Search

All faculty regardless of discipline or school need to be highly competent at writing for an academic audience. The "publish or perish" pressure is alive and well for academic advancement, publications, and external grant funding. Yet few faculty, particularly in the health professions and sciences, receive formal training on the craft of writing. Faculty developers have offered a variety of programs designed to enhance the writing skills of faculty using a various formats and with varying success. Since 2006, the Indiana University School of Medicine's (IUSM) Office of Faculty Affairs and Professional Development has offered an in-depth two-day workshop plus individual tutorials designed to enhance faculty academic writing skills. This paper presents the results of an evaluation of faculty perceptions of the impact of their participation in this program. (Contains 7 tables.)

What does it take to be successful as a tenure-track research faculty member in a School of Medicine? What are the elements necessary to run a successful laboratory? How does one find the resources and help to know what is important for promotion and tenure? Most training in graduate school or in clinical fellowships does not answer these questions. Too often, new junior tenure-track research faculty members are left to learn from the "school of hard knocks" and essentially are reinventing the wheel, which is a huge waste of time. This article describes the history of research faculty, what makes them successful, and offers suggestions on how we can help them reach their greatest potential.

Faculty development programs are often at risk during difficult economic times. In order to answer the question about the value that faculty development adds to the institution, programs must measure important outcomes, not simply report the number of faculty served and how well they liked their experience. The authors describe the assessment process used at one medical school to measure change over approximately a two year time span, as well as the interventions and programs that influenced the results, with particular emphasis on women and junior faculty. Results show significant gains across all items and multiple faculty demographic groups. The findings have implications for both decisions about faculty development and assessing its impact. (Contains 1 figure and 5 tables.)

Va14Ja18 natural T (NKT) cells play an immunoregulatory role, which is controlled by a self glycolipid(s) presented by CD1d. Although the synthetic antigen [alpha]-D-galactosylceramide ([alpha]-D-GalCer) stimulates all Va14Ja18 NKT cells, [alpha]-anomeric D-glycosylceramides are currently unknown in mammals. We have used [beta]-D-GalCer-deficient mice and [beta]-D-glucosylceramide ([beta]-D-GlcCer)-deficient cells to define the chemical nature of a natural NKT cell antigen. [beta]-D-GalCer-deficient mice exhibit normal NKT cell development and function, and cells from these animals potently stimulate NKT hybridomas. In striking contrast, the same hybridomas fail to react to CD1d1 expressed by a [beta]-D-GlcCer-deficient cell line. Importantly, human [beta]-D-GlcCer synthase cDNA transfer, and hence the biosynthesis of [beta]-D-GlcCer, restores the recognition of mutant cells expressing CD1d1 by the Va14Ja18 NKT hybridomas. Additionally, suppression of [beta]-D-GlcCer synthesis inhibits antigen presentation to Va14Ja18 NKT cells. The possibility that [beta]-D-GlcCer itself is the natural NKT cell antigen was excluded because it was unable to activate NKT hybridomas in a cell-free antigen-presentation assay. These findings suggest that [beta]-D-GlcCer may play an important role in generating and/or loading a natural Va14Ja18 NKT antigen.

Neoplastic transformation of cells is accompanied by an aberration of cell surface glycolipid composition. These tumor-associated, altered glycosphingolipids are often shed into the tumor cell microenvironment and mediate immunosuppressive activity. The nature and form of glycolipids shed by a variety of tumor cell lines and the mechanism(s) of shedding have been well characterized. The murine T cell lymphoma line, L5178Y-R, is known to shed a tumor-associated glycolipid, gangliotriaosylceramide, into the culture medium. We analyzed the effect of glycolipids from L5178Y-R on antigen presentation by murine CD1d1 molecules. CD1d1 molecules present glycolipid antigens to a specialized class of T cells called natural killer T (NKT) cells that mainly express a T cell receptor [alpha] chain (V[alpha]14J[alpha]281) associated with V[beta] chains of limited diversity. In the current report, we found that L5178Y-R cells express CD1 on their cell surface yet are unable to stimulate CD1d1-specific NKT cells. We hypothesized that the glycolipid(s) shed by L5178Y-R inhibited antigen presentation by CD1d1. Pretreatment of [CD1d1.sup.+] cells with conditioned medium from L5178Y-R inhibited CD1-specific stimulation of canonical (V[alpha][14.sup.+]) but not noncanonical (V[alpha] [5.sup.+]) NKT cells. Exogenous addition of lipids extracted from L5178Y-R cells as well as purified gangliotriaosylceramide mimicked this effect. Inhibition of glycolipid shedding in L5178Y-R cells with D-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol resulted in the rescue of CD1d1 recognition by canonical (but not noncanonical) NKT cells. These results suggest that one means by which certain tumor cells can evade the host's innate antitumor immune response is by shedding glycolipids that inhibit CD1-mediated antigen presentation to NKT cells.

Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking, have rendered glioblastoma (GBM) highly resistant to therapy. To address these obstacles, here we describe a unique, sophisticated combinatorial platform for GBM: a cooperative multifunctional immunotherapy based on genetically engineered human natural killer (NK) cells bearing multiple antitumor functions including local tumor responsiveness that addresses key drivers of GBM resistance to therapy: antigen escape, immunometabolic reprogramming of immune responses, and poor immune cell homing. We engineered dualspecific chimeric antigen receptor (CAR) NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumorspecific, locally released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site-specific activity in the tissue, and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising NK cell-based combinatorial strategy that can target multiple clinically recognized mechanisms of GBM progression simultaneously. [ABSTRACT FROM AUTHOR]