Patents by Inventor Alexander K. Shalek

Alexander K. Shalek has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20240156816
    Abstract: Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.
    Type: Application
    Filed: December 15, 2023
    Publication date: May 16, 2024
    Inventors: Alexander K. Shalek, Peter Winter, David Weinstock, Mark Murakami, Scott Manalis, Andrew Navia, Jennyfer Galvez-Reyes
  • Publication number: 20240150453
    Abstract: The subject matter disclosed herein is generally directed to stratifying and treating inflammatory diseases. In particular, the present invention provides for detecting treatment naive cell states that predict the response of a subject having inflammatory bowel disease to anti-TNF-blockade. The cells are T cells, NK cells, innate lymphoid cells, myeloid and/or epithelial cell subsets defined by their gene expression as determined by single cell RNA sequencing. Alternatively, the responders are identified by gene expression in a sample.
    Type: Application
    Filed: March 9, 2022
    Publication date: May 9, 2024
    Inventors: Alexander K. Shalek, Leslie Kean, Jose Ordovas-Montanes, Hengqi Zheng, Benjamin Doran, Kyle Kimler
  • Publication number: 20240132976
    Abstract: The subject matter disclosed herein is generally directed to stratifying and treating coronavirus infections based on intrinsic immune states.
    Type: Application
    Filed: February 18, 2022
    Publication date: April 25, 2024
    Inventors: Alexander K. Shalek, Jose Ordovas-Montanes, Carly Ziegler, Sarah Glover, Bruce Horwitz, Vincent Miao, Anna Owings, Andrew Navia, Ying Tang, Joshua Bromley
  • Publication number: 20240068057
    Abstract: Embodiments disclosed herein provide a pan-tissue cell atlas of healthy and diseased subjects obtained by single cell sequencing. The present invention discloses novel markers for cell types. Moreover, genes associated with disease, including HIV infection and tuberculosis are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for controlling immune regulations and cell-cell communication of the cell types disclosed herein. In addition, novel cell types and methods of quantitating, detecting and isolating the cell types are disclosed.
    Type: Application
    Filed: August 21, 2023
    Publication date: February 29, 2024
    Inventors: Alexander K. Shalek, Carly Ziegler
  • Patent number: 11865168
    Abstract: Provided herein are compositions and methods for therapeutic and/or prophylactic treatment of an intracellular bacterial infection in a subject in need thereof, comprising one or more modulating agents, wherein the one or more modulating agents increase expression of IFN?, IL-2, TNF, and/or IL-17 in systemic and/or lung T cells. In some embodiments, the increase of expression of IFN?, IL-2, TNF, and/or IL-17 occurs in lung T cells. The lung T cells can be lung resident T cells or systemic T cells that are recruited to the lung. In some embodiments, the T cells are CD4+ and/or CD8+ T cells. In some embodiments, the intracellular bacterial infection is a Mycobacterium tuberculosis (MTB) infection.
    Type: Grant
    Filed: December 30, 2020
    Date of Patent: January 9, 2024
    Assignees: Massachusetts Institute of Technology, The United States of America, as represented by The Secretary, Department of Health & Human Services, University of Pittsburgh—Of The Commonwealth System of Higher Education
    Inventors: Alexander K. Shalek, Travis Hughes, Marc H. Wadsworth, Robert Seder, Mario Roederer, Joanne L. Flynn, Patricia Darrah
  • Patent number: 11844800
    Abstract: Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.
    Type: Grant
    Filed: October 30, 2020
    Date of Patent: December 19, 2023
    Assignees: Massachusetts Institute of Technology, Dana-Farber Cancer Institute, Inc.
    Inventors: Alexander K. Shalek, Peter Winter, David Weinstock, Mark Murakami, Scott Manalis, Andrew Navia, Jennyfer Galvez-Reyes
  • Publication number: 20230398130
    Abstract: The subject matter disclosed herein is generally directed to modulation of genes and pathways that drive differentiation of LGR5+ stem cells. The methods and compositions can be used to treat diseases associated with aberrant epithelial barrier function. Using novel screening methods Applicants have identified compounds that increase Paneth cell differentiation. The compounds can be used to treat diseases associated with stem cell differentiation.
    Type: Application
    Filed: October 25, 2021
    Publication date: December 14, 2023
    Inventors: Benjamin Mead, Alexander K. Shalek, Jeffrey Karp, Kazuki Hattori
  • Publication number: 20230348899
    Abstract: The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.
    Type: Application
    Filed: June 13, 2023
    Publication date: November 2, 2023
    Inventors: Peter van Galen, Volker Hovestadt, Travis Hughes, Marc H. Wadsworth II, Bradley Bernstein, Alexander K. Shalek, Todd M. Gierahn, J. Christopher Love, Ang A. Tu
  • Patent number: 11781193
    Abstract: Embodiments disclosed herein provide a pan-tissue cell atlas of healthy and diseased subjects obtained by single cell sequencing. The present invention discloses novel markers for cell types. Moreover, genes associated with disease, including HIV infection and tuberculosis are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for controlling immune regulations and cell-cell communication of the cell types disclosed herein. In addition, novel cell types and methods of quantitating, detecting and isolating the cell types are disclosed.
    Type: Grant
    Filed: October 16, 2018
    Date of Patent: October 10, 2023
    Assignee: Massachusetts Institute of Technology
    Inventors: Alexander K. Shalek, Carly Ziegler
  • Patent number: 11767557
    Abstract: Modifications to both hardware and enzymatic reactions used in single cell analyses such as but not limited to Seq-well that enable significant increases in the yield of transcripts per cell, portability and ease of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays are disclosed.
