BME students awarded at 2014 Denman Undergraduate Research Forum

Biomedical Engineering seniors Bridget Crawford, Ryan Reyes and Michael Whipple received recognition for their work at the 19^th Denman Undergraduate Research Forum. The annual event provides undergraduate students at Ohio State with “an opportunity to showcase outstanding student research, scholarship, and creative activity and encourage all undergraduates to participate in these activities to enrich their undergraduate education.”

Congratulations to Bridget, Ryan and Michael on their tremendous success!

Below is a description of Bridget Crawford’s research conducted in BME Associate Professor Stephen Lee’s lab. Bridget received 3^rd place in the Engineering category.

Immunologically Modified FETs for Protein Detection in Biological Fluids

Field effect transistors (FETs) are solid-state electrical devices with semiconductor channels through which charge carriers migrate and generate current. The application of an electric field proximal to the conductive channel causes a change in current depending on the sign and magnitude of the field. FETs can be modified for protein sensing by deployment of antibodies as receptors on the channel surface to create an immunologically modified FET (immunoFET). Binding of analytes brings a layer of charge proximal to the channel surface, causing modulation of current that is easily detectable, allowing for quantitative detection of unlabeled analytes. We present the successful detection of  inflammatory chemokine CXCL9 in both murine serum and human urine from transplant patients using immunoFETs modified with anti-CXCL9 IgG. CXCL9 was detected in renal transplant urine at biologically relevant levels and correlated with rejection by renal biopsy. The presented work demonstrates the feasibility of immunoFET sensor operation in physiologic buffers, and shows the potential to provide real-time quantification and monitoring of inflammatory mediators, allowing for minimally invasive interrogation of graft status. The FET design may be scalable to allow for real-time, label-free, point-of-care diagnostic use.

Below is a description of Ryan Reyes’ research conducted alongside Dr. Samson Jacob, Professor of Cancer Research, Molecular & Cellular Biochemistry, and Medicine. Ryan received 1^st place in the Health Sciences-Laboratory/Cellular category.

miR-23a: A Key Metabolic Regulator in Hepatocellular Carcinoma

Liver cancer is the fifth most common type of cancer in men and the seventh most common in women. However, due to late diagnosis and lack of effective drugs, liver cancer is the second most frequent cause of death from cancer in men.  Our laboratory aims to explore alternate strategies for treatment of liver cancer.  We have shown that a naturally occurring molecule, miR-23a, is capable of changing the  way energy is produced in liver cancer.  My project aims to further our understanding of how miR-23a can alter energy production.  A better understanding of this process should facilitate development of new anticancer therapeutics by taking advantage of the altered energy metabolism in liver cancer.

Below is a description of Michael Whipple’s research that won 2^nd place in the Health Sciences- Laboratory/Cellular category. Michael, who is advised by BME Associate Professor Dr. Thomas Hund, also took 3^rd place for the research at the Undergraduate Research Forum for the College of Engineering and Architecture.

Ca²⁺/Calmodulin-Dependent Protein Kinase II-Dependent Regulation of TREK-1

Ion channels serve as core constituents of macromolecular complexes that regulate cell membrane excitability.  Importantly, ion channel activity is heavily regulated by posttranslational modifications (e.g. phosphorylation, oxidation).  In previous studies, we have identified a role for the actin-associated polypeptide, β_IV-spectrin in localization and phosphorylation of ion channels through multifunctional serine/threonine kinase Ca²⁺/calmodulin-dependent kinase II (CaMKII).  Furthermore, we have identified TREK-1, a mechano-sensitive two-pore domain K⁺ channel, as a novel member of this spectrin-based signaling complex in cardiomyocytes. Posttranslational modification of TREK-1 has been implicated in control of cell excitability and cytoskeletal organization.  However, little is known about the mechanism and/or role of CaMKII-dependent regulation of TREK-1. The specific goal of this project was to determine the molecular mechanism(s) for CaMKII-dependent regulation of TREK-1 activity. Our studies indicate that CaMKII phosphorylates TREK-1 at a site in the N-terminal intracellular domain.  Furthermore, we demonstrate that a potential CaMKII phosphorylation site in the TREK-1 N-terminus may regulate cell size and morphology.  Together, our findings provide insight into a new molecular pathway for regulation of TREK-1 activity and cell structure.  We anticipate that this TREK-1-dependent pathway will be important in the setting of cardiac hypertrophy and heart failure