2010-2011 Pilot Project Awards

The awardees and their projects are:

     
 
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Brian E. Brigman, MD, PhD 
 Assistant Professor of Surgery and Pediatrics, Duke University Medical Center

Clinical Development of an Intraoperative Imaging System for Detection of Residual Cancer in the Tumor Bed

Technology that can determine whether cancer cells remain in the body in a real-time, live operative setting has the potential to have a profound impact on the practice of surgical oncology. Incomplete resection of malignant tumors is a leading risk factor for local recurrence, poorer clinical outcomes, and the need for additional local therapies.

The goal of this proposal is to test whether a hand-held intraoperative imaging device can detect microscopic residual cancer in canine patients in a veterinary clinical trial.  The device will be used with a fluorescent imaging agent to obtain intra-operative molecular images during surgical removal of soft-tissue sarcomas from canine companions.

Co-Investigators:

  • David G. Kirsch, MD, PhD, Associate Professor in Radiation Oncology and Assistant Professor in Pharmacology and Cancer Biology, Duke University Medical Center
  • William C. Eward, MD, DVM, Resident in Orthopaedic Surgery, Duke University Medical Center; Associate Veterinarian, Veterinary Specialty Hospital of the Carolinas
 
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James O. McNamara, MD
Carl R. Deane Professor and Chairman, Department of Neurobiology, and Director, Center for Translational Neuroscience, Duke University Medical Center

Inhibitors of Epileptogenesis

Temporal lobe epilepsy (TLE) accounts for 40 percent of adult cases. It progresses to refractoriness to anticonvulsant medication in 30 percent of cases. There is no effective prevention or cure, apart from surgery for a minority.  Our in-vivo studies suggest that TrkB-dependent activation of phospholipase Cy1 (PLCy1), signaling is an important molecular mechanism underlying seizure induced progression of epilepsy.

We will partner with Drs. Haian Fu and Ray Dingledine in the Chemical Biology Discovery Center at Emory University to use combinatorial libraries in conjunction with a novel protein/protein-interaction high through-put screening approach to identify chemically distinct inhibitors of the interaction of TrkB with PLCyl. 

Co-Investigators:

  • Rodney A. Radtke, MD, Professor of Medicine (Neurology), and Director, Clinical Neurophysiology, Duke University Medical Center
  • Raymond Dingledine, PhD, Professor and Chairman, Department Of Pharmacology, Emory University School of Medicine
  • Haian Fu, PhD, Professor of Pharmacology, Hematology/Medical Oncology, Emory University School of Medicine.
     
 
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Carmelo A. Milano, MD
Associate Professor of Surgery, and Surgical Director of Cardiac Transplantation and LVAD Programs, Duke University Medical Center

Expansion of the Cardiac Allograft Donor Pool by Resuscitation of Human Donation after Cardiac Death (DCD) Donor Hearts

 

Orthotopic heart transplantation is a successful treatment to end-stage heart failure, but this therapy is severely constrained by the limited donor supply, particularly for pediatric patients.

An alternative option to the current donor hearts obtained from brain dead donors is the use of donation after cardiac death (DCD) hearts from severely brain injured patients, acquired after withdrawal of mechanical ventilation and cardiopulmonary arrest. DCD hearts could increase the donor pool by up to 20 percent, but are not currently used due to the risk of ischemia-reperfusion injury and subsequent primary graft dysfunction. 

This project will investigate the controlled reperfusion of explanted DCD hearts in an ex vivo heart perfusion system (currently in pre-clinical development by a biomedical company). Biochemical and functional assessment of human and porcine DCD hearts will then be performed to define the cardiac injury biomarker levels that predict successful resuscitation and transplantation of the DCD heart.  

 

Co-Investigators/Collaborators:

  • Andrew J. Lodge, MD, Assistant Professor of Pediatrics, Duke University Medical Center
  • Dawn E. Bowles, PhD, Assistant Professor of Surgery, Duke University Medical Center
  • Valentino Piacentino III, MD, PhD, Research Associate
 
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Duane A. Mitchell, MD, PhD
Assistant Professor of Surgery (Neurosurgery), Duke University Medical Center

Clinical Development of a Therapeutic Peptide Vaccine Targeting Glioblastoma

 

Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor in humans. It has recently been discovered that the majority of GBMs (>90 percent) are associated with tumor-restricted reactivation of human cytomegalovirus (CMV).  

