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Texas Tech University Health Sciences Center

www.ttuhsc.edu
Fifth Street, TX, United States

The Texas Tech University Health science Center offers programs in Allied Health science, Biomedical science, Medicine, Nursing, and Pharmacy. TTUHSC's main campus is in Lubbock, but campuses are also located in Abilene, Amarillo, Dallas, El Paso and the Permian Basin. TTUHSC serves more than 100 counties in the western portion of Texas. The university is a separate but equal institution from Texas Tech University, and both universities are part of the Texas Tech University System. Wikipedia.

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SOLANA BEACH, Calif., May 10, 2017 (GLOBE NEWSWIRE) -- Evoke Pharma, Inc. (NASDAQ:EVOK), a specialty pharmaceutical company focused on treatments for gastrointestinal (GI) diseases, today announced that data from its Phase 3 trial of Gimoti™, its patented nasal delivery of metoclopramide for the relief of symptoms associated with acute and recurrent diabetic gastroparesis in women, were presented at the Digestive Disease Week® (DDW) 2017 Meeting held in Chicago, Illinois. The poster presentation entitled “Symptom Severity Influences Drug Efficacy in Women with Diabetic Gastroparesis: Results of a Phase 3 Study with Metoclopramide Nasal Spray” illustrated that patients with moderate to severe symptoms at study entry, which included 105 of the 205 patients (51%) enrolled in the study, responded clinically and statistically significantly better to Gimoti than placebo at multiple time points in the Intent-to-Treat (ITT) and Per Protocol populations. Focusing on the benefits in patients with moderate to severe symptoms is consistent with the U.S. Food and Drug Administration (FDA) guidance on the clinical evaluation of drugs for the treatment of gastroparesis issued in July 2015 (Gastroparesis: Clinical Evaluation of Drugs for Treatment, Draft Guidance). In the Phase 3 trial, Gimoti was particularly effective in reducing nausea and upper abdominal pain, the most common and debilitating symptoms in patients with moderate to severe symptoms. This was similar to the benefits experienced by female patients in the Company’s Phase 2b trial. Safety data from the Phase 3 trial were consistent with favorable results from previous Gimoti studies. In particular, there were no adverse events of special interest, such as the central nervous system (CNS) effects observed with oral and parenteral formulations of metoclopramide. Based on recent FDA discussions, these data are anticipated to be submitted as part of a new drug application (NDA) for Gimoti. “As we prepare our 505(b)(2) NDA for Gimoti, including a comparative exposure pharmacokinetic (PK) study, acceptance of our Phase 3 data as a late breaker for poster presentation at DDW 2017 provided another opportunity for us to share the clinical importance of metoclopramide nasal spray for women suffering from the symptoms of moderate to severe diabetic gastroparesis,” stated Marilyn R. Carlson, DMD, MD, Chief Medical Officer. “We are very pleased that DDW accepted this data for presentation as we believe it is among the most up-to‑the-minute and novel GI developments that will impact research and the care of patients.” The Phase 3 trial was a U.S. multicenter, randomized, double-blind, placebo-controlled, parallel‑group study of the efficacy and safety of Gimoti compared to placebo in adult female subjects with symptomatic diabetic gastroparesis and delayed gastric emptying. Eligible patients were randomized 1:1 between Gimoti or placebo administered as a single nasal spray four times daily; 30 minutes before meals and at bedtime for a total of four weeks. The primary endpoint was the change in the total symptom score from baseline