Michael J. Brumlik

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Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor(More)
The HER2-targeted therapy trastuzumab is widely used for the treatment of patients with metastatic breast tumors overexpressing HER2. However, an objective response is observed in only 12% to 24% of patients treated with trastuzumab as a single agent and initial responders regress in <6 months (1-3). The reason for the clinical failure of trastuzumab in(More)
Toxoplasma gondii is an Apicomplexan parasite causing significant morbidity and mortality in immunocompromised hosts. Mitogen activated protein kinases regulate diverse biologic processes including proliferation, differentiation, survival and stress responses. We searched a new T. gondii genomic database to identify a 1.6 kilobase pair (kbp) coding region(More)
An approximately 12.5-kbp region of DNA sequence from beyond the end of the previously described clavulanic acid gene cluster was analyzed and found to encode nine possible open reading frames (ORFs). Involvement of these ORFs in clavulanic acid biosynthesis was assessed by creating mutants with defects in each of the ORFs. orf12 and orf14 had been(More)
Protozoan pathogens are a highly diverse group of unicellular organisms, several of which are significant human pathogens. One group of protozoan pathogens includes obligate intracellular parasites such as agents of malaria, leishmaniasis, babesiosis, and toxoplasmosis. The other group includes extracellular pathogens such as agents of giardiasis and(More)
The Streptomyces clavuligerus clavam gene cluster was examined to identify genes specifically involved in 5S clavam biosynthesis. A reduction/loss of 5S clavam production was seen in cvm2 and cvm5 gene mutants, and a clavam metabolite not previously observed, 2-carboxymethylideneclavam, accumulated in the cvm5 mutant. Disruption of additional genes from the(More)
The parasite Toxoplasma gondii controls tissue-specific nitric oxide (NO), thereby augmenting virulence and immunopathology through poorly-understood mechanisms. We now identify TgMAPK1, a Toxoplasma mitogen-activated protein kinase (MAPK), as a virulence factor regulating tissue-specific parasite burden by manipulating host interferon (IFN)-γ-mediated(More)
The amino acid sequence of DcrA (Mr = 73,000), deduced from the nucleotide sequence of the dcrA gene from the anaerobic, sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, indicates a structure similar to the methyl-accepting chemotaxis proteins from Escherichia coli, including a periplasmic NH2-terminal domain (Mr = 20,700) separated from the(More)
Aeromonas hydrophila secretes a lipolytic enzyme that has several properties in common with the mammalian enzyme lecithin-cholesterol acyltransferase. We have recently shown that it is a member of a newly described group of proteins that contain five similar blocks of sequence arranged in the same order in their primary structures (C. Upton and J. T.(More)
All eukaryotes express mitogen-activated protein kinases (MAPKs) that govern diverse cellular processes including proliferation, differentiation, and survival. Even though these proteins are highly conserved throughout nature, MAPKs from closely related species often possess distinct signature sequences, making them well suited as drug discovery targets.(More)