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1.  Therapeutic strategies impacting cancer cell glutamine metabolism 
Future medicinal chemistry  2013;5(14):1685-1700.
The metabolic adaptations that support oncogenic growth can also render cancer cells dependent on certain nutrients. Along with the Warburg effect, increased utilization of glutamine is one of the metabolic hallmarks of the transformed state. Glutamine catabolism is positively regulated by multiple oncogenic signals, including those transmitted by the Rho family of GTPases and by c-Myc. The recent identification of mechanistically distinct inhibitors of glutaminase, which can selectively block cellular transformation, has revived interest in the possibility of targeting glutamine metabolism in cancer therapy. Here, we outline the regulation and roles of glutamine metabolism within cancer cells and discuss possible strategies for, and the consequences of, impacting these processes therapeutically.
PMCID: PMC4154374  PMID: 24047273
2.  Subject-specific Myoelectric Pattern Classification of Functional Hand Movements for Stroke Survivors 
In this study, we developed a robust subject-specific electromyography (EMG) pattern classification technique to discriminate intended manual tasks from muscle activation patterns of stroke survivors. These classifications will enable volitional control of assistive devices, thereby improving their functionality. Twenty subjects with chronic hemiparesis participated in the study. Subjects were instructed to perform six functional tasks while their muscle activation patterns were recorded by ten surface electrodes placed on the forearm and hand of the impaired limb. In order to identify intended functional tasks, a pattern classifier using linear discriminant analysis was applied to the EMG feature vectors. The classification accuracy was mainly affected by the impairment level of the subject. Mean classification accuracy was 71.3% for moderately impaired subjects (Chedoke Stage of Hand 4 and 5), and 37.9% for severely impaired subjects (Chedoke Stage of Hand 2 and 3). Most misclassification occurred between grip tasks of similar nature, for example, among pinch, key, and three-fingered grips, or between cylindrical and spherical grips. EMG signals from the intrinsic hand muscles significantly contributed to the inter-task variability of the feature vectors, as assessed by the inter-task squared Euclidean distance, thereby indicating the importance of intrinsic hand muscles in functional manual tasks. This study demonstrated the feasibility of the EMG pattern classification technique to discern the intent of stroke survivors. Future work should concentrate on the construction of a subject-specific EMG classification paradigm that carefully considers both functional and physiological impairment characteristics of each subject in the target task selection and electrode placement procedures.
PMCID: PMC4010155  PMID: 20876030
Stroke; Electromyography (EMG); Pattern classification; Hand; Functional task
3.  Rho GTPases and their roles in cancer metabolism 
Trends in molecular medicine  2012;19(2):74-82.
Recently, the small molecule 968 was found to block the Rho GTPase-dependent growth of cancer cells in cell culture and mouse xenografts, and when the target of 968 was found to be mitochondrial enzyme glutaminase (GLS1) it revealed a surprising link between Rho GTPases and mitochondrial glutamine metabolism. Signal transduction via the Rho GTPases, together with NFκB, appears to elevate mitochondrial glutaminase activity in cancer cells, thereby helping cancer cells satisfy their altered metabolic demands. Here, we review what is known about the mechanism of glutaminase activation in cancer cells, as well as compare the properties of two distinct glutaminase inhibitors, and discuss recent findings that shed new light on how glutamine metabolism might affect cancer progression.
PMCID: PMC3607349  PMID: 23219172
Rho; GTPase; signaling; glutamine; glutaminase; metabolism; cancer; Warburg
4.  Why common carrier and network neutrality principles apply to the Nationwide Health Information Network (NWHIN) 
The Office of the National Coordinator will be defining the architecture of the Nationwide Health Information Network (NWHIN) together with the proposed HealtheWay public/private partnership as a development and funding strategy. There are a number of open questions—for example, what is the best way to realize the benefits of health information exchange? How valuable are regional health information organizations in comparison with a more direct approach? What is the role of the carriers in delivering this service? The NWHIN is to exist for the public good, and thus shares many traits of the common law notion of ‘common carriage’ or ‘public calling,’ the modern term for which is network neutrality. Recent policy debates in Congress and resulting potential regulation have implications for key stakeholders within healthcare that use or provide services, and for those who exchange information. To date, there has been little policy debate or discussion about the implications of a neutral NWHIN. This paper frames the discussion for future policy debate in healthcare by providing a brief education and summary of the modern version of common carriage, of the key stakeholder positions in healthcare, and of the potential implications of the network neutrality debate within healthcare.
PMCID: PMC3912707  PMID: 23837992
Network Neutrality; Common Carriage; Interoperability; Federal Communications Commission; Health Information Exchange; Telemedicine
5.  R(h)oads to microvesicles 
Small GTPases  2012;3(4):219-224.
