University of Michigan

Other

University of Iowa Research Foundation

Max S Wicha

Michael F Clarke

Muhammad Al-Hajj

Sean J Morrison

Christophe Ginestier

Diane M Simeone

Sunitha Nagrath

Hyeun Joong Yoon

Suling Liu

Lianette Rivera Baez

Eric Lin

Euisik Yoon

Michael K Schultz

Douglas R Spitz, Jr

Riley Brien

Hasan Korkaya

Gabriela Dontu

Emmanuelle Charafe-Jauffret

Yu-Heng Cheng

Yu-Chih Chen

Kyle Kloepping

Yueming Zhu

Nukhet Aykin-Burns

Sean J Univ Of Michigan Med School Morrison

Muhammad Dept Of Internal Medicine Al-Hajj

The present disclosure relates to systems and methods for whole cell analysis. In particular, the present disclosure relates to single cell genomic analysis (e.g., gene expression analysis.

Systems and methods for whole cell analysis

A microfluidic device for detecting rare cells in a fluid sample comprises the rare cell and other cells. The microfluidic device comprises an inlet for receiving the fluid sample, a labyrinth channel structure in fluid communication with the inlet, and an outlet in fluid communication with the labyrinth channel structure for collecting the rare cells separated from the other cells in the fluid sample. The labyrinth channel structure comprises at least one channel through which the fluid sample flows. The at least one channel has a plurality of segments and a plurality of corners with each corner defined between adjacent segments. The presence of the plurality of corners induces separation of the rare cells from the other cells in the fluid sample as the rare cells move to a first equilibrium position within the at least one channel when a ratio of inertial lift forces (F) and Dean flow (F) of the fluid sample is from 2 to 10.

Microfluidic device and method for detecting rare cells

The present invention provides methods of treating cancer by administering an IL8-CXCR1 pathway inhibitor (e.g., an anti-CXCR1 antibody or Repertaxin) alone or in combination with an additional chemotherapeutic agent such that non-tumorigenic and tumorigenic cancer cells in a subject are killed. The present invention also provides compositions and methods for detecting the presence of and isolating solid tumor stem cells in a patient (e.g., based on the presence of CXCR1 or FBXO21).

Anti-CXCR1 compositions and methods

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Isolation and use of solid tumor stem cells

The invention provides compositions and methods to treat cancer with an agent that increases reactive oxygen species (ROS) levels in cancer cell mitochondria ('an XTPP agent') or a pharmaceutically acceptable salt thereof, an inhibitor of hydroperoxide metabolism and a pharmaceutically acceptable diluent or carrier.

Compositions and methods of treating cancer

Methods of detecting and treating stem-cell containing solid tumors

A small percentage of cells within an established tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Compositions, kits, and methods for therapeutic screening, diagnostics, and cancer treatment based on the identification or use of the different states of cancer stem cells, including cancer stem cells in the EMT (epithelial to mesenchymal transition) MET (mesenchymal to epithelial transition), and EMT-MET states are disclosed. In some methods, a subject is treated with one therapeutic that targets EMT cancer stem cells and a second therapeutic that targets MET cancers stem cells. In certain methods, the different states of cancer stem cells are distinguished based on markers CD44+CD24&#x2212;, EpCam&#x2212;CD49P+ (for EMT cancers stem cells), ALDH+ and EPCam+CD49r&#x2212; (for MET cancers stem cells), and CD44+CD24&#x2212;ALDH+ (for EMT-MET cancer stem cells). In particular methods, micro RNAs are used to transition to one particular cancer stem cell type (e.g., mir-100 for EMT and mir-93 for MET).

Method of reducing the number of EMT and MET type breast cancer stem cells

The present invention relates to compositions, methods, and kits for treating cancers with HER2 targeting agents and preventing resistance thereto. In particular embodiments, non-HER2-amplified cancers are treated with HER2 targeting agents, wherein the cancer stem cells in the cancer express HER2 and/or HER2 indicator marker. The present invention also relates to compositions, methods, and kits for detecting expression of HER2 and/or a HER2 indicator marker in non-HER2-amplified cancer samples from a subject, and identifying the subject as responsive to treatment with a HER2 targeting agent and/or treating the subject with a HER2 targeting agent.

HER2 targeting agent treatment in non-HER2-amplified cancers having HER2 expressing cancer stem cells

The invention provides methods for treating cancer via administering to a patient having a solid tumor a therapeutically effective amount of an antibody against Delta-like ligand 4(Dll4) or other Notch pathway components. The solid tumor may comprise solid tumor stem cells.

Method for treating cancer using an antibody that inhibits notch4 signaling

Breast tumor treatment with anti-CXCR1 compositions

The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides a novel stem cell cancer marker, ALDH1, useful for the diagnosis, characterization, and treatment of solid tumor stem cells.

Aldehyde dehydrogenase 1 (ALDH1) as a cancer stem cell marker

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise to both more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

A small percentage of cells within an established solid tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

Growing community of inventors

Ann Arbor, MI, United States of America

Max S Wicha