947 results match your criteria: "Weill Cornell Graduate School[Affiliation]"
Cell Stem Cell
May 2023
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Center for Genomic Health, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address:
Human pluripotent stem cells (hPSCs) and three-dimensional organoids have ushered in a new era for disease modeling and drug discovery. Over the past decade, significant progress has been in deriving functional organoids from hPSCs, which have been applied to recapitulate disease phenotypes. In addition, these advancements have extended the application of hPSCs and organoids for drug screening and clinical-trial safety evaluations.
View Article and Find Full Text PDFElife
May 2023
Immunology Program, Sloan Kettering Institute, New York, United States.
Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2.
View Article and Find Full Text PDFMagnetic resonance (MR) relaxometry is a quantitative imaging method that measures tissue relaxation properties. This review discusses the state of the art of clinical proton MR relaxometry for glial brain tumors. Current MR relaxometry technology also includes MR fingerprinting and synthetic MRI, which solve the inefficiencies and challenges of earlier techniques.
View Article and Find Full Text PDFNeuroradiol J
April 2023
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Aim: Because the tongue is a midline structure, studies on the neural correlates of lateralized tongue function are challenging and remain limited. Patients with tongue cancer who undergo unilateral partial glossectomy may be a unique cohort to study tongue-associated cortical activation, particularly regarding brain hemispheric lateralization. This longitudinal functional magnetic resonance imaging (fMRI) study investigated cortical activation changes for three tongue tasks before and after left-sided partial glossectomy in patients with squamous cell carcinoma of the tongue.
View Article and Find Full Text PDFCurr Opin Immunol
August 2023
The Jill Roberts Institute for Research in Inflammatory Bowel Disease, New York, NY, USA; Joan and Sanford I. Weill Department of Medicine, New York, NY, USA; Department of Microbiology and Immunology, New York, NY, USA; Sandra and Edward Meyer Cancer Center, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA. Electronic address:
Viral blockade of the transporter associated with antigen processing (TAP) diminishes surface and endosomal recycling compartment levels of major histocompatibility complex class-I (MHC-I) in dendritic cells (DCs), and compromises both classical MHC-I presentation and canonical cross-presentation during infection to impair CD8 T-cell immunity. Virus-specific CD8 T cells are thought to be cross-primed mostly by uninfected TAP-sufficient DCs through cross-presentation of viral peptides from internalized virus-infected dying cells. The dilemma is that CD8 T cells primed to TAP-dependent viral peptides are mismatched to the TAP-independent epitopes presented on tissues infected with immune-evasive viruses.
View Article and Find Full Text PDFNat Commun
April 2023
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tissue homeostasis is maintained after stress by engaging and activating the hematopoietic stem and progenitor compartments in the blood. Hematopoietic stem cells (HSCs) are essential for long-term repopulation after secondary transplantation. Here, using a conditional knockout mouse model, we revealed that the RNA-binding protein SYNCRIP is required for maintenance of blood homeostasis especially after regenerative stress due to defects in HSCs and progenitors.
View Article and Find Full Text PDFEur Radiol
September 2023
Department of Radiology, Neuroradiology Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Objectives: Language reorganization may follow tumor invasion of the dominant hemisphere. Tumor location, grade, and genetics influence the communication between eloquent areas and tumor growth dynamics, which are drivers of language plasticity. We evaluated tumor-induced language reorganization studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness).
View Article and Find Full Text PDFBrain Commun
March 2023
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA.
bioRxiv
March 2023
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Two distinct fates, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common progenitor cells, the inner cell mass (ICM), in mammalian embryos. To study how these sister identities are forged, we leveraged embryonic (ES) and etraembryonic doderm (XEN) stem cells - counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses uncovered distinct rates, efficiencies and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions.
View Article and Find Full Text PDFJ Neuroimaging
July 2023
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Background And Purpose: Resting-state functional magnetic resonance imaging (rsfMRI) has been proposed as an alternative to task-based fMRI including clinical situations such as preoperative brain tumor planning, due to advantages including ease of performance and time savings. However, one of its drawbacks is the limited ability to accurately lateralize language function.