to week four. The trial data was not statistically significant in the ITT group (N=205, p=0.881). The authors of the presentation were Richard W. McCallum, MD, Texas Tech University Health Sciences Center, El Paso, Texas; Ronnie Fass, MD, Case Western Reserve University, Cleveland, Ohio; Bal R. Bhandari, MD, Delta Research Partners, Monroe, Louisiana; Marilyn R. Carlson, DMD, MD and Wayne M. Alves, PhD, Evoke Pharma, Inc., Solana Beach, California. The data poster is available on the investors section of the Company’s website, http://investor.evokepharma.com/, under the “Presentations and Posters” section. Evoke is a specialty pharmaceutical company focused primarily on the development of drugs to treat GI disorders and diseases. The Company is developing Gimoti, a metoclopramide nasal spray for the relief of symptoms associated with acute and recurrent gastroparesis in women with diabetes mellitus. Diabetic gastroparesis is a GI disorder afflicting millions of sufferers worldwide, in which the stomach takes too long to empty its contents resulting in serious digestive system symptoms. Metoclopramide is the only product currently approved in the United States to treat gastroparesis, and is currently available only in oral and intravenous forms. Gimoti is a novel formulation of this drug, designed to provide systemic delivery of metoclopramide through nasal administration. Visit www.EvokePharma.com for more information. Evoke cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negatives of these terms or other similar expressions. These statements are based on the company's current beliefs and expectations. These forward-looking statements include statements regarding: Evoke’s plans to present at DDW and discuss the data from its Phase 3 trial for Gimoti; the benefits Gimoti may have for patients with moderate to severe gastroparesis symptoms; the timing of any 505(b) (2) NDA submission for Gimoti with the FDA; the Company’s plans to conduct the comparative exposure PK study and include the results in the Gimoti NDA; and the utility of the Gimoti data to scientists and clinicians at DDW. The inclusion of forward-looking statements should not be regarded as a representation by Evoke that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Evoke's business, including, without limitation: risks associated with successfully commencing and receiving favorable results from the planned PK trial; later developments with the FDA that may be inconsistent with the already completed pre- NDA meetings, including inconsistent conclusions reflected in the official meeting minutes from the FDA; the inherent risks of clinical development of Gimoti, in particular since the Phase 3 trial failed to reach its primary endpoint in the ITT population; Evoke is entirely dependent on the success of Gimoti, and Evoke cannot be certain that it will be able to submit an NDA for Gimoti or obtain regulatory approval for or successfully commercialize Gimoti; risks associated with manufacturing new formulations of Gimoti for use in the PK trial; Evoke’s dependence on third parties for the manufacture of Gimoti as well as the conduct of the PK trial; Evoke may require additional funding to complete the PK trial and submit the NDA, and will require substantial additional funding to commercialize Gimoti, and may be unable to raise capital when needed, including to fund ongoing operations; Evoke may not be able to successfully commercialize Gimoti, if approved, as a result of risks associated with market acceptance, coverage and reimbursement and competing products; and other risks detailed in Evoke's prior press releases and in the periodic reports it files with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Evoke undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.


