IUPUI Research Day 2010

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Advanced Virtual Manufacturing Lab for Research, Training, & Education
(Office of the Vice Chancellor for Research, 2010-04-09) El-Mounayri, Hazim
The research formed a base for innovative technology that was used to develop a product on its way to commercialization. The new product provides effective and integrated tool for training and education in advanced manufacturing. It is based on sound e-learning pedagogy and highly effective and integrated virtual reality learning environment.
African American Male Success in Schooling
(Office of the Vice Chancellor for Research, 2010-04-09) Hughes, Robin L.
While there is some research addressing “gifted” African American children who attend K-12 schools (Ford, 2006; Moore III, et al., 2006), few studies address high-achieving and gifted African American male college students. Moreover, the vast majority of research highlighting the schooling of African American students focuses on their negative educational outcomes instead of their educational successes (Bonner, 2001, 2003, 2005, Bonner & Jennings, 2007; Fries-Britt, 1997, 1998, 2004; Fries-Britt & Turner, 2002; Harper, 2004, 2008). With this focus, educational stakeholders, and the students themselves, often begin thinking about within-student deficits, which, in turn, leads to expectations of failure (Hughes & Bonner, 2006; Steele, 1997). Researchers and educational institutions should highlight the successful educational characteristics of high achieving African American male students and promote success for all students. These types of research and programs might not only encourage others to think more intentionally about pushing African American students towards educational success, but more importantly, it would also encourage stakeholders to think differently about African American students and their families. This article, therefore, describes our observations of the components of a program for African American males that focuses on improving their educational success at the university level.
Analytical Redundancy Based Predictive Fault Tolerant Control of a Steer-By-Wire System Using Nonlinear Observer
(Office of the Vice Chancellor for Research, 2010-04-09) Anwar, Sohel; Niu, Wei
A nonlinear observer based analytical redundancy methodology is presented for fault tolerant control of a steer by wire (SBW) system. A long-range predictor based on Diophantine identity has been utilized to improve the fault detection efficiency. The overall predictive fault tolerant control strategy was then implemented and validated on a steer by wire hardware in loop bench. The experimental results showed that the overall robustness of the SBW system was not sacrificed through the usage of analytical redundancy for sensors along with the designed fault detection algorithm. Moreover, the experimental results indicate that the faults could be detected faster using the developed analytical redundancy based algorithms for attenuating-type faults.
Assessment of Biomedical Science Content Acquisition Performance through PBL Group Interaction
(Office of the Vice Chancellor for Research, 2010-04-09) Romito, L.
Objective: To assess the relationship between biomedical science content acquisition performance and PBL group interaction. PBL process activities should enable students to learn and apply biomedical science content to clinical situations and enhance understanding. However, learning and exam preparation may be largely driven by post-case individual study and the publicized Learning Objectives. Methods: To determine whether students were actually learning SABS content during PBL process activities, just prior to the Learning Objectives dissemination, we administered a quiz assessing content recall and application as well as a student and facilitator survey to determine students’ role in group regarding the assessed topic. Results: Year 1 mean score: content=84%; application=61%. Year 2 mean score: content=68%; application=20%. Survey response categories were: C1-those whose group did not research the topic, C2-those who did not personally research the topic, but who were in a group where the topic was researched and presented by others, and C3-those who researched the topic and contributed to/were the primary discussants. Year 2. Students scoring 100% were in: C1 (12.3%), C2 (15.5%), and C3 (15.5%). Students scoring 0% were in: C1 (30%), C2 (33%), and C3 (22%). Year 1. Students scoring 100% were in: C1 (50%), C2 (48%), and C3 (55.3%). Students scoring 0% were in: C1 (11%), C2 (9%), and C3 (2.3%). For Year 2, self-reported role in group correlated with scores of 50% (r=0.68) and 0 % (r=-0.78). For Year 1, self-reported role in group correlated with scores of 100% (r=0.78) and 0% (r=0.97). Conclusion: Year 1 and 2 students performed better on test items assessing content recall rather than application. Students who reported being more active in the PBL group process activities tended to have better assessment performance.
An atypical role for CRMP-2 in neurotransmitter release via interaction with presynaptic Ca2+ channels
(Office of the Vice Chancellor for Research, 2010-04-09) BRITTAIN, J. M.; PIEKARZ, A. D.; PIEKARZ, Y. WANG; GARCIA, A. S.; CUMMINS, T. R.; KHANNA, R.