    Type: Grant
    Filed: December 7, 2018
    Date of Patent: September 26, 2023
    Assignee: Massachusetts Institute of Technology
    Inventors: J. Christopher Love, Todd Michael Gierahn, Alexander K. Shalek, Marc Havens Wadsworth, Travis K. Hughes
  • Patent number: 11732257
    Abstract: The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.
    Type: Grant
    Filed: October 23, 2018
    Date of Patent: August 22, 2023
    Assignees: Massachusetts Institute of Technology, The General Hospital Corporation
    Inventors: Peter van Galen, Volker Hovestadt, Travis Hughes, Marc H. Wadsworth, II, Bradley Bernstein, Alexander K. Shalek, Todd M. Gierahn, J. Christopher Love, Ang A. Tu
  • Patent number: 11680296
    Abstract: Gene expression signatures and pathways associated with tuberculosis are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for modulating tuberculosis infection. In addition, tuberculosis copy number contained in cells and methods of detecting high and low copy number are disclosed.
    Type: Grant
    Filed: October 16, 2018
    Date of Patent: June 20, 2023
    Assignee: Massachusetts Institute of Technology
    Inventors: Alexander K. Shalek, Carly Ziegler
  • Publication number: 20230183786
    Abstract: The present invention provides tools and methods for the systematic analysis of genetic interactions between cells. The present invention provides tools and methods for modulating cell phenotypes and compositions, combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.
    Type: Application
    Filed: July 19, 2022
    Publication date: June 15, 2023
    Inventors: Alexander K. Shalek, Alexander S. Genshaft, Carly G.K. Ziegler, Jeffrey F. Van Humbeck
  • Patent number: 11643669
    Abstract: The present invention relates to systems and methods for recording and assaying cellular events, in particular gene expression. The invention provides hereto a method of determining a cellular event of interest in a cell comprising providing a cell comprising a CRISPR-Cas system, wherein the CRISPR-Cas system comprises a guide RNA that targets a selected DNA sequence and a Cas protein capable of modifying the selected DNA sequence; whereby a nucleic acid molecule encoding at least one of the guide RNA or Cas protein is operably connected in the cell with a regulatory element comprising a promoter responsive to the cellular event, and whereby expression of at least one CRISPR-Cas system component is driven by the promoter; and determining cellular event of interest based on detection of the modification of the selected DNA sequence.
    Type: Grant
    Filed: December 11, 2017
    Date of Patent: May 9, 2023
    Assignee: Massachusetts Institute of Technology
    Inventors: Alexander K. Shalek, Alethe Gaillard De Saint Germain
  • Patent number: 11597964
    Abstract: The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.
    Type: Grant
    Filed: March 8, 2017
    Date of Patent: March 7, 2023
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Aviv Regev, Evan Zane Macosko, Steven Andrew McCarroll, Alexander K. Shalek, Anindita Basu, Christopher B. Ford, Hongkun Park, David A. Weitz
  • Publication number: 20230053540
    Abstract: A method of treating an injury in an organ or tissue includes administering to a subject in need thereof an agent that modulates expression and/or activity of one or more genes involved in the regeneration and functional compensation of the tissue or organ in response to the injury.
    Type: Application
    Filed: February 19, 2020
    Publication date: February 23, 2023
    Inventors: Alexander K. Shalek, Kellie Elizabeth Kolb, Chad Walesky, Wolfram Goessling
  • Patent number: 11566279
    Abstract: The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.
    Type: Grant
    Filed: January 9, 2019
    Date of Patent: January 31, 2023
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Aviv Regev, Evan Zane Macosko, Steven Andrew McCarroll, Alexander K. Shalek, Anindita Basu, Christopher B. Ford, Hongkun Park, David A. Weitz
  • Publication number: 20220404340
    Abstract: Described in certain example embodiments herein are systems, methods, and uses thereof for high-throughput in vitro evaluating multiple test compounds in parallel for biological or pharmacological functions. In certain embodiments, the system allows the selection of a subset of test compounds from a group of test compounds to form an optimized pool, and methods are provided to use such optimized pool of test compounds to identify and validate therapeutic agents for treating diseases and driving guided differentiation of stem cells into desired types of cells. The systems described herein can provide, for example, a cost-effective and high-quality high-throughput approach for drug screening.
    Type: Application
    Filed: October 23, 2020
    Publication date: December 22, 2022
    Inventors: Benjamin Mead, Conner Samuel Kummerlowe, Alexander K. Shalek
  • Publication number: 20220396777
    Abstract: In certain example embodiments, the invention provides a method of generating an ex vivo cell-based system comprising dissociating an original tissue sample obtained from a subject into a single cell population; determining an in vivo phenotype of the tissue sample by conducting single-cell RNA analysis on a first portion of the single cells; establishing an ex vivo cell-based system from a second portion of the single cells; and culturing the ex vivo cell-based system in a medium or conditions selected to maintain the in vivo phenotype. In some embodiments, the original tissue sample is a tumor tissue sample, such as a pancreatic ductal adenocarcinoma (PDAC) tumor sample.
    Type: Application
    Filed: October 26, 2020
    Publication date: December 15, 2022
    Inventors: Alexander K. Shalek, Peter Winter, Andrew Navia, Srivatsan Raghavan, William Hahn, Andrew Aguirre, Brian Wolpin, Jennyfer Galvez-Reyes
  • Publication number: 20220323406
    Abstract: The subject matter disclosed herein is generally directed to modulation of genes and pathways that drive differentiation of LGR5+ stem cells. The methods and compositions can be used to treat diseases associated with aberrant epithelial barrier function.
    Type: Application
    Filed: June 5, 2020
    Publication date: October 13, 2022
    Inventors: Benjamin Mead, Alexander K. Shalek, Jeffrey Karp, Kazuki Hattori