Methods: Using the rsfMRI data of healthy controls, we carried out a power spectra analysis on three regions of interest (ROIs): Broca's area (BA) in the frontal cortex for language, hand motor (HM) area in the primary motor cortex, and the primary visual cortex (V1).
Sci Adv
April 2023
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
The mechanisms underlying -driven prostate cancer initiation and progression remain poorly understood due to a lack of model systems that recapitulate this phenotype. We generated a genetically engineered mouse with prostate-specific expression of the factor, ETV4, at lower and higher protein dosage through mutation of its degron. Lower-level expression of ETV4 caused mild luminal cell expansion without histologic abnormalities, and higher-level expression of stabilized ETV4 caused prostatic intraepithelial neoplasia (mPIN) with 100% penetrance within 1 week.
View Article and Find Full Text PDFNat Biotechnol
January 2024
Center for Bioinformatics and Computational Biology, Houston Methodist Research Institute, Houston, TX, USA.
RNA velocity provides an approach for inferring cellular state transitions from single-cell RNA sequencing (scRNA-seq) data. Conventional RNA velocity models infer universal kinetics from all cells in an scRNA-seq experiment, resulting in unpredictable performance in experiments with multi-stage and/or multi-lineage transition of cell states where the assumption of the same kinetic rates for all cells no longer holds. Here we present cellDancer, a scalable deep neural network that locally infers velocity for each cell from its neighbors and then relays a series of local velocities to provide single-cell resolution inference of velocity kinetics.
View Article and Find Full Text PDFSemin Immunol
May 2023
Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA; The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA. Electronic address:
The dynamic and complex community of microbes that colonizes the intestines is composed of bacteria, fungi, and viruses. At the mucosal surfaces, immunoglobulins play a key role in protection against bacterial and fungal pathogens, and their toxins. Secretory immunoglobulin A (sIgA) is the most abundantly produced antibody at the mucosal surfaces, while Immunoglobulin G (IgG) isotypes play a critical role in systemic protection.
View Article and Find Full Text PDFRes Sq
March 2023
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here we analyzed transcription in species across the tree of life.
View Article and Find Full Text PDFSTAR Protoc
March 2023
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Biomedical Sciences, Cornell University, New York, NY 10065, USA. Electronic address:
Here, we focus on tumor-associated macrophages (TAMs) in the PyMT model of breast cancer, detailing a protocol for assessing antigen presentation capabilities of immune populations of interest. We describe a stringent bone marrow chimera system to demonstrate presentation of exogenous antigen that is acquired and processed in the tumor microenvironment. We describe steps for testing antigen presentation activity of TAMs to CD8 T cells in vivo and ex vivo and the requirement for the transcription factor IRF8 in this function.
View Article and Find Full Text PDFJ Immunother Cancer
March 2023
National Cancer Institute, Bethesda, Maryland, USA
Immunotherapy is the standard of care for several cancers and the field continues to advance at a rapid pace, with novel combinations leading to indications in an increasing number of disease settings. Durable responses and long-term survival with immunotherapy have been demonstrated in some patients, though lack of initial benefit and recurrence after extended disease control remain major hurdles for the field. Many new combination regimens are in development for patients whose disease progressed on initial immunotherapy.
View Article and Find Full Text PDFJ Bacteriol
April 2023
Immunology Program, Sloan Kettering Institute, New York, New York, USA.
RNase H enzymes participate in various processes that require processing of RNA-DNA hybrids, including DNA replication, transcription, and ribonucleotide excision from DNA. Mycobacteria encode multiple RNase H enzymes, and prior data indicate that RNase HI activity is essential for mycobacterial viability. However, the additional roles of mycobacterial RNase Hs are unknown, including whether RNase HII (RnhB and RnhD) excises chromosomal ribonucleotides misincorporated during DNA replication and whether individual RNase HI enzymes (RnhA and RnhC) mediate additional phenotypes.