SOLANA BEACH, Calif., May 10, 2017 (GLOBE NEWSWIRE) -- Evoke Pharma, Inc. (NASDAQ:EVOK), a specialty pharmaceutical company focused on treatments for gastrointestinal (GI) diseases, today announced that data from its Phase 3 trial of Gimoti™, its patented nasal delivery of metoclopramide for the relief of symptoms associated with acute and recurrent diabetic gastroparesis in women, were presented at the Digestive Disease Week® (DDW) 2017 Meeting held in Chicago, Illinois. The poster presentation entitled “Symptom Severity Influences Drug Efficacy in Women with Diabetic Gastroparesis: Results of a Phase 3 Study with Metoclopramide Nasal Spray” illustrated that patients with moderate to severe symptoms at study entry, which included 105 of the 205 patients (51%) enrolled in the study, responded clinically and statistically significantly better to Gimoti than placebo at multiple time points in the Intent-to-Treat (ITT) and Per Protocol populations. Focusing on the benefits in patients with moderate to severe symptoms is consistent with the U.S. Food and Drug Administration (FDA) guidance on the clinical evaluation of drugs for the treatment of gastroparesis issued in July 2015 (Gastroparesis: Clinical Evaluation of Drugs for Treatment, Draft Guidance). In the Phase 3 trial, Gimoti was particularly effective in reducing nausea and upper abdominal pain, the most common and debilitating symptoms in patients with moderate to severe symptoms. This was similar to the benefits experienced by female patients in the Company’s Phase 2b trial. Safety data from the Phase 3 trial were consistent with favorable results from previous Gimoti studies. In particular, there were no adverse events of special interest, such as the central nervous system (CNS) effects observed with oral and parenteral formulations of metoclopramide. Based on recent FDA discussions, these data are anticipated to be submitted as part of a new drug application (NDA) for Gimoti. “As we prepare our 505(b)(2) NDA for Gimoti, including a comparative exposure pharmacokinetic (PK) study, acceptance of our Phase 3 data as a late breaker for poster presentation at DDW 2017 provided another opportunity for us to share the clinical importance of metoclopramide nasal spray for women suffering from the symptoms of moderate to severe diabetic gastroparesis,” stated Marilyn R. Carlson, DMD, MD, Chief Medical Officer. “We are very pleased that DDW accepted this data for presentation as we believe it is among the most up-to‑the-minute and novel GI developments that will impact research and the care of patients.” The Phase 3 trial was a U.S. multicenter, randomized, double-blind, placebo-controlled, parallel‑group study of the efficacy and safety of Gimoti compared to placebo in adult female subjects with symptomatic diabetic gastroparesis and delayed gastric emptying. Eligible patients were randomized 1:1 between Gimoti or placebo administered as a single nasal spray four times daily; 30 minutes before meals and at bedtime for a total of four weeks. The primary endpoint was the change in the total symptom score from baseline to week four. The trial data was not statistically significant in the ITT group (N=205, p=0.881). The authors of the presentation were Richard W. McCallum, MD, Texas Tech University Health Sciences Center, El Paso, Texas; Ronnie Fass, MD, Case Western Reserve University, Cleveland, Ohio; Bal R. Bhandari, MD, Delta Research Partners, Monroe, Louisiana; Marilyn R. Carlson, DMD, MD and Wayne M. Alves, PhD, Evoke Pharma, Inc., Solana Beach, California. The data poster is available on the investors section of the Company’s website, http://investor.evokepharma.com/, under the “Presentations and Posters” section. Evoke is a specialty pharmaceutical company focused primarily on the development of drugs to treat GI disorders and diseases. The Company is developing Gimoti, a metoclopramide nasal spray for the relief of symptoms associated with acute and recurrent gastroparesis in women with diabetes mellitus. Diabetic gastroparesis is a GI disorder afflicting millions of sufferers worldwide, in which the stomach takes too long to empty its contents resulting in serious digestive system symptoms. Metoclopramide is the only product currently approved in the United States to treat gastroparesis, and is currently available only in oral and intravenous forms. Gimoti is a novel formulation of this drug, designed to provide systemic delivery of metoclopramide through nasal administration. Visit www.EvokePharma.com for more information. Evoke cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negatives of these terms or other similar expressions. These statements are based on the company's current beliefs and expectations. These forward-looking statements include statements regarding: Evoke’s plans to present at DDW and discuss the data from its Phase 3 trial for Gimoti; the benefits Gimoti may have for patients with moderate to severe gastroparesis symptoms; the timing of any 505(b) (2) NDA submission for Gimoti with the FDA; the Company’s plans to conduct the comparative exposure PK study and include the results in the Gimoti NDA; and the utility of the Gimoti data to scientists and clinicians at DDW. The inclusion of forward-looking statements should not be regarded as a representation by Evoke that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Evoke's business, including, without limitation: risks associated with successfully commencing and receiving favorable results from the planned PK trial; later developments with the FDA that may be inconsistent with the already completed pre- NDA meetings, including inconsistent conclusions reflected in the official meeting minutes from the FDA; the inherent risks of clinical development of Gimoti, in particular since the Phase 3 trial failed to reach its primary endpoint in the ITT population; Evoke is entirely dependent on the success of Gimoti, and Evoke cannot be certain that it will be able to submit an NDA for Gimoti or obtain regulatory approval for or successfully commercialize Gimoti; risks associated with manufacturing new formulations of Gimoti for use in the PK trial; Evoke’s dependence on third parties for the manufacture of Gimoti as well as the conduct of the PK trial; Evoke may require additional funding to complete the PK trial and submit the NDA, and will require substantial additional funding to commercialize Gimoti, and may be unable to raise capital when needed, including to fund ongoing operations; Evoke may not be able to successfully commercialize Gimoti, if approved, as a result of risks associated with market acceptance, coverage and reimbursement and competing products; and other risks detailed in Evoke's prior press releases and in the periodic reports it files with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Evoke undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.


