2011 Funded Pilot Projects
Elliott Botvinick, PhD
Bloodless Laparoscopic Cutting Tool
In urology, laparoscopic partial nephrectomy has become an increasingly effectivesurgical technique for the removal of benign and malignant lesions, while preservingrenal function. Because the kidney is a well-vascularized organ, there is significantbleeding involved with cutting. In order to maintain visualization throughout the cutting ofthe kidney, urologists have devised a means of preventing blood flow to the renalparenchyma by clamping the main renal vessels. Since clamping the renal vessels maycause renal ischemia and subsequent permanent renal damage to the entire organ,there is a need for a surgical tool that can bloodlessly resect highly vascularized tissuewithout the need for clamping. Such a tool will significantly lower risk to the patient aswell as lower the skill threshold required to safely perform resection of any highlyvascularized tissue. We propose to combine laser photocoagulation with laser ablationso that vessel coagulation occurs just prior to ablation, thus precluding bleeding. We willfurther seek optimal pulse duration, beam focus and operating wavelength to achieveablation without significant carbonization or smoke. We will seek SBIR and privatefunding to move the project through clinical trials and to commercialize it in internationalmarkets.
Elizabeth Chao, MD
Early Detection of Prostate Cancer by Profiling Nucleosome Phase Profiling in Peripheral Samples
The promise of using peripheral samples, such as blood, urine, or sputum as a simple non-invasive way to diagnose cancer or screen for residual disease has remained relatively unfulfilled. Challenges include low and variable numbers of tumor cells, and substantial degradation. However, it has been reported that DNA protected within the nucleosome can be reliably detected in these samples. An assay that relies on this unit of DNA would be more robust than assays for nucleic acids from internucleosomal regions. It is well established that default nucleosome localization in humans is based on cis DNA sequences. Depending on the cell type, nucleosomes may either be absent or shifted in position on the DNA. It is possible to recognize a cell type, including malignancy, from this phasing. The phasing of nucleosomes has not previously been used to improve cancer detection.To submit a strong application for extramural funding, we are in critical need of preliminary data demonstrating our ability to robustly identify nucleosomal phasing shifts in peripheral samples. With this data and the substantial resources available to us through the UCI-SPECS program, our genomics team will be imminently poised to apply these methods towards improvements in prostate cancer detection and surveillance.
Gregory Evans, RD, MD, FACS
Reprogramming of Adipose Derived Stem Cells (ADSCs) to iPS And Further Differentiation to Neuronal Cells for the Treatment of Peripheral Neuropathy
Damage to peripheral nerves is considerably more common and the cost to the labor force and worker compensation system is staggering. Despite the intrinsic capacity of the peripheral nervous system to regenerate as well as advances in neurobiology, pathophysiology, intra- and post -operative management and microsurgery, functional recovery and clinical outcomes after peripheral nerve injuries are still poor. Nerve autografting is not a good option due to a secondary injury and morbidity in the donor site.Pluripotent stem cells are a great source of varying cell types that are used for tissue regeneration or repair of damaged tissue. For practical purpose, use of hES cells have faced difficulties because of ethical issues and potential immuno-incompatibility. The establishment of iPS cells both from mouse and human adult tissue by 4 reprogramming factors has raised hope for alternative potential to ES cells. In our lab, hADSCs are isolated for reprogramming to iPS by using 4 reprogramming factors delivered by minicircle. ADSC is the most abundant in fat tissue, easy to collect autologously making it an attractive source for adult stem cells. We are proposing for the ICTS award for continuing our research for the generation of iPS and further differentiation to neuronal cells.
Leslie Flanagan, PhD
Developing a Novel Cell Sorting Technology to Purify Cells For Transplantation
Development of a label-free method for purifying stem cells prior to transplantation wouldremove a significant roadblock for the use of stem cells as therapies for human diseaseand injury. Generation of homogeneous populations of cells for transplantation will helpdefine the precise contributions of specific cell types to repair and remove unwantedtumorigenic cells prior to transplantation. Through an interdisciplinary collaboration withengineering colleagues, we have analyzed neural lineage cells using a label-freetechnique termed “dielectrophoresis”, or DEP, that can be used to separate cells withdistinct characteristics. Our data show that DEP distinguishes neural stem cells frommore differentiated progeny and dielectric properties consistently reflect fate potentialacross multiple sets of neural stem/progenitor cells (NSPCs) and over time in culture.Exposing mouse and human NSPCs to DEP forces necessary for cell separation did notalter survival, proliferation, or differentiation, establishing DEP as a reasonable methodfor separating these cells. Furthermore, high frequency DEP can be used to isolateNSPCs biased to make neurons, confirming that DEP-based sorting can separateNSPCs with specific fate potential. We hypothesize DEP will be a critical alternative andpotential complement to FACS for purification of cells for transplantation and willcompare these sorting methods.
Arash Kheradvar, PhD
Development of a Novel Self-expandable Bioprosthetic Heart Valve for Percutaneous Delivery and Implantation
Percutaneous replacement of heart valves has appeared as a potential therapy to reduce thenumber of reoperations in young patients with congenital heart defects and to avoid open heartsurgery in severely ill patients. Yet, a considerable number of patients are not ready forpercutaneous procedures due to the current limitations of the valve delivery size. This projectaims to develop a novel percutaneous heart valve system implantable in aortic/pulmonary valveposition whose delivery size is about 12 French-catheter.
The following specific aims will beaddressed within the duration of this award:
Aim 1: To manufacture the valve prototype from shape-memory Nitinol and bovine pericardium.
Aim 2: To test the functionality of the valve system in vitro in a heart flow simulator with the aidof high-speed imaging.
This project is translational due to its impact on percutaneous replacement of heart valves. The extremely small delivery-size would result in ease of implantation procedure by either a cardiacsurgeon or an interventional cardiologist. Upon completion of the procedure, the patient wouldexperience a shorter recovery period while the cost of the procedure is much less than atraditional cardiac surgery. This technology is amenable to both adult and pediatric age groups.
Dara Sorkin, PhD
Unidas Por La Vida: United For Life
The NIH has funded a pilot project designed to test the effectivenessof a family-based intervention program to promote physical activity and weight loss among Mexican-Americanmother-daughter dyads (mothers have type 2 diabetes; daughters are overweight or obese, with pre-diabetes).We are proposing to leverage the current study to collect additional data on mothers’ and daughters’ circulatinglevels of stress hormones and inflammatory markers. This aim was not included in the funded grant. TheUnidas intervention is novel in its use of community health workers to reach women in their homes andcommunities to provide culturally-tailored support for behavior change. This randomized, controlledintervention trial is conducted in the real-world setting where Mexican-American women struggle with socialculturalbarriers to engaging in exercise, losing weight, and managing stress, and utilizes resources thatalready exist in their own community to achieve a healthy lifestyle. The proposed ICTS pilot study will explorethe longitudinal relationship between stress and weight loss in the context of a treatment trial and will providedata on circulating levels of stress hormones and inflammatory markers in obese Latinas, which will greatlystrengthened our future R01 proposal.