A novel form of cell-to-cell communication involving the formation and shedding of large vesicular structures, called microvesicles (MVs), from the surfaces of highly aggressive forms of human cancer cells has been attracting increasing amounts of attention. This is in large part due to the fact that MVs contain a variety of cargo that is not typically thought to be released from cells including cell-surface receptor tyrosine kinases, cytosolic and nuclear signaling proteins and RNA transcripts. MVs, by sharing their contents with other cells, can greatly impact cancer progression by increasing primary tumor growth,1–3 as well as by promoting the development of the pre-metastatic niche.4 We have recently shown that the small GTPase RhoA is critical for MV biogenesis in human cancer cells. Moreover, we have now obtained evidence that implicates the highly related small GTPases, Rac and Cdc42, in regulating the loading of specific cargo into MVs, as well as in the shedding of MVs from cancer cells. Thus, linking the Rho family of small GTPases to MV biogenesis has begun to shed some light on a new and unexpected way that these signaling proteins contribute to human cancer progression.
PMCID: PMC3520885  PMID: 22906997
microvesicles; oncosomes; cancer; cell communication; tissue transglutaminase; glutaminase; Rho; GTPase; Warburg effect; transformation
6.  Asthma Friendly Pharmacies: A Model to Improve Communication and Collaboration among Pharmacists, Patients, and Healthcare Providers 
Pharmacists, with expertise in optimizing drug therapy outcomes, are valuable components of the healthcare team and are becoming increasingly involved in public health efforts. Pharmacists and pharmacy technicians in diverse community pharmacy settings can implement a variety of asthma interventions when they are brief, supported by appropriate tools, and integrated into the workflow. The Asthma Friendly Pharmacy (AFP) model addresses the challenges of providing patient-focused care in a community pharmacy setting by offering education to pharmacists and pharmacy technicians on asthma-related pharmaceutical care services, such as identifying or resolving medication-related problems; educating patients about asthma and medication-related concepts; improving communication and strengthening relationships between pharmacists, patients, and other healthcare providers; and establishing higher expectations for the pharmacist’s role in patient care and public health efforts. This article describes the feasibility of the model in an urban community pharmacy setting and documents the interventions and communication activities promoted through the AFP model.
PMCID: PMC3042067  PMID: 21337057
Asthma; Community pharmacy; Pharmacists; Pharmaceutical care; Collaboration; Communication
7.  Targeting mitochondrial glutaminase activity inhibits oncogenic transformation 
Cancer cell  2010;18(3):207-219.
Rho GTPases impact a number of activities important for oncogenesis. Here we describe a small molecule inhibitor which blocks oncogenic transformation induced by various Rho GTPases in fibroblasts, and the growth of human breast cancer and B lymphoma cells, without affecting normal cells. We identify the target of this inhibitor to be the metabolic enzyme glutaminase, which catalyzes the hydrolysis of glutamine to glutamate. We show that transformed fibroblasts and breast cancer cells exhibit elevated glutaminase activity that is dependent on Rho GTPases and NFκB activity, and is blocked by the small molecule inhibitor. These findings highlight a previously unappreciated connection between Rho GTPase activation and cellular metabolism, and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.
PMCID: PMC3078749  PMID: 20832749
8.  The molecular basis for the regulation of the CBC by the importins 
The binding of capped RNAs to the cap-binding complex (CBC) in the nucleus, and their dissociation from the CBC in the cytosol, represent essential steps in RNA-processing. Here we show how the nucleocytoplasmic transport proteins, importin-α and importin-β, play key roles in regulating these events. As a first step toward understanding the molecular basis for this regulation, we determined a 2.2 Å resolution x-ray structure for a CBC-importin-α complex that provides a detailed picture for how importin-α binds to the CBP80 subunit of the CBC. Through a combination of biochemical studies, x-ray crystallographic information, and small-angle scattering experiments, we then determined how importin-β binds to the CBC through its CBP20 subunit. Together, these studies enable us to propose a model describing how importin-β stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export.
PMCID: PMC2782468  PMID: 19668212
9.  Unloading RNAs in the cytoplasm 
Nucleus  2009;1(2):139-143.
The nuclear cap-binding complex (CBC), a heterodimer comprised of a 20 kDa subunit (CBP20) and an 80 kDa regulatory subunit (CBP80), binds to nascent RNA polymerase II transcripts and is important throughout different aspects of RNA metabolism. In a recent publication, using a combination of X-ray crystallographic information, mutagenesis studies, small-angle scattering experiments, analytical ultracentrifugation and in vivo assays, we presented evidence that importin-α and importin-β, two nucleocytoplasmic transport proteins, play key roles in regulating the binding of capped RNA by the CBC in cells. A model for how complexes between CBC and the importins cycle in and out of the nucleus and direct the proper positional binding and release of capped RNA is presented here and is discussed in light of recent publications.
PMCID: PMC3030688  PMID: 21326945
cap binding protein; capped mRNA; capped U snRNA; importin-α; importin-β; CBC regulation

Results 1-9 (9)