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A GEM of a Prize

July 18, 2014 By Patti Wieser, UC San Diego

Research image related to the Wang-Xu GEM project: Shown are the conformational activation of a biosensor molecule based on fluorescence resonance energy transfer (FRET) and the FRET ratio images of cells expressing the biosensor. EGF is epidermal growth factor. The dark blue strands (with little blue ovals) in the -EGF are the image of two cells before EGF stimulation while the red strands with green ovals in the +EGF are those after EGF stimulation. The yellow, blue and pink basket-like clumps in the left top are the cartoon representations of the FRET biosensor molecule before and after activation.Two physician-engineer teams from UC San Diego have been selected as the 2014 recipients of the Galvanizing Engineering in Medicine (GEM) awards from the Clinical and Translational Research Institute (CTRI) and the Institute of Engineering in Medicine (IEM). GEM, an initiative of UC San Diego’s CTRI and IEM, supports projects that identify clinical challenges for which engineering solutions can be developed and implemented to improve health care. 

The GEM awardees are Douglas Conrad, MD, and Drew Hall, PhD, who are collaborating on an at-home monitoring device for cystic fibrosis (CF) patients, and Yingxiao Wang, Ph.D., and Xiangdong Xu, MD, PhD, who are collaborating on molecular engineering and imaging of T cells for immunotherapy of multiple myeloma. Each team is receiving $60,000 for their research projects.

“We are very pleased to announce this year’s GEM awards,” said Gary S. Firestein, MD, Director of CTRI. “These two projects are outstanding examples of bridging UC San Diego’s strengths in clinical care and engineering to develop innovative healthcare solutions, and show great promise for helping cystic fibrosis and multiple myeloma patients. They also reflect how CTRI’s funding by the NIH National Center for Advancing Translational Sciences leverages resources and meaningful collaborations.”

Conrad and Hall are developing a smartphone-based biosensor to monitor pH and pulmonary exacerbation biomarkers in patients with CF, an inherited chronic disease that affects the lungs and digestive system of about 30,000 children and adults in the U.S. Exacerbations – CF flare-ups characterized by infection, increased coughing and sputum, and lessened lung function – decrease the quality of life for CF patients and can irreversibly damage airways. The Conrad-Hall biosensor could enable close monitoring of pH levels and biomarkers, speeding up medical interventions for treating airway infections and preventing permanent damage. 

“It is our hypothesis that a common smartphone can be transformed into a low-cost, point-of-care medical tool for an at-home monitoring of CF exacerbations and provide physicians with long-term actionable data to adjust therapy,” said Conrad and Hall in their GEM proposal.  

Conrad is a professor of medicine and director of the Adult Cystic Fibrosis Clinic at UC San Diego. Hall is an assistant professor in electrical and computer engineering at UC San Diego’s Jacobs School of Engineering and leads the multidisciplinary BioSensors and BioElectronics research group. Hall is also the recipient of an innovative technology pilot project award from CTRI this year to develop smart-phone technology for detecting HIV-associated tuberculosis in patients who live in remote settings. He is a member of the Center for Wearable Sensors at the Jacobs School of Engineering.

Wang and Xu are developing molecular biosensors and machineries for the engineering and imaging of T cell activities for immunotherapy for multiple myeloma. Multiple myeloma is a blood cancer that begins in plasma cells and usually results in dysfunction of the bone marrow.

A promising approach for cancer immunotherapy is the transfer of artificial T cell receptors. “This therapeutic strategy is based on the genetic reprogramming of T cells with a synthetic immune receptor that directs them against malignant cells and enables target destruction,” explained Wang and Xu. They noted that T cells with single artificial receptors, also called chimeric antigen receptors or CARs, have demonstrated promising therapeutic effects in several clinical trials of immunotherapy against leukemias and blood diseases. The Wang-Xu team’s fluorescence resonance energy transfer (FRET) biosensors and imaging have been successful in quantifying various molecular events in live cells with high specificity and sensitivity.

Wang is an associate professor in bioengineering and IEM at UC San Diego specializing in molecular engineering, FRET, live cell imaging, and bio-nanotechnology. Xu is an assistant professor of pathology at UC San Diego and VA San Diego Healthcare System and an expert in hematopoietic malignancies and multiple myeloma.

“GEM is a ground-breaking program. We expect that it will have significant impact on healthcare at UC San Diego and set a precedent for establishing multidisciplinary teams to solve other unmet clinical challenges,” said Deborah Spector, PhD, Chair of the GEM Committee and Director of CTRI Translational Research Alliance.

The GEM Committee includes: Gary S. Firestein, MD, CTRI Director; Deborah Spector, PhD, GEM Committee Chair; Shu Chien, MD, PhD, IEM Director; Teri Melese, PhD, Industry Research Alliances Assistant Vice Chancellor; Sharon Franks, PhD, Research Proposal Development Service Director; and Priya Bisarya, bioengineering student.

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