A5025185025- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Gene expression and cancer classification
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- Genomics and Phylogenetic Studies
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Gene Regulatory Network Analysis
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Pancreatic and Hepatic Oncology Research
- Immunotherapy and Immune Responses
- Evolution and Genetic Dynamics
- Pluripotent Stem Cells Research
- Genetics, Bioinformatics, and Biomedical Research
- Genetic factors in colorectal cancer
Memorial Sloan Kettering Cancer Center
2013-2023
Bioinformatics Institute
2023
Swim Across America
2016-2021
Kettering University
2015-2020
Stanford University
2009-2017
Icahn School of Medicine at Mount Sinai
2017
New York Proton Center
2015
National Institutes of Health
2014-2015
University of Michigan–Ann Arbor
2009-2014
Washtenaw Community College
2012-2013
Chris Sander and colleagues have extracted significant functional events from 12 tumor types. Tumors can be classified as being driven largely by either mutation or copy number changes, and, within this division, subclasses of cross-tissue patterns are discerned that suggest sets combinatorial therapies. Cancer therapy is challenged the diversity molecular implementations oncogenic processes resulting variation in therapeutic responses. Projects such The Genome Atlas (TCGA) provide maps...
Tumor-infiltrating immune cells have been linked to prognosis and response immunotherapy; however, the levels of distinct cell subsets signals that draw them into a tumor, such as expression antigen presenting machinery genes, remain poorly characterized. Here, we employ gene expression-based computational method profile infiltration 24 populations in 19 cancer types. We compare types using an score T find clear renal carcinoma (ccRCC) is among highest for both scores. Using profiles well...
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress immuno-oncology will require detailed understanding infiltrative landscape found these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA)...
Abstract With only a fraction of patients responding to cancer immunotherapy, better understanding the entire tumor microenvironment is needed. Using single-cell transcriptomics, we chart fibroblastic landscape during pancreatic ductal adenocarcinoma (PDAC) progression in animal models. We identify population carcinoma-associated fibroblasts (CAF) that are programmed by TGFβ and express leucine-rich repeat containing 15 (LRRC15) protein. These LRRC15+ CAFs surround islets absent from normal...
Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially the bladder, breast, kidney, to be depleted mtDNA, relative matched normal tissue. Analysis genetic context reveals an association between incidence several somatic alterations, including IDH1 mutations gliomas, content. In but not...
On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation copy number, RNA, protein expression), we classified 894 renal cell carcinomas (RCCs) various histologic types into nine major genomic subtypes. Site origin within nephron was one determinant in classification, reflecting differences among clear cell, chromophobe, papillary RCC. Widespread changes associated with TFE3 gene fusion or chromatin modifier genes were present a specific...
Consensus clustering (CC) has been adopted for unsupervised class discovery in many genomic studies. It calculates how frequently two samples are grouped together repeated runs and uses the resulting pairwise "consensus rates" visual demonstration that clusters exist, comparing cluster stability estimating optimal number (K). However, sensitivity specificity of CC have not systemically assessed. Through simulations we find is able to divide randomly generated unimodal data into apparently...
// Luc G.T. Morris 1,2,* , Nadeem Riaz 1,3* Alexis Desrichard 1 Yasin Şenbabaoğlu 4 A. Ari Hakimi 2 Vladimir Makarov Jorge S. Reis-Filho 1,5 and Timothy Chan 1,3 Human Oncology Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA Department of Surgery, 3 Radiation Oncology, Computational Biology 5 Pathology, * These authors have contributed equally to this work Correspondence to: Morris, email: Chan, Keywords : heterogeneity, evolution, survival, cancer, immune...
Although immune checkpoint inhibitors (ICIs) are established as effective cancer therapies, overcoming therapeutic resistance remains a critical challenge. Here we identify interleukin 6 (IL-6) correlate of poor response to atezolizumab (anti-PD-L1) in large clinical trials advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade PD-L1 the IL-6 receptor (IL6R) causes synergistic regression tumors substantially improves anti-tumor CD8+ cytotoxic T lymphocyte...
Abstract Cellular interactions can be modeled as complex dynamical systems represented by weighted graphs. The functionality of such networks, including measures robustness, reliability, performance and efficiency, are intrinsically tied to the topology geometry underlying graph. Utilizing recently proposed geometric notions curvature on graphs, we investigate features gene co-expression networks derived from large-scale genomic studies cancer. We find that these reliably distinguishes...
Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal well tumor development. However, the of signaling breast cancer cells (CSC) remains to be determined. We utilized lentiviral reporter system identify subset with higher activity (Notch(+)) or reduced (Notch(-)) multiple lines. Using vitro and mouse xenotransplantation assays, we investigated pathway CSC regulation. Breast increased displayed sphere formation expression markers. Interestingly...
Microsatellite-stable colorectal cancer (MSS-CRC) is highly refractory to immunotherapy. Understanding tumor-intrinsic determinants of immunotherapy resistance critical improve MSS-CRC patient outcomes. Here, we demonstrate that high tumor expression the core autophagy gene ATG16L1 associated with poor clinical response anti-PD-L1 therapy in KRAS-mutant tumors from IMblaze370 (NCT02788279), a large phase III trial atezolizumab (anti-PD-L1) advanced metastatic MSS-CRC. Deletion Atg16l1...
Abstract Context Most papillary microcarcinomas (PMCs) are indolent and subclinical. However, as many 10% can present with clinically significant nodal metastases. Objective Design Characterization of the genomic transcriptomic landscape PMCs presenting or without important lymph node Subjects Samples Formalin-fixed paraffin-embedded PMC samples from 40 patients lateral neck metastases (pN1b) 71 documented absence disease (pN0). Outcome Measures To interrogate DNA alterations in 410 genes...
Protein expression and post-translational modification levels are tightly regulated in neoplastic cells to maintain cellular processes known as 'cancer hallmarks'. The first Pan-Cancer initiative of Cancer Genome Atlas (TCGA) Research Network has aggregated protein profiles for 3,467 patient samples from 11 tumor types using the antibody based reverse phase array (RPPA) technology. resultant proteomic data can be utilized computationally infer protein-protein interaction (PPI) networks study...
Accurate classification of glioblastoma multiforme (GBM) is crucial for understanding its biologic diversity and informing diagnosis treatment. The Cancer Genome Atlas (TCGA) project identified four GBM classes using gene expression data separately three methylation data. We sought to integrate multiple types in classification, understand features the newly defined subtypes, reconcile with prior studies.We used allele-specific copy number estimate aneuploid content each tumor incorporated...
BackgroundPancreatic adenocarcinoma (PDAC) is a lethal cancer with <7% of patients surviving past 5 years.T cell immunity has been linked to the exceptional outcome rare long-term survivors but antigens are unknown.Methods To identify T in PDAC survivors, we assembled largest cohorts stage-matched short [n=68, median overall survival (OS) 0.8y] and (n=82, OS 6y).To enable antigen discovery, performed combined analysis whole exome sequencing, neoantigen prediction, receptor (TCR) Vβ-chain...