SOLANA BEACH, Calif., May 10, 2017 (GLOBE NEWSWIRE) -- Evoke Pharma, Inc. (NASDAQ:EVOK), a specialty pharmaceutical company focused on treatments for gastrointestinal (GI) diseases, today announced that data from its Phase 3 trial of Gimoti™, its patented nasal delivery of metoclopramide for the relief of symptoms associated with acute and recurrent diabetic gastroparesis in women, were presented at the Digestive Disease Week® (DDW) 2017 Meeting held in Chicago, Illinois. The poster presentation entitled “Symptom Severity Influences Drug Efficacy in Women with Diabetic Gastroparesis: Results of a Phase 3 Study with Metoclopramide Nasal Spray” illustrated that patients with moderate to severe symptoms at study entry, which included 105 of the 205 patients (51%) enrolled in the study, responded clinically and statistically significantly better to Gimoti than placebo at multiple time points in the Intent-to-Treat (ITT) and Per Protocol populations. Focusing on the benefits in patients with moderate to severe symptoms is consistent with the U.S. Food and Drug Administration (FDA) guidance on the clinical evaluation of drugs for the treatment of gastroparesis issued in July 2015 (Gastroparesis: Clinical Evaluation of Drugs for Treatment, Draft Guidance). In the Phase 3 trial, Gimoti was particularly effective in reducing nausea and upper abdominal pain, the most common and debilitating symptoms in patients with moderate to severe symptoms. This was similar to the benefits experienced by female patients in the Company’s Phase 2b trial. Safety data from the Phase 3 trial were consistent with favorable results from previous Gimoti studies. In particular, there were no adverse events of special interest, such as the central nervous system (CNS) effects observed with oral and parenteral formulations of metoclopramide. Based on recent FDA discussions, these data are anticipated to be submitted as part of a new drug application (NDA) for Gimoti. “As we prepare our 505(b)(2) NDA for Gimoti, including a comparative exposure pharmacokinetic (PK) study, acceptance of our Phase 3 data as a late breaker for poster presentation at DDW 2017 provided another opportunity for us to share the clinical importance of metoclopramide nasal spray for women suffering from the symptoms of moderate to severe diabetic gastroparesis,” stated Marilyn R. Carlson, DMD, MD, Chief Medical Officer. “We are very pleased that DDW accepted this data for presentation as we believe it is among the most up-to‑the-minute and novel GI developments that will impact research and the care of patients.” The Phase 3 trial was a U.S. multicenter, randomized, double-blind, placebo-controlled, parallel‑group study of the efficacy and safety of Gimoti compared to placebo in adult female subjects with symptomatic diabetic gastroparesis and delayed gastric emptying. Eligible patients were randomized 1:1 between Gimoti or placebo administered as a single nasal spray four times daily; 30 minutes before meals and at bedtime for a total of four weeks. The primary endpoint was the change in the total symptom score from baseline to week four. The trial data was not statistically significant in the ITT group (N=205, p=0.881). The authors of the presentation were Richard W. McCallum, MD, Texas Tech University Health Sciences Center, El Paso, Texas; Ronnie Fass, MD, Case Western Reserve University, Cleveland, Ohio; Bal R. Bhandari, MD, Delta Research Partners, Monroe, Louisiana; Marilyn R. Carlson, DMD, MD and Wayne M. Alves, PhD, Evoke Pharma, Inc., Solana Beach, California. The data poster is available on the investors section of the Company’s website, http://investor.evokepharma.com/, under the “Presentations and Posters” section. Evoke is a specialty pharmaceutical company focused primarily on the development of drugs to treat GI disorders and diseases. The Company is developing Gimoti, a metoclopramide nasal spray for the relief of symptoms associated with acute and recurrent gastroparesis in women with diabetes mellitus. Diabetic gastroparesis is a GI disorder afflicting millions of sufferers worldwide, in which the stomach takes too long to empty its contents resulting in serious digestive system symptoms. Metoclopramide is the only product currently approved in the United States to treat gastroparesis, and is currently available only in oral and intravenous forms. Gimoti is a novel formulation of this drug, designed to provide systemic delivery of metoclopramide through nasal administration. Visit www.EvokePharma.com for more information. Evoke cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negatives of these terms or other similar expressions. These statements are based on the company's current beliefs and expectations. These forward-looking statements include statements regarding: Evoke’s plans to present at DDW and discuss the data from its Phase 3 trial for Gimoti; the benefits Gimoti may have for patients with moderate to severe gastroparesis symptoms; the timing of any 505(b) (2) NDA submission for Gimoti with the FDA; the Company’s plans to conduct the comparative exposure PK study and include the results in the Gimoti NDA; and the utility of the Gimoti data to scientists and clinicians at DDW. The inclusion of forward-looking statements should not be regarded as a representation by Evoke that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Evoke's business, including, without limitation: risks associated with successfully commencing and receiving favorable results from the planned PK trial; later developments with the FDA that may be inconsistent with the already completed pre- NDA meetings, including inconsistent conclusions reflected in the official meeting minutes from the FDA; the inherent risks of clinical development of Gimoti, in particular since the Phase 3 trial failed to reach its primary endpoint in the ITT population; Evoke is entirely dependent on the success of Gimoti, and Evoke cannot be certain that it will be able to submit an NDA for Gimoti or obtain regulatory approval for or successfully commercialize Gimoti; risks associated with manufacturing new formulations of Gimoti for use in the PK trial; Evoke’s dependence on third parties for the manufacture of Gimoti as well as the conduct of the PK trial; Evoke may require additional funding to complete the PK trial and submit the NDA, and will require substantial additional funding to commercialize Gimoti, and may be unable to raise capital when needed, including to fund ongoing operations; Evoke may not be able to successfully commercialize Gimoti, if approved, as a result of risks associated with market acceptance, coverage and reimbursement and competing products; and other risks detailed in Evoke's prior press releases and in the periodic reports it files with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Evoke undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.


