“Selective In Vivo Cell Labeling Mediated Cancer Targeting”
Kaimin Cai, 2016 Beckman Graduate Fellow, Bioimaging Science and Technology Group
Distinguishing cell-surface receptors between cancer and normal cells is vital for preferential cancer diagnosis and targeted treatment. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto cell surface. However, cancer-selective labeling remains a great challenge. Herein we report the design of sugar precursors that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond, which can be cleaved in response to cancer-specific triggers and thus enables the expression of azido groups on the surface of target cancer cells. Histone deacetylase/cathepsin L-responsive acetylated azidomannose (DCL-AAM), one such trigger-activatable Ac3ManAz derivative developed, mediated excellent cancer-specific labeling in vivo, which enhanced tumor accumulation of dibenzocyclooctyne-doxorubicin conjugate via Click chemistry and consequently exerted robust anticancer activities against a series of mice tumor models.
“Novel Roles of Striatal Enriched Protein Phosphatase (STEP) in Homeostatic Plasticity and Epileptic Seizure”
Sung-Soo Jang, Ph.D. candidate, Cellular and Molecular Foundations of Intelligent Behavior Group
Striatal enriched protein phosphatase (STEP) is a brain specific tyrosine phosphatase, which is crucial for activity-dependent synaptic alterations such as Hebbian forms of synaptic plasticity at excitatory synapses in the brain. Homeostatic synaptic plasticity maintains synaptic strength and flexibility within physiological limit in response to sustained changes in neuronal activity. We demonstrated a bidirectional modulation of STEP61 level and activity by prolonged alterations of hippocampal network activity and an involvement of STEP61 in synaptic up-scaling under dampened neuronal activity.
Electroconvulsive seizure (ECS) induces generalized tonic-clonic seizures with low mortality and is widely used to screen anti-epileptic drugs. We showed that a single episode of ECS, but not consecutive ECS for seven days increases protein expression of membrane-associated STEP61 in the hippocampal membrane fractions at 48 h following a single epileptic event.
Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures caused by recurrent and synchronized electrical discharge within the brain. We found that status-epilepticus (SE) increases the protein expression of STEP and STEP KO mice where STEP gene is absent display reduced seizure propensity, which might be related to an increase of HCN channels conductance and intrinsic excitability in hippocampal CA2 neurons.
“Multiscale Methods for Confined Fluid Transport”
Ravi Bhadauria, Ph.D. candidate, Computational Multiscale Nanosystems Group
The study of fluid transport process and its mechanism at nanometer scales is important due to its implications in a variety of processes such as gas separation, heterogeneous catalysis, carbon sequestration, water purification, and understanding biological flows in membranes. In this talk, I would discuss the development of high fidelity computational multiscale methods to understand confined fluid flow past solid interfaces. Because of the dominant surface effects at the nanoscale, the classical, field-based continuum models break down. Material properties such as density, viscosity, diffusion coefficient etc. can no longer be assumed constant. Particle-based methods (i.e., molecular dynamics) offer accurate insights into the flow physics but are computationally expensive. In addition, the ratio of pertinent to total information (particle trajectories) from these simulations is very small. Our multiscale framework overcomes the challenge of bridging these two descriptions of the flow physics at disparate length and time scales to a unified, field based quasi-continuum framework that provides atomistic level resolution with continuum level computational efficiency. Further, the proposed method is successively refined to make it viable for a variety of flow situations, such as Couette flow and gravity-driven flows of single- and multicomponent fluids, as well as electro-hydrodynamics. Our adsorption based understanding of the flow physics elucidates that the “slip-length” does not change with the pore width as previously conjectured.