Massachusetts Institute of Technology

The Broad Institute, Inc.

The Brigham and Women's Hospital, Inc.

Dana-farber-cancer Institute Inc.

The General Hospital Corporation

University of California

Harvard College

Orit Rozenblatt-Rosen

Aviv Regev

Ana Carrizosa Anderson

Asaf Rotem

Benjamin Izar

Vijay K Kuchroo

Alexander K Shalek

Jellert Gaublomme

Moshe Biton

Adam Haber

Ayshwarya Subramanian

Livnat Jerby

David A Weitz

Eric Lander

Le Cong

Levi A Garraway

Ramnik Xavier

Jonathan S Weissman

Thomas W Norman

Meromit Singer

Anindita Basu

Karthik Shekhar

Brian Cleary

Rebecca H Herbst

Atray Dixit

Itay Tirosh

Jose Ordovas-Montanes

Christopher Smillie

Nir Hacohen

Naomi Habib

Oren Parnas

Jayaraj Rajagopal

Daniel Montoro

Bo Li

Karin Pelka

Matan Hofree

Elizabeth Stover

Noga Rogel

Kathryn Geiger-Schuller

Brittany Adamson

Jonathan Chen

Eugene Drokhlyansky

Pratiksha Thakore

Davide Mangani

Linglin Huang

Inbal Avraham-Davidi

The present invention is generally directed to a colorectal (CRC) cell atlas that provides methods of predicting outcomes of cancer patients and therapeutic targets for treating patients in need thereof. The atlas may be used to predict a response to immunotherapy, in particular checkpoint blockade therapy and adoptive cell transfer. Disclosed herein are previously unidentified gene programs in tumors that can be used to predict response and provide for therapeutic targets that can be used to shift a tumor to a responsive phenotype.

Methods for predicting outcomes and treating colorectal cancer using a cell atlas

Provided herein are methods and compositions for identifying ionocytes from respiratory epithelial cells, and uses of such cells for treatment of inflammatory lung disease. Also provided herein are methods and compositions for modulating respiratory tract epithelial cell proliferation, differentiation, maintenance, and/or function.

Respiratory and sweat gland ionocytes

An atlas of intestinal epithelial cells, intestinal epithelial stem cells and intestinal immune cells identifies new cell populations, markers, networks, and responses to stimuli. Intestinal T cells drive intestinal epithelial cell differentiation and activity. Accordingly, disclosed are methods of modulating intestinal epithelial cell differentiation, maintenance and/or function, related methods for the treatment of disease, including IBD. Also disclosed are methods and kits for identifying cell types, their differentiation, homeostasis and activation.

Modulation of intestinal epithelial cell differentiation, maintenance and/or function through T cell action

Techniques Nuc-seq, Div-Seq, and Dronc-Seq are allow for unbiased analysis of any complex tissue. Nuc-Seq, a scalable single nucleus RNA-Seq method, can sensitively identify closely related cell types, including within the adult hippocampus. Div-seq combines Nuc-Seq with EdU-mediated labeling of proliferating cells, allowing tracking of transcriptional dynamics of newborn neurons in an adult neurogenic region in the hippocampus. Dronc-Seq uses a microfluidic device to co-encapsulate individual nuclei in reverse emulsion aqueous droplets in an oil medium together with one uniquely barcoded mRNA-capture bead.

Methods for determining spatial and temporal gene expression dynamics during adult neurogenesis in single cells

The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically. Specifically, disclosed is a resistance program identified by a comprehensive single-cell profiling study in melanoma patients, which was validated in two large validation cohorts. Using a large-scale in silico prediction, CDK4/6 inhibitors were identified as a class of drugs that may reverse this resistance program. These predictions were validated in melanoma cell lines, patient-derived co-culture models, and melanoma in vivo models, which show that the combination of abemaciclib and immune checkpoint blockade (ICB) overcome intrinsic drug resistance. The present invention provides for detecting an immunotherapy resistance signature and modulating the signature with CDK4/6 inhibition. Also provided is a novel phased immunotherapy and CDK4/6 inhibitor combination therapy regimen.

Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer

This invention relates generally to compositions and methods for modulating complement component 3 (C3) activity or expression to treat, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells.

Compositions and methods targeting complement component 3 for inhibiting tumor growth

The present invention is generally directed to identify interacting cells in the tumor microenvironment and using the identified interactions to enhance anti-tumor immunity in cancer. Identified interactions can be modulated using therapeutic agents. Immune cells resistant to suppression can be used for adoptive cell transfer. The present invention is also generally directed to cell types and genes that are correlated to time of tumor growth and tumor size.

Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment

Described herein are compositions and methods of using single-cell RNA-sequencing to identify treatment resistance in patients with ovarian cancer. Also, described herein are compositions and methods for treatment targeting resistance in patients with ovarian cancer.

Compositions and methods for treating ovarian tumors

The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically.

The present invention provides methods and tools for analyzing genetic interactions. The subject matter disclosed herein is generally directed to single cell genomics and proteomics. In one embodiment provided is a method of cell and nuclei hashing using sample barcodes. In another embodiment are method of performing genomewide CRISPR perturbation screens.

Methods and compositions for multiplexing single cell and single nuclei sequencing

The present invention provides tools and methods for the systematic analysis of genetic interactions, including higher order interactions. The present invention provides tools and methods for combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.

Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction

Growing community of inventors

Cambridge, MA, United States of America

Orit Rozenblatt-Rosen