Thursday, April 6, 2017

By Nicholas Snow

The Rose Mercadante Chemistry Seminar series is pleased to present the final PhD seminar of Mariana Phillips, entitled "B7H6 Derived Peptides Trigger TNF- Dependent Immunostimulatory Activity of Lymphocytic NK92-MI Cells."

The seminar will be held at 5:45 p.m. on Tuesday April 11, 2017 in the Helen Lerner Amphitheater, McNulty Hall, Science and Technology Center, Seton Hall University. The University Community is invited.

Mariana Phillips was born in Mexico City, Mexico where she received her BSc in Food Chemistry from Universidad LaSalle, Mexico, in 1998. Phillips's academic career began as a science teacher of Physics and Chemistry, focusing particularly on developing a stimulating scientific learning environment for middle school students. Phillips relocated to the United States in 2005 with her family to pursue new scientific career goals. In 2012, she joined the Department of Chemistry and Biochemistry at Seton Hall University, to work on her PhD under the supervision of Profs. David Sabatino and Constantine Bitsaktsis. During her PhD studies, Phillips has developed methods in chemical biology for the production of novel immunstimulatory peptides. Phillips has also gained expertise in working with protein biologics, including antibody mimics for cancer-targeting immunotherapy applications. In 2015, Phillips received her MS degree in Biochemistry following her successful matriculation into the PhD program. In 2016-17, Phillips initiated a productive research collaboration with Dr. Robert Korngold at Hackensack UMC to investigate the biological properties of immunstimualtory constructs in vitro and in vivo. Taken together, Phillips accomplishments during her PhD studies have led to the generation of two publications, a book chapter currently in press, a research grant approved for funding, a travel grant award for attending the American Peptide Symposium in 2015 and more than five presentations and proceedings at local and national conferences. Phillips expects to receive her PhD in Biochemsitry in May 2017.

B7H6 has been identified as a cellular membrane protein expressed exclusively on tumor cells. Interestingly, B7H6 was found to bind selectively to NKp30, an activating receptor expressed on NK cells. B7H6:NKp30 binding stimulates NK cells' antitumor immune responses through the release of cytotoxic cytokines and chemokines, leading to tumor cell death. However, lower levels or the absence of cell surface B7H6 have correlated with the evolution of tumor resistance towards NK cells' immunosurveillance. Therefore, new B7H6 derived ligands that can bind and activate NK cells are expected to improve NK-dependent killing of resilient tumors. Towards this goal, this thesis work describes the rational design of a novel class of immunostimulatory peptides (IPs) derived from the binding site interface of B7H6:NKp30. The IPs were synthesized by conventional Fmoc solid phase peptide synthesis which also facilitated the incorporation of N-terminal fluorescein isothiocyanate (FITC) for structure-activity relationship studies. The secondary structures of the peptides were examined by CD spectroscopy which revealed versatile peptide structures which transitioned from random coil to -helical and turn-type conformations. Their biological properties were evaluated by flow cytometry, enzyme-linked immunosorbent assays (ELISAs) and cell death assays. The immunostimulatory effects of the IPs on the human NK92-MI cells were assessed by the production of TNF- alone as IFN- was undetectable. In a cell death assay, the IPs were found to be non-toxic, without any observable evidence of early or late stage apoptosis within the NK92-MI cells. Therefore, B7H6 derived peptides encompass an interesting class of ligands for activating NK cells' immune activities. The latter is a current focus of our on-going research program in cancer immunotherapy applications.

The Department of Chemistry and Biochemistry offers BS, MS and PhD degrees with specializations in all areas of chemistry. Our unique research environment, including traditional full-time students and part-time students is designed to foster collaborations with industry and colleagues in other disciplines. The Rose Mercadante Seminar Series is named for Rose Mercadante, the departmental secretary for over 40 years, in honor of our alumni, her "boys and girls".

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