Collapsin response mediator proteins (CRMPs) specify axon/dendrite fate and axonal growth of neurons through protein-protein interactions. Their functions in presynaptic biology remain unknown. Here, we identify the presynaptic N-type Ca2+ channel (CaV2.2) as a CRMP-2interacting protein. CRMP-2 binds directly to CaV2.2 in two regions; the channel domain I-II intracellular loop and the distal C-terminus, but not to any other regions. Both proteins colocalize within presynaptic sites in hippocampal neurons. Overexpression in hippocampal neurons of a CRMP-2 protein fused to EGFP caused a significant increase in Ca2+ channel current density whereas lentivirus-mediated CRMP-2 knockdown abolished this effect. Interestingly, the increase in Ca2+ current density was not due to a change in channel gating. Rather, cell surface biotinylation studies showed an increased number of CaV2.2 at the cell surface in CRMP-2-overexpressing neurons. These neurons also exhibited a significant increase in vesicular release in response to a depolarizing stimulus. Depolarization of CRMP-2-EGFP overexpressing neurons elicited a significant increase in release of glutamate compared to control neurons. Toxin block of Ca2+ entry via CaV2.2 abolished this stimulated release. Thus, the CRMP-2-Ca2+ channel interaction represents a novel mechanism for modulation of Ca2+ influx into nerve terminals and, hence, of synaptic strength.
The Binational/Crosscultural Health Enhancement Center
(Office of the Vice Chancellor for Research, 2010-04-09) Bergman, Alicia April; Bigatti, Silvia M.; Clark Jr., Charles M.; Everetts, David R.; Kahn, Hilary E.; Lorant, Diane Estella; Maupome, Gerardo; Mays, Rose M.; Riner, Mary E.; Snodgrass, Michael David; Soto, Armando; Stelzner, Sarah M.; Whitehead, Dawn Michele; Wilson, Gregory A.; Yoder, Karen M.
The Binational/Cross-Cultural Health Enhancement Center (BiCCHEC) fosters multidisciplinary research collaborations that address the biological, cultural, historical, legal, behavioral and demographic issues that impact the health status of communities where Latinos are born and where they live in Indiana. Since its inception, BiCCHEC projects have been multidisciplinary, 80% of the projects involve two or more IUPUI schools. BiCCHEC projects are also collaborative, 70% of the projects have one or more community partners. BiCCHEC researchers have also established a strong commitment to teaching and service, actively involving students in research (25% of current projects are student led) and servicelearning activities, developing exchange programs through our partnerships and providing direct health services in community organized events. Signature center funds have been utilized to fund internal pilot projects. The current poster will highlight four of those projects that have received pilot funding from signature center funds and have resulted in external grant applications or have already received funding, or have resulted in peer reviewed-publications. These projects are considered representative of BiCCHEC’s activities, because of their collaborative, multidisciplinary and community-based nature and include: • Study on oral health disparities using community-based participatory research • Study on the attitudes regarding children with disabilities, beliefs regarding death, coping skills and supports used during bereavement in communities in Indiana and rural Mexico • Building of a bi-national research partnership for healthful eating and diabetes prevention among Mexican and Mexican-American children • Study on emigration and return migration in 20th Century Mexico: Across the border and back again • Study on the effects of migrants' acculturation on oral health and diet in Indianapolis and Tala, Jaliscco using social network theory
Bone Resorption by Osteoclasts: Molecular Mechanism of Pyk2 dephosphorylation by Dynamin
(Office of the Vice Chancellor for Research, 2010-04-09) Eleniste, Pierre P.; Bruzzaniti, Angela
Osteoporosis is a bone disease that affects hundreds of millions of people worldwide and is characterized by low bone mass and structural deterioration of bone tissue which increases the risk of bone fracture, frailty, morbidity and mortality. Excessive bone loss is caused by osteoclasts which degrade the organic and inorganic components of bone. The specific aim of this study is to identify and characterize the signaling proteins in osteoclasts that are responsible for the bone resorbing activity of these cells. The non-receptor tyrosine kinase, Pyk2, is highly expressed in osteoclasts. Mice lacking Pyk2 have an increase in bone mass due to impairment in osteoclast function. It has been demonstrated that phosphorylation of Pyk2 at Y402 is very important for osteoclast spreading and bone resorption. Our group also reported that the GTPase dynamin controls osteoclast bone resorption in part by leading to the dephosphorylation of Pyk2, thus decreasing Pyk2’s kinase activity. In the current study we examined the intracellular mechanism by which dynamin regulates Pyk2 dephosphorylation. Our findings demonstrated that Pyk2 dephosphorylation is predominately due to GTPase activity of dynamin since expression of dynamin mutants that have reduced affinity for GTP or exhibit defective GTPase activity resulted in an increase in Pyk2 Y402 phosphorylation. We also found that that Pyk2 phosphorylation was rescued in the presence of phenyl arsine oxide (PAO), a chemical inhibitor of tyrosine phosphatases and our preliminary results indicate that the tyrosine phosphatase PTP-PEST is involved in the dynamin-mediated dephosphorylation of Pyk2. Understanding the intracellular mechanism that regulates osteoclast function may lead to the identification of novel proteins that can be targeted by anti-resorptive therapies to treat bone related diseases. Over the past few decades, bisphosphonates have played a significant role in the treatment of osteoporosis. Unfortunately, osteonecrosis of the jaw has been recently described as a harmful side effect of bisphosphonate therapy, emphasizing the need to develop alternative approaches to treat osteoporosis. Novel therapeutic approaches may one day involve inhibitors to tyrosine kinases such as Pyk2 or involve combination therapies where inhibitors are paired with bisphosphonates as a way to boost the efficacy of anti-resorptive therapies with fewer side-effects.