View Article and Find Full Text PDFNat Mater
March 2023
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Medulloblastoma is the most common malignant paediatric brain tumour, with ~30% mediated by Sonic hedgehog signalling. Vismodegib-mediated inhibition of the Sonic hedgehog effector Smoothened inhibits tumour growth but causes growth plate fusion at effective doses. Here, we report a nanotherapeutic approach targeting endothelial tumour vasculature to enhance blood-brain barrier crossing.
View Article and Find Full Text PDFSTAR Protoc
March 2023
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School of Biomedical Sciences, Cornell University, New York, NY 10065, USA. Electronic address:
Group 1 innate lymphocytes are heterogeneous, and their ontogeny and function remain ambiguous. Here, we describe a protocol to measure cell ontogeny and effector functions of natural killer (NK) and ILC1 subsets based on current understanding of their differentiation pathways. We use cre drivers to genetically fate-map cells, tracking plasticity between mature NK and ILC1.
View Article and Find Full Text PDFDevelopment
March 2023
Biochemistry, Cell & Developmental Biology, and Molecular Biology (BCMB) program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Proper muscle contraction requires the assembly and maintenance of sarcomeres and myofibrils. Although the protein components of myofibrils are generally known, less is known about the mechanisms by which they individually function and together synergize for myofibril assembly and maintenance. For example, it is unclear how the disruption of actin filament (F-actin) regulatory proteins leads to the muscle weakness observed in myopathies.
View Article and Find Full Text PDFChannels (Austin)
December 2023
Neuroscience Program, Weill Cornell Graduate School of Medical Sciences, New York, USA.
Recent human genetic studies have linked a variety of genetic variants in the and genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Ca1.2 and Ca1.
View Article and Find Full Text PDFImmunity
February 2023
Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:
Regulatory T (Treg) cells represent a distinct lineage of cells of the adaptive immune system indispensable for forestalling fatal autoimmune and inflammatory pathologies. The role of Treg cells as principal guardians of the immune system can be attributed to their ability to restrain all currently recognized major types of inflammatory responses through modulating the activity of a wide range of cells of the innate and adaptive immune system. This broad purview over immunity and inflammation is afforded by the multiple modes of action Treg cells exert upon their diverse molecular and cellular targets.
View Article and Find Full Text PDFElife
February 2023
Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, United States.
M-CSF is a critical growth factor for myeloid lineage cells, including monocytes, macrophages, and osteoclasts. Tissue-resident macrophages in most organs rely on local M-CSF. However, it is unclear what specific cells in the bone marrow produce M-CSF to maintain myeloid homeostasis.
View Article and Find Full Text PDFJ Gen Physiol
April 2023
Department of Physiology and Biophysics, Weill Cornell Medicine , New York, NY, USA.
A perennial problem encountered when using small molecules (drugs) to manipulate cell or protein function is to assess whether observed changes in function result from specific interactions with a desired target or from less specific off-target mechanisms. This is important in laboratory research as well as in drug development, where the goal is to identify molecules that are unlikely to be successful therapeutics early in the process, thereby avoiding costly mistakes. We pursued this challenge from the perspective that many bioactive molecules (drugs) are amphiphiles that alter lipid bilayer elastic properties, which may cause indiscriminate changes in membrane protein (and cell) function and, in turn, cytotoxicity.
View Article and Find Full Text PDFBlood
June 2023
Center for Cell Engineering and Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY.
Cell therapies that rely on engineered immune cells can be enhanced by achieving uniform and controlled transgene expression in order to maximize T-cell function and achieve predictable patient responses. Although they are effective, current genetic engineering strategies that use γ-retroviral, lentiviral, and transposon-based vectors to integrate transgenes, unavoidably produce variegated transgene expression in addition to posing a risk of insertional mutagenesis. In the setting of chimeric antigen receptor (CAR) therapy, inconsistent and random CAR expression may result in tonic signaling, T-cell exhaustion, and variable T-cell persistence.
View Article and Find Full Text PDF