Janet V. Cross - US grants

[unreadable] DESCRIPTION (provided by applicant): Fresh fruits and vegetables are the foundation of a healthy diet. They not only provide vitamins and minerals that are essential for human health, but they also contain bioactive nutrients that have demonstrated efficacy in preventing cancer in animal models. While this phenomenon of cancer chemoprevention is well appreciated, the mechanism by which these bioactive nutrients bring about these effects remains obscure. Moreover, the possibility of other, more subtle health benefits arising from these bioactive nutrients has been mostly ignored. [unreadable] [unreadable] One class of chemopreventive compounds, the bioactive nutrient isothiocyanates (ITCs), are abundant in cruciferous vegetables such as broccoli, and have a chemical structure that suggest that they could covalently react with proteins in the cell. In an effort to further understand the mechanism of action of these chemicals, we undertook a screen to isolate protein targets of bioactive nutrient ITC modification. We isolated a predominant target of this class of bioactive nutrients that is a critical mediator of inflammatory disease processes. Modification by nutritional ITCs inhibits the enzymatic activity of this protein, suggesting bioactive nutrient ITCs may inhibit the downstream functions of the protein that drive inflammation. [unreadable] [unreadable] We propose that the degree of bioactive nutrient ITC modification of this protein may represent a valuable surrogate biomarker of effective delivery. Modification of this protein represents a measure of bioavailability that can be applied not only to biological fluids, but also to potential target tissues. We present experiments designed to develop this biomarker as a means to examine the bioavailability and trace the pharmacokinetics and pharmacodynamics of bioactive nutrient ITCs in an intact animal. [unreadable] [unreadable] In addition, we propose that the bioactive nutrient ITCs may have previously unappreciated anti-inflammatory benefits as a result of their ability to modify and inhibit this critical mediator of inflammation. We will examine this possibility using a classical model of inflammation in combination with animals deficient in this protein target. These studies will allow us to both probe the potential anti-inflammatory properties of bioactive nutrient ITCs, as well as define a potential molecular mechanism for their effectiveness. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): We propose to continue an existing and highly successful Summer Research Internship Program (SRIP) at the University of Virginia School of Medicine. The goals of this program will be to expose a diverse group of undergraduate students and medical students to state of the art Biodefense and Infectious Diseases research, to instill in them confidence and a desire to consider research as a career option, and to familiarize them with the opportunities that exist for a career in biomedical research. The program runs for ten weeks each summer and is multi-faceted. The first and most important facet involves student exposure to and participation in a contemporary research project under the guidance of a faculty member. A second facet has the students participating in a series of weekly workshops in which students are exposed to a variety of advanced research techniques that they are unlikely to see in individual laboratories, including the use of confocal and electro microscopy, bioinformatics, genomics and proteomics, genetic mapping techniques, hybridoma/monoclonal antibody preparation, etc. The third facet includes a series of lectures and discussions wherein the students are exposed to a wide array of research topics and internationally recognized scientists. These scientists include women and underrepresented minority scientists who can serve as role models for these students. Finally, a fourth facet of our program is a weekly research lunch co-hosted by the principal investigators Drs. Petri and Hockensmith, during which the students give oral statements of their working hypotheses, summaries of the past week's research progress, discuss career options and opportunities, and consider approaches for choosing and applying to a graduate program. Nearly 40 faculty members, whose principal research interests are in Biodefense and Infectious Diseases, will serve as mentors. All components of this program are currently in place. In summary, we feel that our program provides an outstanding environment to stimulate and foster interest in research careers in biomedical research. Reviews of the program by past participants have been outstanding and have contributed significantly to the continued interest in our program.