CELLULAR THERAPY AND HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CANCER
(Office of the Vice Chancellor for Research, 2010-04-09) Farag, Sherif S.; Srivastava, Shivani; Schwartz, Jennifer; Nelson, Robert; Homsi, Yasser; Zhang, Shuhong; Dinauer, Mary; Cornetta, Kenneth; March, Kieth; Pelus, Louis; Broxmeyer, Hal
The Center for Cellular Therapy and Hematopoietic Stem Cell Transplantation for Cancer was established in July 2007 to promote translational and clinical research in cellular therapy for cancer. The primary goal of the Center is translate discoveries from bench-to-clinic through phase I and early phase II cellular therapy clinical trials. To achieve this objective, the Center has brought together the unique expertise in hematopoiesis, immunology, gene therapy, graft engineering, and clinical hematopoietic stem cell transplantation (HCT) available at IUPUI. Since its establishment, we have completed two phase I clinical trials developing novel preparative regimens for allogeneic and autologous stem cell transplantation for patients with refractory leukemia and lymphoma, respectively. In addition, we have also initiated 5 additional early phase clinical trials that directly translate IUPUI laboratory discoveries to patients with hematological cancers. The Center has successfully competed for external funding through peerreviewed grants and pharmaceutical contracts. In this presentation, we highlight some important examples of the Center’s ongoing and completed research. An important clinical research focus of our Center is the ability to extend the curative potential of allogeneic HCT to patients without suitably HLA-matched donors. We are currently exploring ways to improve the outcomes of umbilical cord blood (UCB) and haplotype-mismatched stem cell transplantation for patients with hematological cancers. The discovery in Dr. Broxmeyer’s Laboratory, Indiana University, Indianapolis, that inhibition of the enzyme CD26 promotes homing and engraftment of limiting numbers of UCB stem cells has been translated to the first clinical trial in vivo CD26 inhibition using sitagliptin in adult leukemia patients undergoing UCB transplantation. Our preliminary data indicates that high-dose sitagliptin is well tolerated and appears to shorten the time of engraftment. As our data is further confirmed in this pilot study, we plan to investigate this potentially paradigm changing approach in a larger national study. As an extension of this research, Dr. Pelus’ Laboratory, Indiana University, Indianapolis, has shown that short-term ex vivo treatment of hematopoietic progenitors using PGE2 will also promote engraftment. We are currently investigating the potential synergy of PGE2 treatment with CD26 inhibition to further enhance engraftment, which if results appear promising will also be translated to a phase I clinical trial. In haplotypemismatched allogeneic HCT, mismatching of donor KIR receptors on natural killer (NK) cells with recipient KIR ligands expressed on the patient’s tumor cells exerts a NK cell-mediated antileukemia effect that contributes to reduced relapse after transplantation. We (Dr. Farag’s Laboratory, Indiana University, Indianapolis) have shown that in vivo donor derived NK cells developing from donor stem cells have an “inhibitory” receptor phenotype that may suboptimally function against leukemia. This has resulted in a phase I trial of purified NK cell infusion following mismatched HCT to investigate the feasibility and safety of this approach, as a prelude to a larger study to investigate its efficacy. Although the highest dose level of NK cells has not yet been investigated, the preliminary data indicates that such a novel approach is feasible. In additional studies based on our laboratory findings, we are exploring the harnessing of NK cells in the therapy of cancer through the monoclonal antibodies that block KIR receptors in combination with immuno-modulatory agents (e.g., lenalidomide) and antibodies that promote antibody-dependent cellular cytotoxicity (e.g., rituximab, anti-CS1). We have initiated patents for these discoveries, and are currently planning to transplant these into phase I clinical trials. Other ongoing research includes enhancing immune function against cancer through STAT3 inhibition to overcome tumor-mediated impairment of dendritic cell maturation, ex vivo specific expansion of cytotoxic of NK cell subsets for clinical use, and enhancing immune cell function following transplantation. The continued success of our Center will depend on a continuing pipeline of novel laboratory discoveries and their translation to early phase clinical trials to assess feasibility and safety as a prelude to larger trials assessing efficacy. Initial funding of the Center by IUPUI has allowed the Center’s conception, and the bringing together of basic and clinical researchers to the “research table” to make this translational/clinical research endeavor a reality, and has allowed us to be competitive for external funding. An important developing outcome of this initiative is the preparation for a Program Project grant in Mobilization and Engraftment of Stem Cells.
