Suzanne Craig

CCR6 Regulates the Migration of Inflammatory and Regulatory T Cells

Th17 and regulatory T (Treg) cells play opposite roles in autoimmune diseases. However, the mechanisms underlying their proper migration to inflammatory tissues are unclear. In this study, we report that these two T cell subsets both express CCR6. CCR6 expression in Th17 cells is regulated by TGF-β and requires two nuclear receptors, RORα and RORγ. Th17 cells also express the CCR6 ligand CCL20, which is induced synergistically by TGF-β and IL-6, which requires STAT3, RORγ and IL-21. Th17 cells, by producing CCL20, promote migration of Th17 and Treg cells in vitro in a CCR6-dependent manner. Lack of CCR6 in Th17 cells reduces the severity of experimental autoimmune encephalomyelitis and Th17 and Treg recruitment into inflammatory tissues. Similarly, CCR6 on Treg cells is also important for their recruitment into inflammatory tissues. Our data indicate an important role of CCR6 in Treg and Th17 cell migration.

A Butyrophilin Family Member Critically Inhibits T Cell Activation

The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells. The putative receptor for BTNL1 was found on activated T cells and APCs. Also, recombinant BTNL1 molecule inhibited T cell proliferation by arresting cell cycle progression. The administration of neutralizing Abs against BTNL1 provoked enhanced T cell activation and exacerbated disease in autoimmune and asthma mouse models. Therefore, BTNL1 is a critical inhibitory molecule for T cell activation and immune diseases.

Use of the i-STAT portable clinical analyzer in mice

The use of portable chemistry analyzers is an attractive option for obtaining clinical pathology panels in mice, because these analyzers require only small volumes of whole blood. However, in studies with other animals, portable analyzers do not always agree with results obtained using standard laboratory equipment. The authors evaluated the use of the i-STAT handheld portable clinical analyzer compared to the use of standard nonportable laboratory instruments in mice. As shown with other species, the i-STAT results did not always agree with standard laboratory instruments; however, the i-STAT does show reliability for certain chemistry assays.

Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing’s sarcoma gene (EWSR1) and the Wilms’ tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.

Chapter 6 – The Domestic Rabbit, Oryctolagus Cuniculus: Origins and History

Publisher Summary This chapter discusses the origin and the history of the domestic rabbit. All varieties of domestic rabbits used in modern biomedical research were developed from the European rabbit, Oryctolagus cuniculus. The European rabbit possesses a mixture of features that make it an appealing model for in vivo research: an intermediate body size, tractable disposition, ability to breed readily in captivity, and a short generation time. Given its obvious utility as a research subject, the European rabbit is richly represented in the scientific literature from the Age of Enlightenment onward. When breed standards improved and production facilities moved from the backyard to commercial rabbitries, rabbits were increasingly accepted as research models. The obvious physical and behavioral differences between European rabbits and other leporids ultimately led to the recognition of Oryctolagus as a separate genus, with O. cuniculus as the only member species. The role of the European rabbit as a game species, agricultural commodity, research model, invasive pest, endangered species, and companion animal has increased.Publisher Summary This chapter discusses the origin and the history of the domestic rabbit. All varieties of domestic rabbits used in modern biomedical research were developed from the European rabbit, Oryctolagus cuniculus. The European rabbit possesses a mixture of features that make it an appealing model for in vivo research: an intermediate body size, tractable disposition, ability to breed readily in captivity, and a short generation time. Given its obvious utility as a research subject, the European rabbit is richly represented in the scientific literature from the Age of Enlightenment onward. When breed standards improved and production facilities moved from the backyard to commercial rabbitries, rabbits were increasingly accepted as research models. The obvious physical and behavioral differences between European rabbits and other leporids ultimately led to the recognition of Oryctolagus as a separate genus, with O. cuniculus as the only member species. The role of the European rabbit as a game species, agricultural commodity, research model, invasive pest, endangered species, and companion animal has increased.

