Tufts Clinical and Translational Science Institute (CTSI) is pleased to announce the twelve recipients of the 2012 Tufts CTSI Pilot Studies awards.
Catalyst Grants
Catalyst Grants are awarded to multidisciplinary research teams of at least two investigators, representing the basic, clinical, and/or applied sciences. These collaborators must have developed a preliminary hypothesis underlying the research, and must have a defined plan for eventually seeking extramural funding. The objective of these grants is to develop sufficient preliminary data to secure future extramural funding. Awardees are:
PI: |
Miaofen G. Hu, MD, PhD, Assistant Professor, Medicine, Molecular Oncology Research Institute, Tufts Medical Center |
| Co-PI: |
Richard A. Van Etten, MD, PhD, Professor, Medicine, Molecular Oncology Research Institute, Tufts Medical Center |
| Title: |
The Role Of CDK6 In Chronic Myeloid Leukemia |
| Abstract: |
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN) induced by the oncogenic BCRABL 1-tyrosine kinase and can be effectively treated with tyrosine kinase inhibitors (TKls) such as imatinib. However, a high proportion of CML patients develop resistance to TKI treatment and suffer relapse possibly because the available therapies do not eradicate the most primitive leukemic "stem" cells that initiate and sustain the disease in vivo. Recent studies have identified cyclin-dependent kinase 6 (CDK6) as a potential target gene that synergizes with ABL 1 in leukemic transformation and whose misregulation may contribute to resistance to imatinib. However, the mechanism of CDK6-dependent leukemia formation remains unknown. (Read more) |
PI: |
Gordon S. Huggins, MD, Associate Professor, Medicine, Molecular Cardiology Research Institute, Tufts Medical Center |
| Co-PIs: |
Lauren D. Black III, PhD, Assistant Professor, Biomedical Engineering, Tufts University School of Engineering
Philip W. Hinds, PhD, Professor, Radiation Oncology, Molecular Oncology Research Institute, Tufts Medical Center |
| Title: |
Basic Mechanisms of Human Calcific Aortic Valve Disease |
| Abstract: |
Progressive calcific aortic valve disease (CAVD) is characterized by calcium deposition in the valve cusps as well as frank bone formation. People born with a bicuspid aortic valve (BAV), a common congenital heart defect, can develop significant CAVD during the prime of life. BAV and CAVD are regulated by genetic factors including mutations in the Notch1 gene. Our genetic analysis of the Tufts BAV Genetics Study identified gene variants in the WNTlb-catenin and TGFb signaling pathways, which are known to contribute to aortic valve development as well as valve calcification. (Read more) |
PI: |
Andreas K. Klein, MD, Assistant Professor, Medicine, Division of Hematology/Oncology, Tufts Medical Center |
| Co-PI: |
Raymond L. Comenzo, MD, Lecturer, Pathology, Division of Hematology/Oncology, Tufts Medical Center |
| Title: |
Characterization of A Naïve T-Cell (CD45RA)-Depleted Stem Cell Graft For Allogeneic Stem Cell Transplant With Reduced Risk For Graft-Versus-Host Disease |
| Abstract: |
Despite recent advances in targeted therapies, stem cell transplantation (SCT) remains the only treatment able to cure many of the cancers of hematopoietic origin. The success of SCT is largely limited by T-cell mediated graft-versus-host disease (GvHD), an often uncontrollable attack by the transplanted donor immune system against the recipient. T cell depletion can prevent GvHD but is problematic in that T cells have been reported to facilitate SCT engraftment, and contribute to immunity to pathogens. Therefore, it would be ideal to develop approaches that allow for successful transplants on bone marrow stem cells that contain donor T cells. (Read more) |
PI: |
Jamie L Maguire, PhD, Assistant Professor, Neuroscience, Tufts University School of Medicine |
| Co-PIs: |
Julian K. Wu, MD, FACS, Professor, Neurosurgery, Division of Neuro-oncology, Tufts Medical Center
Alain Charest, PhD, MSc, Research Assistant Professor, Neurosurgery, Molecular Oncology Research Institute, Tufts Medical Center |
| Title: |
Investigating KCC2 As A Novel Target For The Treatment Of Tumor-Associated Epilepsy |
| Abstract: |