Center for Earth and Environmental Science: A Program of Excellence in Water Resources Research
(Office of the Vice Chancellor for Research, 2010-04-09) Tedesco, Lenore P.; Babbar-Sebens, Meghna
Research and training into the impacts of environmental insults on water systems and the links between water resources and human health are critical needs nationally and internationally. IUPUI is in an excellent position to take on a leadership role in scholarship and teaching about water quality and health. CEES has built its program and reputation around excellence in water resources and ecosystem restoration research. Key to our success has been the development of a research network founded on strong corporate, governmental and community partnerships and collaborations. This framework is strengthened by the mutual benefit realized by all partners and helps to support IUPUI’s core value of community engagement as an urban research university. In order to maximize the efficient use of resources, CEES is pursuing four strategic objectives in a manner that will further the universities goals of pursuing excellence in 1) research, scholarship and creative activity, 2) teaching and learning, and 3) civic engagement while also enhancing the resource base of the university. The Center places the highest priority on four strategic initiatives: 1. The Center will engage in cutting-edge research and training for mixed agricultural and urban watersheds 2. Evaluate and assess watershed Best Management Practices targeting atrazine, nutrients and emerging contaminants and pathogens 3. Establish a K-12 technology based science education program in water, air and energy 4. Work with state agencies to identify watershed issues associated with Major Moves and other economic development initiatives, the standards to be applied and training needs To this end, the Signature Center program in CEES has focused on building new collaborations with water resources and human health risks. Signature Center funding has provided for new faculty member Dr. Meghna Babbar-Sebens to join the Earth Sciences faculty as an Assistant Professor. Her research is focused on the modeling of water-borne contaminants, and decision support systems for management of water quality and associated ecological and human health risks. Dr. Babbar-Sebens research focuses on a) analysis of uncertainty when models are used to conduct spatially referenced systems-scale environmental assessments, b) incorporation of uncertainty analysis within decision support systems used for risk assessment and management, and c) optimization of water resources planning and management strategies for emergency response and water-borne disease prevention.
Center for Regenerative Biology and Medicine
(Office of the Vice Chancellor for Research, 2010-04-09) Stocum, David L.
The Indiana University Center for Regenerative Biology and Medicine (CRBM) was established at IUPUI in 2001 through a grant from the State of Indiana 21st Century Fund. In 2007, the CRBM was selected as an IUPUI Signature Center. Participating faculty come from the Schools of Science, Informatics, Medicine, and Dentistry. The Center is administered from the Department of Biology in the School of Science. Center administration consists of a Director, a Scientific Board to advise on scientific direction, and a Commercial Board to advise on technology transfer. For a complete description of the Center and its activities, see our website at www.regen.iupui.edu. Missions • Conduct multidisciplinary research aimed at understanding the mechanisms of natural regeneration, and translate the findings into regenerative therapies for tissues that fail to regenerate. • Provide graduate level academic training in regenerative biology and medicine. • Promote technology transfer. External Funding Sources CRBM faculty currently hold over $10M in research funding from a variety of Federal agencies and foundations: • NIH • NSF • NASA • W.M. Keck Foundation • Morton Cure Paralysis Foundation • American Health Assistance Foundation • American Cancer Society • Army Research Office.

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