A5062304915- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Pericarditis and Cardiac Tamponade
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cardiac tumors and thrombi
- Cancer Research and Treatments
- Myasthenia Gravis and Thymoma
- Phagocytosis and Immune Regulation
- Cancer, Lipids, and Metabolism
- Immunotherapy and Immune Responses
- Atherosclerosis and Cardiovascular Diseases
- Lymphatic System and Diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Ovarian cancer diagnosis and treatment
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Cardiac Imaging and Diagnostics
- Kawasaki Disease and Coronary Complications
- Cardiovascular Function and Risk Factors
- Dietary Effects on Health
Massachusetts General Hospital
2019-2025
Harvard University
2019-2025
Harvard–MIT Division of Health Sciences and Technology
2019-2024
Massachusetts Institute of Technology
2019-2024
Cleveland Clinic
2022-2024
Georgetown University
2023-2024
Broad Institute
2024
Vanderbilt University Medical Center
2024
Stanford University
2024
Apollo Hospitals
2024
Significance Despite initial responsiveness to chemotherapy, the overwhelming majority of advanced ovarian cancer patients relapse with resistant disease. Thus, developing more effective strategies for treatment is a high clinical priority. Here, we report that targeting angiotensin signaling losartan, an receptor blocker, can reduce extracellular matrix in tumors and associated physical barriers normally hinder drug delivery efficacy. These changes tumor microenvironment lead improved...
Abstract The mechanisms behind the antitumor effects of exercise training (ExTr) are not fully understood. Using mouse models established breast cancer, we examined here causal role CD8+ T cells in benefit acquired from ExTr tumor control, as well ability to improve immunotherapy responses. We implanted E0771, EMT6, MMTV-PyMT, and MCa-M3C cancer orthotopically wild-type or Cxcr3−/− female mice initiated intensity-controlled sessions when tumors reached approximately 100 mm3. characterized...
Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models orthotopic pMMR CRC liver accurately recapitulate the inefficacy ICB therapy in patients, whereas same tumors sensitive when grown subcutaneously. To reveal local, nonmalignant components determine sensitivity treatment, compared...
Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, CD8 + T cell blocking studies mice, demonstrated this results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment disrupts the blood–tumor barrier. Used lieu of immunosuppressive corticosteroids, angiotensin receptor blocker...
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen–specific T cell generation and effective anticancer immune responses. However, TDLNs often the primary site of metastasis, causing suppression worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer heterogeneity, plasticity, evasion during breast progression node metastasis (LNM). A subset cells in exhibited elevated MHC class II (MHC-II) gene expression both mice humans....
Adding losartan (LOS) to FOLFIRINOX (FFX) chemotherapy followed by chemoradiation (CRT) resulted in 61% R0 surgical resection our phase II trial patients with locally advanced pancreatic cancer (LAPC). Here we identify potential mechanisms of benefit assessing the effects neoadjuvant LOS on tumor microenvironment.
Host-directed therapies (HDTs) represent an emerging approach for bacterial clearance during tuberculosis (TB) infection. While most HDTs are designed and implemented immuno-modulation, other host targets-such as nonimmune stromal components found in pulmonary granulomas-may prove equally viable. Building on our previous work characterizing normalizing the aberrant granuloma-associated vasculature, here we demonstrate that FDA-approved (bevacizumab losartan, respectively) can be repurposed...
Biclustering is a very popular method to identify hidden co-regulation patterns among genes. There are numerous biclustering algorithms designed undertake this challenging task, however, thorough comparison between these even harder accomplish due lack of ground truth and large variety in the search strategies objectives algorithms. In paper, we address less studied, yet important problem formally analyze several terms bicluster they attempt discover. We systematically formulate requirements...
A single dose of bevacizumab reduced the density angiopoietin-2-positive vessels while improving infiltration CD4+ T and CD8+ cells, mature dendritic cells in patients with primary triple-negative breast cancer. Our findings provide a rationale for including during neoadjuvant treatment to enhance efficacy immune checkpoint blockers this disease.
MDC1A, the second most prevalent form of congenital muscular dystrophy, results from laminin-α2 chain deficiency. This disease is characterized by extensive muscle wasting that in extremely weak skeletal muscles. A large percentage children with MDC1A are faced respiratory as well ambulatory difficulties. We investigated effects overexpressing insulin-like growth factor-1 (IGF-1) a potential therapeutic target for Lama2Dy-w mouse, model closely resembles human MDC1A. IGF-1 transgenic mice...
Medical images are acquired at high resolutions with large fields of view in order to capture fine-grained features necessary for clinical decision-making. Consequently, training deep learning models on medical can incur computational costs. In this work, we address the challenge downsizing improve downstream efficiency while preserving clinically-relevant features. We introduce MedVAE, a family six large-scale 2D and 3D autoencoders capable encoding as downsized latent representations...
Abstract: Person re-identification (ReID) is a critical task in surveillance, security, and access control systems, aiming to consistently recognize individuals across time varying environments. While deep learning face-based methods dominate recent advancements, they often face limitations related computational complexity, dependence on highquality data, vulnerability occlusions, lighting variations, appearance changes. This literature survey critically evaluates key ReID methodologies,...
Introduction Exercise is recommended as an adjunct therapy in cancer, but its effectiveness varies. Our hypothesis that the benefit depends on exercise intensity. Methods We subjected mice to low intensity (Li), moderate (Mi) or high (Hi) exercise, untrained control (Co) groups based their individual maximal running capacity. Results found played a critical role tumor control. Only Mi delayed growth and reduced burden, whereas Li Hi failed exert similar antitumor effects. While both...
Abstract Group 3 Medulloblastoma (G3MB) is a pediatric brain cancer with poor prognosis, and median 5-year overall survival of 45-58% in infants young children, respectively. Moreover, the current standard-of-care therapy – which includes spinal radiation causes tremendous morbidity. While immunotherapy immune checkpoint blockade has transformed treatment many malignancies, it yet to show benefit most common form tumors. Here we that B cell depletion using Rituximab; anti-CD20: -- an...
Introduction: Red cell distribution width (RDW), expressed in femtoliters (), is a measure of the variation size circulating erythrocytes. Due to its close relation inammation RDW can be used as tool for early diagnosis, an inammatory marker, and mortality indicator case hypertension which chronic state. In this study we aim observe mean value red (RDW) hypertensive, pre hypertensive normotensive patients. Methodology: A cross sectional was conducted over period 18 months outpatient wards...
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is an autosomal recessive disorder caused by mutations in the laminin-α2 gene (OMIM: 607855). Currently, no treatment other than palliative care exists for this disease. In our previous work, genetic interventions Lama2Dy-w mouse model MDC1A demonstrated that limited regeneration and uncontrolled apoptosis are important drivers of However, targeting one these disease without addressing results only partial rescue phenotype. The...
Abstract Our recent studies uncovered a novel GABA signaling pathway in embryonic forebrain endothelial cells that works independently from neuronal and revealed disruptions A receptor-GABA early stages can directly contribute to the origin of psychiatric disorders. In receptor β3 subunit cell conditional knockout ( Gabrb3 ECKO ) mice, is deleted selectively cells, therefore receptors become inactivated dysfunctional. There reduction vessel densities increased morphology telencephalon...
Abstract Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis support immune surveillance. Damage LMCs disrupts function is related various diseases. Despite their importance, knowledge transcriptional signatures in how they relate normal disease contexts largely missing. We have generated a comprehensive single-cell atlas—including LMCs—of mouse...
Prenatal NAD + treatment can rescue abnormal brain development and prevent the origin of mental illness.