Dreidink Scholars Program
Philanthropic generosity of the Dreidink family has allowed the Center for Translational to form the Dreidink Scholars Program, founded in 2015. The Dreidink Scholars Program supports summer research undertaken by first year medical students at TJU during the summer that concludes first year medical school. From among those students participating, one student is chosen each year to receive the Dreidink Scholar award, based on the student’s: 1) accomplishments in the lab; and 2) potential for a successful career in translational research.
Timothy Brandt, Class of 2018
Timothy Brandt, working in the lab of Dr. Tung Chan, helped develop a novel quantitative assay to test whether recently discovered drugs could be used to treat insulin resistance. Resistance to insulin, a hallmark condition in Type 2 diabetes, is typically measured by assessing (reduced) GLUT4 enzyme-mediated glucose uptake in cells. Dr. Chan’s laboratory discovered novels drugs that directly activate the Akt kinase, a key glucose uptake regulator. Tim developed a quantitative assay that uses infrared-on-cell imaging technology and muscle cells in multi-well plates to detect GLUT4 that is exposed to the outer cell membrane. The assay automatically measures signals from thousands of cells and from up to 96 wells at the same time. In contrast, the current standard method requires the assessment of each cell under a microscope magnification, in which accurate quantification is challenging due to photo bleaching, low throughput and observation bias. Tim’s efforts developing a high throughput system for screening drugs regulating glucose uptake are helping pave the way to new diabetes treatments.
Taylor Karl, Class of 2019
Taylor Karl, working in the lab of Dr. Deepak Deshpande, investigated molecular mechanisms of bitter taste receptor (TAS2R) -mediated relaxation of airway smooth muscle cells. Recent studies in human cell and mice have demonstrated that TAS2R agonists are expressed on airway smooth muscle (thus not just on the tongue1), and when activated can dilate airways to improve airflow under conditions of an asthmatic attack. Therefore, TAS2Rs have emerged as promising potential therapeutic targets in the treatment of asthma. Establishing molecular mechanisms by which TAS2R agonists relax airway smooth muscle is a first critical step in exploiting bitter tastants as potential anti-asthma drugs. Taylor investigated the role of actin cytoskeletal reorganization as a potential means by which TAS2Rs cause airway smooth muscle relaxation. In addition, Taylor studied the role of gustducin, a well-known Gi family G protein that is known to mediate TAS2R signaling in taste bud cells. Findings from Taylor’s studies demonstrated that TAS2R-mediated signaling in airway smooth muscle is partly mediated via gustducin. Future studies are needed to ascertain the contribution of additional G proteins in TAS2R signaling in airway smooth muscle cells, and how the novel mechanisms by which TAS2Rs can be exploited therapetically.
Brenda French, Class of 2020
Brenda French, working in the lab of Dr. Sophie Astrof, employed CRISPR technology to knock-in green fluorescent protein (GFP) or other fluorescent proteins at the end of the fibronectin gene, in order to be able to visualize fibronectin in cells throughout embryonic development. Fibronectin is an extracellular matrix protein that functions by binding the surface of cells to help regulate cell adhesion, growth, migration, and differentiation during embryonic as well as post-natal development. Brenda also generated targeting constructs containing GFP, mScarlet, mCardinal, or DENDRA2 as well as guideRNA-containing constructs, and used these plasmids to establish stable primary cell lines such as embryonic fibroblast and cardiac endothelial cells, each expressing fibronectin-fluorescent protein fusions of a different color. Brenda also generated targeting and guideRNA constructs to generate integrin a5-fluorescent protein fusions in animal models. Collectively, her efforts have helped generate novel tools for assessing how interactions between the matrix and cells guide the development of tissues such as the branches of the aorta; understanding these processes is key to preventing development abnormalities that can arise in the vascular system of newborns.
Nathaniel Ash, Class of 2021
Nathaniel Ash, working in the lab of Dr. Shey-Shing Sheu, participated in the phenotypic characterization of cardiac arrhythmias in various genetically modified mouse models. It is known that the most robust Ca2+ uptake in cardiac mitochondria is through mitochondrial Ca2+ uniporter (MCU). However, Dr. Sheu’s laboratory has pioneered the concept that there are additional Ca2+-influx mechanisms including mitochondrial type 1 ryanodine receptor (mRyR1) despite the commonly held belief that MCU is the sole mitochondrial Ca2+-influx mechanism. The discovery that genetic knockout (KO) of MCU in adult mouse hearts leads to minimal adverse phenotypes prompted additional interest into the physiological role of mRyR1 in Ca2+-influx. Nathaniel categorized the phenotypes of inducible cardiac specific MCU KO, mRyR1 KO, and MCU/mRyR1 double KO mice. Additionally, Nathaniel helped to quantify the KO efficiency in the mouse populations used in the study. His experimental results showed that mRyR1 KO and MCU/mRyR1 double KO mice are more susceptible to cardiac arrhythmias and sudden cardiac death. His research helped establish cardiac phenotypes of these mouse models that support the physiological and pathological significance of mRyR1 in the heart. Further studies need to be conducted to elucidate the molecular mechanisms that underlie the observed phenotypes.