University of Iowa Research Foundation

Synderbio, Inc.

Michael D Henry

J Matthew Barnes

Kevin P Campbell

Benjamin L Krog

Sarah C Vigmostad

Roger Williamson

Michael B Cohen

Michael Oldstone

Eric Leopold

Hiroki Yamada

Wei Cao

Michael Cable

Rupesh Desai

Mike Cable

In some embodiments, the present disclosure provides an apparatus and methods for selectively lysing cells from a cell suspension including disassociating a population of cells from a tissue sample, the population of cells including a population of one or more viable cells and a population of one or more dead and dying cells, exposing the population of cells to at least one pulse of fluid shear stress having a force along a conduit wall of from about 500 dyn/cm2 to about 2500 dyn/cm2 to substantially lyse the population of one or more dead or dying cells, leaving the population of one or more viable cells substantially intact, and collecting the population of one or more viable cells.

Method and apparatus for selective removal of cells from a cell suspension by mechanical lysis

Methods for isolating viable cancer cells from a sample that comprises a mixture of cancerous cells and normal (non-cancerous) cells are provided. In the methods, a fluid preparation comprising a mixture of cancerous and normal cells is repeatedly exposed to fluid shear stresses, whereby the repeated exposure to the fluid shear stresses preferentially imparts fluid shear stress-resistance to the cancerous cells.

Method of purifying tumor cells using shear stress

A fluid handling system for applying a plurality of pulses of fluid shear stress to a fluid sample may comprise a first sample chamber; a second sample chamber; a plurality of conduits mounted between and in fluid communication with the first sample chamber and the second sample chamber; and a force delivery system mounted to the first sample chamber and configured to apply a force sufficient to push the fluid sample from the first sample chamber through each of the conduits at a substantially constant flow rate to the second sample chamber. The plurality of conduits may be arranged in series and separated by additional sample chambers or arranged such that the conduits are substantially parallel to one another. The force delivery system may be a gas delivery system or a linear drive assembly.

Fluid handling systems for application of fluid shear stress to a fluid sample

Isolation and characterization of tumor cells using shear stress measurements

Disclosed is a method for diagnosing the tumorigenic grade of a malignant tissue. The method entails determining the amount of dystroglycan protein of the malignant tissue relative to a standard. Suitable methods for determining the amount of dystroglycan protein of the tissue are provided, and include measuring the amount of mRNA transcripts which encode dystroglycan, and also performing western blot analysis or immunofluorescence analysis on the tissue components to detect &agr;-dystroglycan or &bgr;-dystroglycan. An antibody probe which binds specifically to the C-terminus of &bgr;-dystroglycan, is provided. This method is applicable to human malignant tissue, especially adenocarcinoma, and preferably prostate or mammary adenocarcinoma. This method can also be applied to the detection of a cancerous disease state in a tissue of a patient, with a decreased level of dystroglycan protein being indicative of the presence of cancer. Also disclosed is a method for determining the prognosis of a patient afflicted with a malignancy by determining the expression level of the dystroglycan gene in a tissue sample of the malignancy, and comparing the expression level to a standard, with a decreased level of dystroglycan expression being indicative of unfavorable prognosis. A method for identifying an individual at risk for the development of cancer, or an individual at risk for the recurrence of cancer after treatment, is also disclosed. Similarly, a method for identifying individuals at risk for developing cancer by screening for mutations in the dystroglycan genes of the individual is also provided. One such mutation is the allelic loss of human chromosome 3p21.

Evaluation of adenocarcinoma of the prostate and breast using anti-dystroglycan antibodies

Disclosed is a method for inhibiting the binding of an arenavirus to a cellular receptor. The method involves providing, in soluble form, a reagent comprising .alpha.-dystroglycan or a portion thereof, the reagent being characterized by the ability to bind to the arenavirus thereby inhibiting the binding of the arenavirus to the cellular receptor. The reagent is contacted with an arenavirus particle prior to infection of a cell by the arenavirus particle. Also disclosed are methods for treating an arenavirus infection in a patient and preventing an arenavirus infection in an individual at risk. These methods involve providing a therapeutic composition comprising .alpha.-dystroglycan or a portion thereof which is characterized by the ability to bind to arenaviruses, thereby inhibiting the binding of arenaviruses to a cellular receptor; and administering the composition to the patient or individual at risk. Arenaviruses to which the methods of the present invention apply include, without limitation, Lymphocyte Choriomeningitis Virus, Lassa fever virus, Mobala, and Oliveros. In another aspect, the disclosure relates to an embryonic stem cell line, and cells derived therefrom, which is homozygous for a disrupted dystroglycan gene, wherein the disruption prevents the synthesis of functional dystroglycan in the cells. Applications of the dystroglycan null embryonic stem cells include producing dystroglycan or a portion thereof in the cells and also for identifying portions of dystroglycan necessary for arenavirus infection. Also disclosed is a method for identifying antiviral compounds which interfere specifically with the binding of arenavirus and .alpha.-dystroglycan, comprising providing a binding assay system for the determination of binding of arenavirus and .alpha.-dystroglycan. The candidate antiviral compounds are introduced into the binding assay system and antiviral compounds which substantially inhibit binding of arenavirus to .alpha.-dystroglycan are identified.

Arenavirus receptor and methods of use

Growing community of inventors

Iowa City, IA, United States of America

Michael D Henry