Cystic Fibrosis
We have several ongoing CF projects involving Drs. Accurso, Hunsucker and Duncan. Some of these studies have been funded by the Cystic Fibrosis Foundation through grants to Dr. Duncan and more recently, Dr. Hunsucker. Studies are focused on the discovery and validation of biomarkers for cystic fibrosis and our primary objective is to move the biomarkers we discover into routine clinical use. Examples of other CF projects underway include the application of multiplexed cytokine assays (arrays) to studies of serum samples obtained from CF subjects.
Lung Cancer
Our lung cancer studies involve collaboration between Italy, Japan, Australia and several sites in the USA. We are developing and evaluating approaches based on mass spectrometry that can distinguish between those lung cancer subjects that are responsive and those that are unresponsive to gefitinib treatment. Key to the success of this collaboration is the application of novel software being developed by Biodesix of Steamboat Springs. Drs. Solomon (now back in Australia) and Hunsucker are also employing DIGE to characterize the proteins that distinguish between distinct cell lines with differential responsiveness to gefitinib.
Infectious Diseases
In collaboration with Drs. Brian Ward and Momar Ndao (McGill University) we aim to identify and characterize novel biomarkers of infectious diseases prevalent in the developing world. We also propose to develop high-throughput, cost effective assays for each promising biomarker. Early work has focused on bebesia and schistosomiasis, while future work will address other more prevalent diseases including malaria.
Peanut Allergens
In collaboration with Dr. Steven Dreskin (Immunology, UCDHSC) we are applying proteomics to identify and quantify peanut allergens. By combining functional assays with standard immunoblotting techniques & proteomics we hope to be able to identify the peanut allergens quantitatively responsible for mast cell activation in patients with systemic reactions to peanuts.
Alzheimer's Disease
In collaboration with Dr. Ros Krajcik (Orentreich Foundation) we are employing novel proteomic methods to identify biomarkers of Alzheimer's disease in a large and carefully characterized patient population.
Breast Cancer
Lindsay Weitzel, in collaboration with Drs. Anthony Elias (UCDHSC) & Nancy Kiviat (University of Washington), is employing proteomic methods to identify biomarkers of breast cancer.
Down Syndrome
In collaboration with Dr. David Patterson (Eleanor Roosevelt Institute, University of Denver) we are assessing the protein expression levels in specific brain regions of an animal model of DS (Ts65Dn mice). This work employs two dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. In our initial studies we have identified some of the temporal post-mortem changes in brain proteins.
Studies of the Tear Film
In collaboration with Drs. Durairaj and Kahook (Ophthalmology, UCDHSC) we are exploring the diagnostic potential of human tear fluid. In earlier work we identified over 500 unique peptides and proteins in human tear fluid. We are examining the protein expression profile of tear film in several ophthalmic disorders including diabetic retinopathy and macular degeneration.
Diabetes and Islet Transplants
In collaboration with Dr. Mark Nicolls (UCDHSC) we are establishing a panel of biomarkers that assess human islet viability for successful transplantation. Our preliminary data indicate that biomarkers in pre-transplanted islets can distinguish between high grade (i.e., those suitable for transplantation) and low-grade islets.
Pulmonary Hypertension
In collaborator with Drs. D. Dunbar Ivy (The Children's Hospital, Denver) we aim to gain a better understanding of the underlying events in pulmonary hypertension. We are examining the differences arising from novel treatments of pulmonary arterial hypertension (e.g., bosentan, sildenafil, sitaxsentan, ambrisentan, treprostinil, epoprostenol and iloprost) and employing animal models to better characterize the biochemical changes associated with this condition.
Thyroid Cancer
Thyroid cancer is the most common endocrine malignancy with the most common clinical presentation being a thyroid nodule. Biomarker discovery studies in our laboratory have compared different thyroid malignancies with normal tissue in order to compare the relative abundances of individual proteins. We have identified potential biomarkers and are now establishing high-throughput, sensitive, cost effective assays based on well accepted clinical laboratory methods to establish their clinical utility. We aim to develop a clinical assay that provides sufficient diagnostic power to correctly distinguish malignant from benign thyroid nodules.
Biliary Atresia
In collaboration with Dr. Ronald J. Sokol we are employing two dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry to compare proteomes of patients with biliary atresia and patients with total parenteral nutrition-related chloestasis for biomarker discovery.