The objective of this proposal is to investigate the role of the K+/CI- co-transporter, KCC2, in brain tumor progression and associated epileptogenesis, with the goal of identifying a novel target for therapeutic intervention. (Read more) |
PI: |
Benjamin C. Nephew, PhD, Assistant Professor, Biomedical Sciences, Section of Neuroscience and Reproductive Biology, Cummings School of Veterinary Medicine, Tufts University |
| Co-PI: |
Christopher Murgatroyd, PhD, Lecturer, Division of Health Science, School of Healthcare Science, Manchester Metropolitan University |
| Title: |
Oxytocin, Postpartum Depression and Anxiety, and Autism |
| Abstract: |
Postpartum depression impairs the maternal behavior of 15-18% of mothers, and has negative effects on spouses and children as well. Most research on depression is focused on males despite the observation that the rate of depression in females is twice the rate in males. Furthermore, studies examining the strong relationship between exposure to chronic stress and depression often use procedures and measures which are not ethologically relevant (robust physiological stressors, abstract behavioral tests). (Read more) |
PI: |
Ksenia N. Tonyushkina, MD, Assistant Professor, Pediatrics, Division of Pediatric Endocrinology, Baystate Medical Center |
| Co-PI: |
Rolf O. Karlstrom, PhD, Professor, Biology, University of Massachusetts Amherst |
| Title: |
Early Life Programming of Thyroid Axis Regulation |
| Abstract: |
Congenital hypothyroidism (CH) has nearly doubled in the last 3 decades, and defective regulation within the hypothalamic-pituitary-thyroid (HPT) axis is suspected to contribute to this growing problem. While recent studies have improved our understanding of normal development of the HPT axis, little is known about how this system matures in infants suffering from the complicated prenatal courses. (Read more) |
PI: |
Daniel E. Weiner, MD, MS, Assistant Professor, Medicine, Division of Nephrology, Tufts Medical Center |
| Co-PIs: |
Sergio Fantini, PhD, Professor, Biomedical Engineering, Tufts University School of Engineering
Tammy M. Scott, PhD, Scientist II, Nutrition and Neurocognition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging
Mark J. Sarnak, MD, MS, Professor, Medicine, Division of Nephrology, Tufts Medical Center
Aron Troen, DPhil, Visiting Scientist II, Neuroscience and Aging Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging |
| Title: |
Brain Perfusion and Cognitive Function in Hemodialysis: Effects of Acute Hemodynamic Changes |
| Abstract: |
Dialysis patients have a high cardiovascular disease burden; this affects all vascular beds in the body, including the brain, and may explain the high rates of cognitive impairment in dialysis patients. Cerebrovascular disease in dialysis patients reflects multiple factors limiting vascular autoregulation, rendering the cerebral circulation vulnerable to the hemodynamic shifts that are inherent to every dialysis session. However, we possess little knowledge regarding the effects of dialysis itself on brain structure and function. (Read more) |
PI: |
Henry H Wortis, MD, Professor, Pathology, Tufts University School of Medicine |
| Co-PIs: |
Alexander N. Poltorak, PhD, Assistant Professor, Pathology, Tufts University School of Medicine
Andrew Camilli, PhD, Professor, Molecular Biology and Microbiology, Tufts University School of Medicine
Clay Bennett, PhD, Assistant Professor, Chemistry, Tufts University School of Arts and Sciences |
| Title: |
Carbohydrate Antigen-Based Vaccine |
| Abstract: |
Protein antigens are often used in vaccines as they typically evoke potent antibody-based immunity. However, protein antigens mutate, allowing pathogens to escape immunity. Carbohydrates are attractive alternatives as mutations that alter carbohydrates are infrequent. However, the usual response to carbohydrates is low affinity antibody without memory. (Read more) |
Methods Development Grants
Methods Development Grants are awarded to investigators to develop specific methods that will advance translational research across the T1 –T4 spectrum. The proposed method is novel, and has a very high likelihood of being successfully developed within the one-year timeframe with the resources awarded. Such methods must enable an approach to research that is new, otherwise was not possible, or was less effective with current methods. Delineation of plans for future funding must be defined. Awardees are:
