Plastic and Reconstructive Surgery Residency: Resident Research

Resident Research

Congratulations to our current research resident, Dr. Raj Ambay who presented his basic science research at the University of Wisconsin Interdisciplinary Research Forum on October 26, 2006 . His poster session, entitled Evaluation of a Novel Radioiodinated Phospholipid in the Detection and Surveillance of Gliomas, was well attended and prompted exciting discussion. His position is currently funded by a T32 grant from the NIH.

We are collaborating with our colleagues in the Department of Pathology who have developed a Cultured human Skin Substitute (CSS) with enhanced vascularization properties for use in the treatment of large burn injuries and chronic wounds. Delays in vascularization of CSS's contribute to clinical failure. Our CSS is generated from a human cell line that has been genetically engineered to express proangiogenic factors such as VEGF and HIF-1 a . Structurally it has an epidermal and dermal layer, which makes it robust compared to existing CSS's made only of fragile epidermal sheets (Fig 1A). Using software we developed with our colleagues in the computer science department, we are able to quantify vascular growth in grafted specimens and provide a visual representation of the results (Fig 1B, C). Ongoing work will involve further characterization of NIKS cell lines and development of wound healing models with emphasis on vascular morphology, factors influencing angiogenesis, and wound healing physiology.

Fig 1 . These panels demonstrate (A) fully stratified H&E stained cultured skin substitute, (B) mouse skin capillaries labeled with fluorescent dye, and a (C) capillary density map of the center image

We are evaluating the capabilities of a novel tumor selective radiopharmaceutical (NM404) that may have clinical value in tumor-specific imaging and therapy. In a collaboration with the Department of Radiology and the UW Cancer Center, we have access to the world's first hybrid high resolution microPET/microCT scanner, as well as state-of-the-art histologic imaging equipment for our brain and colon cancer models. The outcome of this study may allow for a more precise cancer staging, and a better imaging method to follow progression, detect recurrence, and monitor therapy and treatment. In the near future, we hope our data in rodent models provides the impetus for extending the current human clinical trials of NM404 to patients with lethal brain and colon cancer.

Fig 1 . Fused 3D surface-rendered MRI image (blue) and 3D microPET image (A) with 124I-NM404 into a rat with a brain tumor. Right panels show (B) contrast-enhanced coronal MRI slice through the tumor (arrow) and (C) fused coronal MRI and 124I-NM404 microPET images corroborating presence and location of the tumor.

Analysis of microvasculature and cellular viability in the progression to colon cancer

In a collaborative effort with the laboratory of William F. Dove from the McArdle Cancer Research Center, we have developed a method for assessing the vasculature of the normal intestinal epithelium and its neoplastic counterpart. The vasculature of the normal intestinal epithelium is highly organized with a large vessel running through the center of each villus and a network of smaller vessels covering the surface. By contrast, the vasculature of a tumor lacks a discernible pattern with vessels of many different sizes running chaotically through the tumor. Interestingly, some regions of the tumor are unstained. We hypothesize that the microvascular architecture is valuable in the characterization of the normal intestinal epithelium, adenomas, and adenocarcinomas. Further, we believe these unstained regions increase in number through the progression to cancer. A collaborative effort between the Lahvis lab and the Department of Computer Science has produced a novel software platform to visualize and calculate in three dimensions, (1) the density of vessels per cubic millimeter of tissue and (2) the number of branch points per cubic millimeter of tissue. Further, we intend to investigate images from unstained regions of the tumor for cellular proliferation, blood flow, and apoptosis. We intend to utilize both a histological approach and microPET. We anticipate the vasculature changes as tumors progress and apoptotic cells in unstained regions devoid of blood flow or cellular proliferation. This project should provide unique insights into the dependence of tumorigenesis on neovascularization.

Fig. 1 Note a (A) highly organized vasculature with a large vessel running through the center of each villus and a network of smaller vessels covering the surface. By contrast, (B) the vasculature of a tumor lacks a discernible pattern with vessels of many different sizes (arrows) (C) running chaotically through the tumor.