Temozolomide (TMZ), a methylating chemotherapeutic agent, has shown efficacy in patients with newly diagnosed GBM, but it induces a profound lymphopenia that may inhibit any anti-tumor immune response. The investigators previously demonstrated that dendritic cell-based vaccination targeting the immunodominant CMV antigen pp65 produces an immune response in patients with GBM undergoing standard of care TMZ treatment. 

The goal of this project is to further boost this immunologic response through the development and administration of a CMV-specific peptide cocktail to patients recovering from TMZ treatment-induced lymphopenia. The investigators will conduct a Phase I clinical trial to determine if this vaccination is safe and leads to immune responses directed against CMV antigens in patients with newly diagnosed GBM.

 

Co-Investigators/Collaborators:

  • John H. Sampson, MD, PhD, Associate Professor of Surgery, Assistant Professor of Pathology, and Associate Deputy Director of The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
  • David A. Reardon, MD, Associate Professor of Surgery, Associate Professor of Pediatrics, and Associate Deputy Director of The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center.
  • James E. Herndon II, PhD, Associate Professor, Duke University Medical Center
  • Kent J. Weinhold, PhD, Professor of Immunology and Surgery, Duke University Medical Center.
 
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Matthew Reynolds, PhD
Assistant Professor, Department of Electrical and Computer Engineering, Duke University

Improving Hand Hygiene Compliance with RFID Monitoring

More than 50 percent of complications that occur during hospitalization are  due to infection. The primary cause of nosocomial infections has repeatedly been identified as the contact transmission of infective agents on the hands of healthcare workers.

A data collection system based on radio frequency identification (RFID) technology has the potential to automatically collect hand hygiene compliance data. This compliance data can objectively inform healthcare worker management and ultimately reduce the nosocomial infection rate. 

The investigators will develop a device to report the usage of a hand hygiene product by individuals in the laboratory environment.  The device will be tested in a clinical setting to validate the data reported by the device with participating clinical providers that “opt in” by agreeing to affix an RFID label to the back of their badge.

 

Co-Investigators:

  • Andrew D. Munro, MD, Resident, Department of Ophthalmology, Duke University Medical Center
  • David K. Wallace, MD, MPH, Associate Professor, Department of Ophthalmology, Duke University Medical Center
 
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John H. Sampson, MD, PhD
Associate Professor of Surgery, Assistant Professor of Pathology, and Associate Deputy Director of The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center

Agonist Aptamers as Immunotherapy Adjuvants for Gliobastoma

Glioblastoma multiforme (GBM) remains nearly universally fatal, and conventional treatments cause damage to normal tissue. However, the immune system has the unique ability to specifically eliminate abnormal cells while leaving adjacent normal cells untouched. In an effort to enhance vaccine-mediated anti-tumor immune response, the investigators have developed multivalent agonist RNA aptamers that bind to potent co-stimulatory molecules expressed on the surface of T-cells.

This project will study the efficacy of these aptamers in murine brain tumor models. Additionally, cross-reactive murine and human aptamers will be developed to provide pre-clinical and toxicity data to support an IND submission and enable a Phase I clinical trial.

 

Co-Investigators:

  • Smita Nair, PhD, Assistant Professor, Immunotherapy in Cancer and AIDS, Duke University Medical Center
 
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John S. Sundy, MD, PhD
Associate Professor of Medicine, Pulmonary and Critical Care Medicine
Director, Duke Clinical Research Unit (DCRU)
Director, Immunology and Inflammation Medicine (DCRI)
Director, American Lung Association Asthma Clinical Research Center, Duke University Medical Center

Strategies for Enhancing Mucosal Immunity to Influenza Vaccine

The ability to manipulate the immune response within mucosal tissues such as the respiratory, gastrointestinal and genital tracts is a critical therapeutic need. Most human vaccines are administered by intramuscular or subcutaneous injection, and typically do not induce antigen-specific immune responses in mucosal tissues.

The investigators have established and patented technologies using nasal immunization that induce robust mucosal immunity in animals. This pilot project will design and carry out studies that will translate the work into humans via a small clinical trial comparing and quantifying the efficacy of multimodal routes of conventional and nasal immunizations and will ultimately test the safety and efficacy of nasal immunization using a proprietary novel adjuvant technology.