The CTBR awarded 8 innovation seed projects for year 2 of our program’s grant cycle. 6 of the seed projects received $20,000 for one year and 2 received $10,000 for one year due to a tied review score.
Studying cytoskeleton remodeling induced by viral protein expression
PI: Diana Bratu, Biology Department
New strategies are needed to develop efficient anti-HIV-1 therapeutics. One promising approach is to target host cell co-factors that are essential for HIV-1 viral replication, but not for cell viability. Using Drosophila melanogaster as a model system Dr. Bratu aimed to find such co-factors by combining bioinformatics, genetic, biochemical and advanced microscopy techniques. Dr. Bratu’s approach can be applied to any viral proteins not just those related to HIV-1. Dr. Bratu’s seed funding project generated data to include in an R21 grant that will be submitted in October 2013 and a publication (in preparation).
Microwave-induced thermoacoustic imaging
PI: Ying-Chih Chen, Physics Department
Dr. Chen’s long-term goal is to translate the microwave-induced thermoacoustic (TA) imaging system based on the newly available ultrashort microwave pulse technology into a medical imaging device for detection and visualization of tumors (in breast and brain), stroke-affected areas, and other features that are deeply embedded in tissues and behind bones and skulls.
Innovation of gene-targeting methods to model human disease
PI: Paul Feinstein, Biology Department
Gene-targeted animals are crucial in our understanding of the pathophysiology of human diseases and essential for testing pharmacological interventions. Dr. Feinstein’s project presents two innovative methods to optimize the existing gene-targeting technologies and to make them faster, more efficient and cost-effective. This seed funding project a produced publication:
D’Hulst, C., Parvanova, I., Tomoiaga, D., Sapar, ML., Feinstein, P. “Fast quantitative real-time PCR based screening for common chromosomal aneuploidies in mouse embryonic stem cells.” Stem Cell Reports, In Press.
Understanding the 3' untranslated region of p53 mRNA for therapeutic development
PI: Dixie Goss; Co-PI: Frida Kleiman, Chemistry Department
Breast cancer disproportionately affects minority populations. Most forms of breast cancer have defects in the p53 tumor suppression pathway. Regulation of mRNA levels after DNA damage potentially contributes to the cell rapid response to stress and control cancer development. Current strategies focus on transcriptional and post-translational induction of p53. In this proposal Drs. Goss and Kleiman focus on mRNA stability. This novel approach can potentially reveal new targets for therapeutic strategies. Drs. Goss and Kleiman are preparing preliminary data that resulted from this project to include in an R21 submission as well as future publications.
Novel Optical Detection System for Cancer Cells via Hyposmotic Deformation
PI: Hiroshi Matsui, Chemistry Department
Dr. Matsui’s project proposes to develop sensor chips that can detect lower than 5 prostate and bladder cancer cells/mL and assay cancer cells in various stages such as tumor grades 1 - 4,respectively, without using biomarkers and antigen-labeling by applying a new optical detector-incorporated sensor-in-chip. Cancer screening accomplished in various stages such as early stage, treatment process, and the disease recurrence will improve public health. The detection of cancer cells in various biological specimens with noninvasive manner economically makes this sensor platform clinically translational to bedside for disease monitoring and treatment, which is one of the most important public health issues.
Tumor-selective rapamycin analogues with clinical potential
PI: David Mootoo, Chemistry Department; Co-PI: David Foster, Biology Department
Cancer remains a major health challenge despite major advances in early detection, diagnosis and treatment. There is a demand for targeted cancer therapies that are toxic to tumors and non-toxic to noncancerous tissues. In this context, mTOR – the mammalian target of rapamycin – has been implicated in promoting cell cycle progression and survival in many human cancers. The drug rapamycin has been approved for a treatment of a small subset of cancers. The tumor targeted rapamycin analogues on which this project centers, will furnish robust, broad-spectrum antitcancer agents. The seed project resulted in two publications by the Foster Lab:
LeGendre O, Sookdeo A, Duliepre S‐A, Utter M, Frias M, and Foster DA. (2013). “Suppression of AKT phosphorylation restores rapamycin‐mediated synthetic lethality in SMAD4‐defective pancreatic cancer cells.” Mol Cancer Res. 11, 474‐481.
Saqcena M, Menon D, Patel D, Mukhopadhyay S, Chow V, and Foster DA. (2013). “Distinct nutrient‐dependent metabolic checkpoints in mammalian G1 cell cycle.” PLoS‐One. In Press.
Prostaglandin J2 hippocampal infusion to model inflammation in Alzheimer disease
PI: Maria Figueiredo-Pereira; Co-PI: Peter Serrano, Psychology Department
Alzheimer disease (AD) is a critical mental health problem as it is the most common cause of dementia. AD is a disease of disparity, affecting older African-Americans twice as much and Hispanics 1 and 1/2 times as much than older whites. Inflammation plays a central role and accelerates neurodegeneration in AD. We investigate downstream effects of inflammation to devise new strategies to prevent neurodegeneration in AD. An R01 application and a publication are in preparation to be submitted in Fall 2013 and next year, respectively.
Integrated Neurobiological Mechanisms of PTSD Symptoms
PI: Mariann Weierich, Psychology Department
More than half of the US population will be exposed to a traumatic event at some point in their lives, and the estimated lifetime prevalence of posttraumatic stress disorder (PTSD) in the US is 6.8%. In addition, PTSD symptoms contribute to new vascular problems and decreases in general physical functioning. PTSD is a significant public health problem, not only due to increased need for psychological services, but also through decreased work productivity and increased need for healthcare. The broad, long-term objective of Dr. Weierich’s project is to identify candidate neurobiological mechanisms and related factors that can enhance precision and cost-effectiveness in the diagnosis and treatment of posttraumatic stress disorder. The short-term goal of this project is to begin to develop an integrated model of several candidate mechanisms by testing their actions and interactions in adults with trauma exposure. Preliminary data generated from this seed funding project will be included in an upcoming R03 application.