PI: |
Nirupa R. Matthan, PhD, Scientist II, Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging |
| Co-PIs: |
Alice H. Lichtenstein, DSc, Senior Scientist, Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging
Sarah L. Booth, PhD, Senior Scientist, Vitamin K. Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging
Kyung-Jin Yeum, PhD, Scientist I, Carotenoids and Health Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging
Judith Wylie-Rosett, EdD, RD, Professor, Epidemiology and Population Health, Albert Einstein College of Medicine, Yeshiva University and Montefiore Medical Center |
| Title: |
Impact of Acculturation Status on Dietary Patterns and Health Outcomes in Chinese Americans |
| Abstract: |
The demographic changes anticipated in the U.S. over the next decade magnify the importance of addressing health disparities among minority populations. Chinese Americans are a fast growing minority subgroup, yet there is limited and inconsistent data on the impact of dietary acculturation and subsequent cardiovascular disease (CVD) risk in this population. The goal of this proposal is to generate preliminary data for a NIH R01 grant application focused on determining the impact of acculturation status on nutrient biomarkers and CVD risk in Chinese Americans. (Read more) |
PI: |
Margie Skeer, ScD., MPH, MSW, Assistant Professor, Public Health and Community Medicine, Tufts University School of Medicine |
| Co-PIs: |
Sara C. Folta, PhD, Assistant Professor, John Hancock Research Center, Friedman School of Nutrition Science and Policy, Tufts University
Kendrin R. Sonneville, ScD, Instructor in Pediatrics, Division of Adolescent Medicine, Children’s Hospital Boston |
| Title: |
Developing An Instrument To Measure Family Meals in Relation To The Prevention Of Adolescent Risk |
| Abstract: |
Regular family meals have been associated with a reduction in certain risk behaviors in adolescence, including substance misuse, sexual risk, school failure, eating disorders, and violence. They have also been associated with increases in healthful eating habits and a reduced risk of overweight and obesity. In all fields, most studies of family meals have examined the association between family meal frequency and the various outcomes, but have not been designed to elucidate the underlying mechanisms. (Read more) |
PI: |
Howard A. Smithline, MD, MS, Associate Professor, Emergency Medicine, Baystate Medical Center |
| Co-PI: |
Khalid H. Ismail, MD, Assistant Professor, Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center |
| Title: |
Validity of Dyspnea Severity Measure in Acute Heart Failure: Pilot Study |
| Abstract: |
Acute heart failure (ACF) is the leading cause of hospitalizations in the elderly and is associated with high re-hospitalization and mortality rates. One barrier to AHF research is the lack of validated outcome measures for improvement in disease severity, including dyspnea. Dyspnea is the primary symptom associated with AHF and has been proposed as a potential primary outcome measure for AHF clinical trials. (Read more) |
PI: |
Philip N. Tsichlis, MD, Professor, Medicine, Molecular Oncology Research Institute, Tufts Medical Center |
| Title: |
NDY1/KDM2B: Development of An Enzymatic Assay And Initial Screening For Inhibitors |
| Abstract: |
Four years ago we showed that NDY1 (KDM2B, FBXL10 or JHDM1B) and NDY2 (KDM2A, FBXL11 or JHDM1A), contribute to the induction and/or progression of MoMuLV-induced T cell lymphomas in rodents. Further studies revealed that upon overexpression, both proteins immortalize MEFs in culture. Moreover, knockdown of NDY1 and expression of NDY1 dominant negative mutants promote senescence, suggesting that NDY1 is a physiological inhibitor of senescence in dividing cells. More recent studies revealed that NDY1 is induced by FGF2 and that it functions in concert with EZH2 to regulate cell proliferation, cell migration, angiogenesis and stem cell maintenance and self renewal in human tumors. (Read more) |
Congratulations to all awardees! For information on the Tufts CTSI Pilot Studies Program, go here.
