Ralph R. Weichselbaum

Bio: Ralph R. Weichselbaum is an academic researcher from University of Chicago. The author has contributed to research in topics: Radiation therapy & Cancer. The author has an hindex of 121, co-authored 966 publications receiving 59072 citations. Previous affiliations of Ralph R. Weichselbaum include National Institutes of Health & University of Illinois at Chicago.

Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice

Abstract: High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death–ligand 1 (PD-L1, also called B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronically inflamed tissues and tumors. Here, we demonstrate that PD-L1 was upregulated in the tumor microenvironment after IR. Administration of anti–PD-L1 enhanced the efficacy of IR through a cytotoxic T cell–dependent mechanism. Concomitant with IR-mediated tumor regression, we observed that IR and anti–PD-L1 synergistically reduced the local accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs), which suppress T cells and alter the tumor immune microenvironment. Furthermore, activation of cytotoxic T cells with combination therapy mediated the reduction of MDSCs in tumors through the cytotoxic actions of TNF. Our data provide evidence for a close interaction between IR, T cells, and the PD-L1/PD-1 axis and establish a basis for the rational design of combination therapy with immune modulators and radiotherapy.

Accurate three-dimensional registration of CT, PET, and/or MR images of the brain.

Abstract: A surface matching technique has been developed to register multiple imaging scans of the brain in three dimensions, with accuracy on the order of the image pixel sizes. Anatomic information visualized in X-ray CT and magnetic resonance images may be integrated with each other and with functional information from positron emission tomography. Anatomical structures and other volumes of interest may be mapped from one scan to another, and corresponding sections through multiple scans may be directly compared. This capability provides a novel quantitative method to address the fundamental problem of relating structure to function in the brain. Applications include basic and clinical problems in the neurosciences and delivery and assessment of brain tumor therapy.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Free Radicals in the Physiological Control of Cell Function

Abstract: At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...