2014 INNOVATIVE CANCER RESEARCH PILOT GRANTS AWARDED
Katzen Cancer Board of Directors approves seven Innovative Cancer Research Pilot Grants for a total of $450,000.
These one-year research grants are intended to support:
1) Collaborative MFA/GWU investigators as co-PI’s with novel ideas and promising initiatives in clinical or translational cancer research, or
2) Teams of three or more investigators to conduct “synergy,” or “thematic” grants. Preference was given to teams of a proven researcher, with a successful research track record, paired with junior researchers from both GW and MFA.
The awarded grants and their researchers are:
- Prognostic Markers in Early Stage Lung Cancer: Computer Algorithms and Bayesian Regression (Clinical/Transitional) Submitted by Norris Nolan, MD and Arnold Schwartz, MD
The goal of this proposal is to build a computer algorithm to aid making reliable prognostics in early stage lung cancer. Lung cancer is typically detected at late stages ad TNM stage III or IV often associated with poor prognosis. Early stage lung cancer is however present as small lesion (a coin size lesion) named stage T1 lesion. It can be present as an isolated nodule which is not aggressive (TN1N0) or present with nodal metastases (T1N1) which is often associated with aggressive malignancy and therefore poor prognosis. But each type can be present with varying size, shape and molecular signatures that can dictate their behavior and aggressiveness. Currently for early stage lung cancer, clinicians make prognostic decision based on the pathologic staging which sometimes is personal and not accurate. The objective of this study is to develop a computerized algorithm that can integrate pathologic, environmental (tissue environment) and molecular markers to improve prognosis accuracy and decide on best treatment and care. Three aims are proposed: Aim 1: Improve the clustering based algorithm and link with current database and validate the results by testing it. Aim 2: Modify the programing for implementation on personal computer and IPads to make to facilitate use by clinicians. Aim 3: Create a logistic Bayesian regression to better assess and characterize early stage lung cancer and establish contribution of newly identified prognostic markers.
- Exploring Current Cancer Screening Rate and Testing Technological Solutions for Increase Adherence to Cancer Screening guidelines in the GW Community (Synergy) Submitted by Cherise Harrington, PhD, Neal Sikka, MD, Francis O’Connell, MD
Objective is to conduct formative work to assess rates and patterns of cancer screening to inform the development and feasibility of communication technologies to assist cancer care teams. The goal is to increase provider awareness of cancer screening guidelines, 2) increase cancer screenings, and 3) promote care coordination. This is a two-phase project with specific aims for each of two phases: a seven month needs assessment followed by development and feasibility testing of an mHealth program for use by health providers in the MFA. During Phase 1 (months 1-7), the focus is on establishing the nature of the needs for providers to improve screening practices. Will identify patterns of current practices among the GW medical community through a medical records review; conduct focus groups and structured interviews with patients and family members regarding beliefs and practices related to screening; and conduct structured interview and surveys with primary care physicians and cancer care teams to explore the provider’s perspective on patient needs for cancer screenings as well as knowledge and barriers to following clinical practice screening guidelines. During Phase 2 in months 8-12, the applicants will adapt the TEXT2KNOW platform to prompt cancer care team members to recommend appropriate cancer screenings, conduct feasibility testing of an adapted SMS/Text messaging program (adapted from the existing TEXT2KNOW platform) to prompt providers to conduct or recommend relevant cancer screenings based on clinical practice guidelines; and apply for additional funding to develop and conduct a larger effectiveness trial of the program.
- Development of Innovative Nano Dual Drug/Gene Delivery and Biometric 3D Printed Bone Model Platforms for Metastatic Breast Cancer Treatment and Analysis (Synergy) Submitted by Robert Siegel, MD, Lijie Grace Zhang, PhD, Joseph O’Brien, MD
This proposal aims to design a very novel delivery system involving rosette nanotubes (self-assembling guanine-cytosine dimers) covalently linked to a microRNA to target breast cancer cells, and within the nanotube will be a cytotoxic drug such as paclitaxel or tamoxifen. Also linked to the nanotube will be an RGD peptide motif that will act as a directing beacon to tumor cells that typically have up-regulated cell surface proteins that bind the RGD motif (i.e. integrins and CD44). The clinical relevance is obvious: i) targeted delivery to cancer cells (although this reviewer believes that other cells will likewise be targeted by the RGD domain), ii) delivery of a microRNA that can be specific to breast cancer progression/biology, and iii) the ability to more efficiently deliver very hydrophobic molecules such as paclitaxel or tamoxifen. The PI’s also propose to generate a biometric nano bone scaffolding matrix, using a 3D printer, for testing the ability of their nanotube delivery system to inhibit breast cancer cell metastasis to the biometric material -- in essence they will develop an in vitro model of bone metastasis.
