Project development teams: a novel mechanism for accelerating translational research

The trend in conducting successful biomedical research is shifting from individual academic labs to coordinated collaborative research teams. Teams of experienced investigators with a wide variety of expertise are now critical for developing and maintaining a successful, productive research program. However, assembling a team whose members have the right expertise requires a great deal of time and many resources. To assist investigators seeking such resources, the Indiana Clinical and Translational Sciences Institute (Indiana CTSI) created the Project Development Teams (PDTs) program to support translational research on and across the Indiana University-Purdue University Indianapolis, Indiana University, Purdue University, and University of Notre Dame campuses. PDTs are multidisciplinary committees of seasoned researchers who assist investigators, at any stage of research, in transforming ideas/hypotheses into well-designed translational research projects. The teams help investigators capitalize on Indiana CTSI resources by providing investigators with, as needed, mentoring and career development; protocol development; pilot funding; institutional review board, regulatory, and/or nursing support; intellectual property support; access to institutional technology; and assistance with biostatistics, bioethics, recruiting participants, data mining, engaging community health, and collaborating with other investigators.Indiana CTSI leaders have analyzed metrics, collected since the inception of the PDT program in 2008 from both investigators and team members, and found evidence strongly suggesting that the highly responsive teams have become an important one-stop venue for facilitating productive interactions between basic and clinical scientists across four campuses, have aided in advancing the careers of junior faculty, and have helped investigators successfully obtain external funds

Genetic Variants Associated With Vincristine‐Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149215/1/cpt1324_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149215/2/cpt1324.pd

Obesity as a Potential Risk Factor for Vincristine Induced Peripheral Neuropathy

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Vincristine is a core chemotherapeutic agent for patients with ALL; unfortunately, approximately 78% will develop vincristine-induced peripheral neuropathy (VIPN). VIPN can result in vincristine dose reductions that decrease therapeutic efficacy: making it important to understand which children are at highest risk for VIPN. We hypothesized that pediatric ALL patients who were obese at diagnosis would develop worse VIPN than healthy weight children with ALL within the first year. Our results confirmed that obese pediatric patients have significantly (p=0.03) worse VIPN than patients of healthy weight

A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy

Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual’s quality of life. Currently, there are no established predictors of peripheral neuropathy incidence during the early stage of chemotherapeutic treatment. As a result, patients who are not susceptible to peripheral neuropathy may receive sub-therapeutic treatment due to an empirical upper cap on the dose, while others may experience severe neuropathy at the same dose. Contrary to previous genomics based approaches, we employed a metabolomics approach to identify small sets of metabolites that can be used to predict a patient’s susceptibility to peripheral neuropathy at different time points during the treatment. Using those identified metabolites, we developed a novel strategy to predict peripheral neuropathy and subsequently adjust the vincristine dose accordingly. In accordance with this novel strategy, we created a free user-friendly tool, VIPNp, for physicians to easily implement our prediction strategy. Our results showed that focusing on metabolites, which encompasses both genotypic and phenotypic variations, can enable early prediction of peripheral neuropathy in pediatric leukemia patients

Individualized exercise and the health of the AYA cancer survivor population

Objective Adolescent and young adult cancer survivors (AYACS: ages 15-39) have an 84.5% five -year survival rate. AYACS have a 10 times greater risk to develop cardiac disease compared to healthy peers. This is in part due to their lower physical activity. Structured exercise in adult cancer survivors improves strength, fatigue, VO2, and antioxidant levels and it decreases markers of cellular damage. AYACS could benefit similarly, reducing long-term health effects. Although evidence suggests exercise is beneficial in older cancer survivors, this has not been demonstrated in AYACS. We hypothesized that a 12-week one-on-one multi-modal, community-based exercise program would improve AYACS outcomes compared to baseline or inactive AYACS. The current study hopes to demonstrate the feasibility of an exercise intervention in a community setting within Indianapolis. Methods Six individuals were included in a feasibility trial for a larger pilot study of 374 participants. On day 1, baseline assessments were performed for experimental outcomes: body composition, strength, flexibility, VO2peak, balance, plasma biomarkers, PA, psychological health, health-related quality of life, and fatigue. Mini reassessments were performed at week 5, measuring strength and VO2peak with an estimated 1-rep maximum and 6-minute Walk Test respectively; in the larger pilot study participants will be reassessed at weeks 12 and 24. Participants train for 60 minutes (20 cardio, 30 weights, 10 stretching) 3 times a week for 12 weeks, one-on-one with a cancer exercise specialist. Results The average change in VO2peak was +25.3% and in strength was +17.5% (no statistical analysis). Adherence was 90.9%. Conclusions This trial suggests the feasibility of a pilot larger study. The greatest limitation was that the population sample was not within the AYACS age range. However, as the goal was to show feasibility rather than to prove efficacy, the sample gave useful information