The Domestic Rabbit, Oryctolagus Cuniculus: Origins and History

Publisher Summary This chapter discusses the origin and the history of the domestic rabbit. All varieties of domestic rabbits used in modern biomedical research were developed from the European rabbit, Oryctolagus cuniculus. The European rabbit possesses a mixture of features that make it an appealing model for in vivo research: an intermediate body size, tractable disposition, ability to breed readily in captivity, and a short generation time. Given its obvious utility as a research subject, the European rabbit is richly represented in the scientific literature from the Age of Enlightenment onward. When breed standards improved and production facilities moved from the backyard to commercial rabbitries, rabbits were increasingly accepted as research models. The obvious physical and behavioral differences between European rabbits and other leporids ultimately led to the recognition of Oryctolagus as a separate genus, with O. cuniculus as the only member species. The role of the European rabbit as a game species, agricultural commodity, research model, invasive pest, endangered species, and companion animal has increased.Publisher Summary This chapter discusses the origin and the history of the domestic rabbit. All varieties of domestic rabbits used in modern biomedical research were developed from the European rabbit, Oryctolagus cuniculus. The European rabbit possesses a mixture of features that make it an appealing model for in vivo research: an intermediate body size, tractable disposition, ability to breed readily in captivity, and a short generation time. Given its obvious utility as a research subject, the European rabbit is richly represented in the scientific literature from the Age of Enlightenment onward. When breed standards improved and production facilities moved from the backyard to commercial rabbitries, rabbits were increasingly accepted as research models. The obvious physical and behavioral differences between European rabbits and other leporids ultimately led to the recognition of Oryctolagus as a separate genus, with O. cuniculus as the only member species. The role of the European rabbit as a game species, agricultural commodity, research model, invasive pest, endangered species, and companion animal has increased.

The Domestic Rabbit, Oryctolagus Cuniculus

Publisher Summary This chapter discusses the origin and the history of the domestic rabbit. All varieties of domestic rabbits used in modern biomedical research were developed from the European rabbit, Oryctolagus cuniculus. The European rabbit possesses a mixture of features that make it an appealing model for in vivo research: an intermediate body size, tractable disposition, ability to breed readily in captivity, and a short generation time. Given its obvious utility as a research subject, the European rabbit is richly represented in the scientific literature from the Age of Enlightenment onward. When breed standards improved and production facilities moved from the backyard to commercial rabbitries, rabbits were increasingly accepted as research models. The obvious physical and behavioral differences between European rabbits and other leporids ultimately led to the recognition of Oryctolagus as a separate genus, with O. cuniculus as the only member species. The role of the European rabbit as a game species, agricultural commodity, research model, invasive pest, endangered species, and companion animal has increased.Publisher Summary This chapter discusses the origin and the history of the domestic rabbit. All varieties of domestic rabbits used in modern biomedical research were developed from the European rabbit, Oryctolagus cuniculus. The European rabbit possesses a mixture of features that make it an appealing model for in vivo research: an intermediate body size, tractable disposition, ability to breed readily in captivity, and a short generation time. Given its obvious utility as a research subject, the European rabbit is richly represented in the scientific literature from the Age of Enlightenment onward. When breed standards improved and production facilities moved from the backyard to commercial rabbitries, rabbits were increasingly accepted as research models. The obvious physical and behavioral differences between European rabbits and other leporids ultimately led to the recognition of Oryctolagus as a separate genus, with O. cuniculus as the only member species. The role of the European rabbit as a game species, agricultural commodity, research model, invasive pest, endangered species, and companion animal has increased.

New CEO, new IACUC? New IACUC not needed.

There had been rumors for some time that the Board of Trustees was about to replace Edna Gordon as president of Great Eastern University. It wasn’t that Gordon did anything wrong; it was more that she didn’t do much of anything at all. The university had languished under her presidency and some board members had been hinting that new blood was needed. Then, unexpectedly, Gordon announced her resignation, saying that she would be leaving in six months to become the president of another academic institution. None of this raised any eyebrows on Great Eastern’s IACUC; the Committee members had seen presidents come and go over the years. For the IACUC, it seemed like business as usual, until one of the newer members raised an unusual issue. Doug Daniels, who considered himself well-versed in the federal regulations governing IACUCs, asked if there would be any change to the Committee’s membership. “No, I haven’t heard anything—but why are you asking?” said Dave Hammill, the IACUC Chairman. “Well,” said Daniels, “the Animal Welfare Act Regulations (AWRs) say that the Chief Executive Officer (CEO) appoints the IACUC, and since the new president will also be our CEO, doesn’t the new president have to reappoint the IACUC?” “I’ve never heard of anything like that,” said Hammill. “In any case, President Gordon appointed Vice-President for Research John O’Connor as the Institutional Official (IO) and you may recall that under the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy) O’Connor can appoint the IACUC as long as his delegation to do so is specific and in writing.” “Well,” said Daniels once again, “that’s only under the PHS Policy, not under the AWRs. But even under the PHS Policy, if the new CEO can delegate the authority to appoint the IACUC to the IO, I’d still like to know if O’Connor will have to be reappointed by the new president when he or she comes on board, and if O’Connor will in turn have to reappoint the IACUC.” What is your opinion on this matter? Will the new CEO (the new president) have to reappoint the IO or the IACUC? Under the AWRs, can the CEO delegate to the IO or someone else the authority to appoint the IACUC?