DESCRIPTION (provided by applicant): We propose to continue an existing and highly successful Summer Research Internship Program (SRIP) at the University of Virginia School of Medicine. The goals of this program will be to expose a diverse group of undergraduate students and medical students to state of the art Cardiovascular, Hematologic and Pulmonary Diseases research, to instill in them confidence and a desire to consider research as a career option, and to familiarize them with the opportunities that exist for a career in biomedical research. The program runs for ten weeks each summer and is multi-faceted. The first and most important facet involves student exposure to and participation in a contemporary research project under the guidance of a faculty member. A second facet has the students participating in a series of weekly workshops in which students are exposed to a variety of advanced research techniques that they are unlikely to see in individual laboratories, including the use of confocal and electron microscopy, bioinformatics, genomics and proteomics, genetic mapping techniques, hybridoma/monoclonal antibody preparation, etc. The third facet includes a series of lectures and discussions wherein the students are exposed to a wide array of research topics and internationally recognized scientists. These scientists include women and underrepresented minority scientists who can serve as role models for these students. Finally, a fourth facet of our program is a weekly research lunch co-hosted by the principal investigators Drs. Owens and Hockensmith, during which the students give oral statements of their working hypotheses, summaries of the past week's research progress, discuss career options and opportunities, and consider approaches for choosing and applying to a graduate program. Nearly 70 faculty members, whose principal research interests are in Cardiovascular, Hematologic or Pulmonary Diseases, will serve as mentors. All components of this program are currently in place. In summary, we feel that our program provides an outstanding environment to stimulate and foster interest in research careers in biomedical research. Reviews of the program by past participants have been outstanding and have contributed significantly to the continued interest in our program. (End of Abstract)

ABSTRACT The goal of the Summer Medical Research Internship (SMRI) is to exploit the rich research community at the University of Virginia (UVA) to expose medical students to the excitement, capabilities, rigors, and breadth of opportunities for careers in allergy and infectious diseases research. From its inception, the major goals of this NIAID-supported program have been to: (1) provide a high-quality, immersive, hands- on research experience in allergy or infectious diseases, igniting the passion of the next generation of physician-scientists; (2) introduce trainees to the rich synergy between basic research and clinical care; (3) instruct trainees on how to communicate about scientific discovery to audiences with different backgrounds and levels of expertise; and 4) inform trainees about different approaches through which research can be successfully incorporated into a career in clinical medicine, with an overarching goal of kindling and nurturing a passion for doing research that truly makes a difference and leaves a mark on mankind. This application seeks support to continue this successful program, through which ten (10) medical students will be supported each year. The ten-week program has three educational components. The first and most important is an immersive, hand-on research experience mentored by of one of our 52 program faculty and focused in the mission areas of the NIAID. Second, the trainees participate in a weekly 1-hour workshop focused on developing and refining written and oral scientific communication skills appropriate for various contexts and audiences. Finally, the trainees attend a weekly professional development luncheon series. One part of this series, titled ?Conversations with a Physician-Scientist,? features faculty who have each taken a different approach to incorporating research into their career in clinical medicine. The second part is a seminar series which features highly successful researchers from across the UVA community, who present their research and discuss their career path. Through strong mentorship, hands-on research, innovative educational initiatives, and exposure to a wide range of perspectives on combining research and clinical interests, trainees in the SMRI are uniquely prepared to pursue advanced training with the ultimate goal of becoming members of the physician-scientist workforce. !

ABSTRACT Our goal with the ten-week Summer Research Experience in Cancer (SuRE-C) Program is to exploit the rich cancer research community at the University of Virginia to expose undergraduate and medical students to the excitement, capabilities, rigors, and breadth of opportunities for careers in cancer research. Fifteen (15) undergraduate and/or post-baccalaureate students and five (5) incoming first- or rising second-year medical students will be enrolled in SuRE-C each year. The program has four educational components. The first and most important is a hands-on cancer research project that will be performed under the mentorship of one of our 47 program faculty. Second, we will take advantage of our close association with the NCI-designated UVA Cancer Center to provide the trainees with opportunities to learn about the challenges in cancer care and interact with cancer patients. Third, trainees will participate in a weekly 1-hour workshop focused on developing and refining scientific communication skills appropriate for various contexts and audiences. Finally, the trainees will attend a once-a-week professional development luncheon series that will provide instruction in approaches to cancer research and panel discussions of career options led by current and former students, fellows, faculty, physician scientists, and clinical trialists. These presentations will be intertwined with practical experiences focused on positioning both the undergraduate and medical student trainees for success at the next stages of their career. The program will undergo a robust evaluation process to assess whether it is meeting its goals. Through strong mentorship, hands-on cancer research, innovative educational initiatives, and exposure to a wide range of cancer-related research and clinical care experiences, trainees in the SuRE-C Program will be uniquely prepared to pursue advanced training in a variety of specialties with the ultimate goal of becoming members of a diverse biomedical workforce in cancer-research. !