- Molecular Mechanisms Reducing Predisposed Risk to Breast Cancer (Synergy) Submitted by Anelia Horvath, PhD, Rebecca Kaltman, MD, and Christine Teal, MD
This proposal aims to define the genetic and expression background accompanying BRCA1 and BRCA2 pathogenic mutations in individuals who have not developed an early onset cancer, in comparison with mutation carriers with an early onset disease. To establish: (1) genome-scale analytical platform for comparative genomic mining of BRCA1/2 mutation carriers with and without an early onset breast cancer; (2) bio-bank for intra-familial wet-lab comparative studies on BRCA1/2 positive individuals.
- Microfluidic Devices for Diagnosis and Treatment of Multiple Myeloma (Clinical/Translational) Submitted by Robert Hawley, PHD, Imad Tabbara, MD, Zhenyu Li, PhD, Irene Riz PhD, and Teresa Hawley
The identification and characterization of drug-resistant cancer stem cells is still a challenge in multiple myeloma. This research proposes to develop a novel microfluidics chip that will allow for single cell multiplexed characterization of a mixed population of cancer stem cells obtained by FACS (Fluorescence-activated cell sorting). The microfluidics chip will be able to screen up to 96 individual cancer stem cells with different cytotoxic agents. Drug resistant cells can then be forwarded into a new chamber in the device for FISH mapping to determine the exact chromosomal translocation event associated with the drug resistant cancer stem cell. There are two specific aims. Year 1 - develop microfluidics device for FISH mapping of cancer stem cells, to be followed by a Year 2 application to develop the cytotoxic drug screening chambers in the microfluidics device.
6. Concurrent Imaging and Treatment of Epithelial Cancers using Optical Coherence Tomography and Cold Plasmas: Imaging and Treatment of Excised Oral Cavity Tumors (2nd Year Continuation) Submitted by Jason Zara, PhD, Nader Sadeghi, MD
This proposal is a request for an additional stage of funding for our previously funded Katzen
project to develop a cancer imaging and treatment probe that integrates optical coherence
tomography (OCT) for imaging and cold plasmas for selective plasma treatment. During the
first project phase, PI’s were able to deliver plasmas through small tubes and developed a
prototype imaging and treatment probe, which has positioned them to be able to quickly assemble, image and treat probes for future clinical applications. PI’s also conducted a series of cell studies to investigate whether plasma-induced changes occurred in OCT images. While the
results were promising; they were not as compelling as they had hoped. PI’s believe
that this was a limitation of the tissue-mimicking cell-collagen matrix construct utilized rather
than a limitation of the plasma or OCT imaging technologies. For this reason, PI’s feel that
conducting a second round of ex vivo experiments that involve imaging, plasma treating, and
imaging of human oral cavity biopsy samples will position this work to be competitive for future
NIH R01 funding.
7. Blocking HCV Infection-Associated Hepatocellular Carcinoma with LNA-antagomiR in Mouse Model (2nd Year Continuation) Submitted by Ajit Kumar, PhD and Patricia Latham, MD
HCV infection is a leading cause of chronic hepatitis morbidity and a cause of liver cancer, hepatocellular carcinoma (HCC). Although the infection can be controlled with anti-viral medication, the long latency and attendant infection related changes are likely to be carcinogenic in many cases. The study focuses on activities of oncogenes including miRNAs whose activities appear to promote HCC in the HCV infected liver. This is a not insignificant research topic.
This proposal involves a second year continuation of a project to develop and investigate a human/mouse chimeric model of the progression of Hepatitis C Viral (HCV) infection to hepatocellular carcinoma (HCC). The project contains two aims: 1) to determine the effects of LNA-antagomiR on oncogenic gene expression in HCV infected human hepatocytes and 2) to determine the effectiveness of LNA-antagomiR in inhibiting HCV-infection HCC in a humanized mouse model.
For more information contact Leo Schargorodski at firstname.lastname@example.org or 202-741-2250.