PD-L1 blockade, lack consistency clinical definitions resistance therapy,...
Abstract Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective patients with immune-responsive tumors. Most cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance remains a major challenge and defines the biggest unmet medical need oncology worldwide. In collaborative workshop, thought leaders from academic, biopharma, nonprofit sectors convened...
Triple-negative breast cancers (TNBCs) are a heterogeneous set of that defined by the absence hormone receptor expression and HER2 amplification. Here, we found inducible IκB kinase-related (IKK-related) kinase IKBKE JAK/STAT pathway activation compose cytokine signaling network in immune-activated subset TNBC. We treatment cultured IKBKE-driven cancer cells with CYT387, potent inhibitor TBK1/IKBKE JAK signaling, impairs proliferation, while inhibition alone does not. CYT387 inhibited both...
While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and in the microenvironment are co-dependent co-evolve. Few human studies date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected non-neoplastic prostate epithelial tissue compared it non-transformed neoplastic low-grade high-grade radical prostatectomies, each with its immediately surrounding Whereas benign prostates without...
The estrogen receptor (ER) drives the growth of most luminal breast cancers and is primary target endocrine therapy. Although ER blockade with drugs such as tamoxifen very effective, a major clinical limitation development resistance especially in setting metastatic disease. Preclinical observations suggest that even following resistance, signaling continues to exert pivotal role tumor progression majority cases. Through analysis cistrome tamoxifen-resistant cancer cells, we have uncovered...
Abstract Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive cancer, defined by the progression localized disease to metastasis, is responsible for majority of cancer–associated mortality. Recent gene expression profiling has proven successful in predicting outcome cancer patients; however, they have yet provide targeted therapy approaches that could inhibit a patient's metastatic disease. Experimental Design: We interrogated total seven...
Significance The interplay between microRNAs and the cell-cycle machinery in vivo remains poorly understood. Here we report that microRNA family miR-34/449 plays an essential rate-limiting role repressing proteins enforcing exit during epithelial cell differentiation. We demonstrate genetic ablation of entire leads to derepression cycle-promoting differentiating cells, thereby preventing their timely exit. This, turn, impairs ciliation profound developmental defects. Hence, this study...
KRAS mutation is present in approximately 30% of human lung adenocarcinomas. Although recent advances targeted therapy have shown great promise, effective targeting remains elusive, and concurrent alterations tumor suppressors render KRAS-mutant tumors even more resistant to existing therapies. Contributing the refractoriness are immunosuppressive mechanisms, such as increased presence suppressive regulatory T cells (Treg) elevated expression inhibitory receptor PD-1 on tumor-infiltrating...
Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond checkpoint inhibitors remain largely unexplored. We assessed marker expression, lymphocytic infiltrate, associated mutational profiles in a cohort of small intestine pancreatic NETs. Methods expression PDCD1 (PD-1), CD274 (PD-L1), PDCD1LG2 (PD-L2) archival tissue from 64 (SINETs) 31 NETs (pNET). additionally T-cell infiltrates, categorizing subsets based on markers CD3, CD8, CD45RO (PTPRC), or...
Intra-tumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype–phenotype we developed methods for targeted mutation detection in DNA RNA isolated from thousands single cells five CLL samples. By clearly resolving phylogenic uncovered mutated LCP1 WNK1 as novel drivers, supported functional evidence...
Transcriptome deconvolution in cancer and other heterogeneous tissues remains challenging. Available methods lack the ability to estimate both component-specific proportions expression profiles for individual samples. We present DeMixT, a new tool deconvolve high-dimensional data from mixtures of more than two components. DeMixT implements an iterated conditional mode algorithm novel gene-set-based component merging approach improve accuracy. In series experimental validation studies...
Abstract High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non–muscle-invasive with unpredictable outcome and poorly understood factors. Here, we examined association somatic mutation profiles nonrecurrent disease (GO, good outcome), recurrence (R), or progression (PD) in a cohort HGT1 patients. Exome sequencing was performed on 62 15 matched normal tissue samples. Both tumor only (TO) paired analyses were performed, focusing 95 genes known to be mutated cancer. Somatic...