I hypothesize here that the ability of probiotics to synthesize neuroactive compounds provides a unifying microbial endocrinology-based mechanism to explain the hitherto incompletely understood action of commensal microbiota that affect the host's gastrointestinal and psychological health. Once ingested, probiotics enter an interactive environment encompassing microbiological, immunological, and neurophysiological components. By utilizing a trans-disciplinary framework known as microbial endocrinology, mechanisms that would otherwise not be considered become apparent since any candidate would need to be shared among all three components. The range of neurochemicals produced by probiotics includes neurochemicals for which receptor-based targets on immune and neuronal elements (intestinal and extra-intestinal) have been well characterized. Production of neurochemicals by probiotics therefore allows for their consideration as delivery vehicles for neuroactive compounds. This unifying microbial endocrinology-based hypothesis, which may facilitate the selection and design of probiotics for clinical use, also highlights the largely unrecognized role of neuroscience in understanding how microbes may influence health. Editor's suggested further reading in BioEssays Harvesting the biological potential of the human gut microbiome Abstract Probiotics are capable of producing neurochemicals such as acetylcholine or dopamine that may influence a human's gastrointestinal and psychological health by binding to receptors on immune and neuronal cells. © 2011 WILEY Periodicals, Inc.


Grammas P.,Texas Tech University Health Sciences Center
Expert reviews in molecular medicine | Year: 2011

Diseases of the central nervous system (CNS) pose a significant health challenge, but despite their diversity, they share many common features and mechanisms. For example, endothelial dysfunction has been implicated as a crucial event in the development of several CNS disorders, such as Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, multiple sclerosis, human immunodeficiency virus (HIV)-1-associated neurocognitive disorder and traumatic brain injury. Breakdown of the blood-brain barrier (BBB) as a result of disruption of tight junctions and transporters, leads to increased leukocyte transmigration and is an early event in the pathology of these disorders. The brain endothelium is highly reactive because it serves as both a source of, and a target for, inflammatory proteins and reactive oxygen species. BBB breakdown thus leads to neuroinflammation and oxidative stress, which are implicated in the pathogenesis of CNS disease. Furthermore, the physiology and pathophysiology of endothelial cells are closely linked to the functioning of their mitochondria, and mitochondrial dysfunction is another important mediator of disease pathology in the brain. The high concentration of mitochondria in cerebrovascular endothelial cells might account for the sensitivity of the BBB to oxidant stressors. Here, we discuss how greater understanding of the role of BBB function could lead to new therapeutic approaches for diseases of the CNS that target the dynamic properties of brain endothelial cells.


Gonzalez R.,Texas Tech University Health Sciences Center
Journal of Clinical Psychiatry | Year: 2014

Background: Rhythm disruption is a core feature of bipolar disorder and it has been hypothesized that disturbances of the circadian timing system play a fundamental role in the etiology of the disorder. Objective: We sought to investigate (1) theoretical models for biological rhythm disruptions in bipolar disorde (2) physiological disturbances of biological rhythms in bipolar disorder, (3) clinical and therapeutic implications of biological rhythm disturbances in bipolar disorder, and (4) associations between circadian gene variations and bipolar disorder DataSources: PubMed database was searched systematically for articles that were published on or before May 5, 2013, and were written in English using the terms bipolardisorder, clock genes, endogenous clock, molecular clock, biological rhythms, circadian, suprachiasmatic nucleus, circadian rhythm, melatonin, and sleep. Study Selection: Seventy-four articles highlighting the objectives were included in the review. Data Extraction: Data regarding exploring the association between bipolar disorder and circadian and chronobiological phenomena were reviewed and findings summarized. Results:The literature reviewed suggests that circadian rhythm disturbance may be a feature of bipolar disorder Conclusions: In toto, the literature suggests that circadian rhythm disturbances may be a feature of bipolar disorderlhis area of research has received theoretical consideration as playing a significant role in the pathophysiology of the illness but has been understudied to this point. Further research in the field is warranted. © 2014 Physicians Postgraduate Press, Inc.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: BIOMATERIALS PROGRAM | Award Amount: 398.32K | Year: 2015

Nontechnical:

This award by the Biomaterials Program in the Division of Materials Research to Colorado School of Mines aims to overcome the materials challenge on harnessing membrane protein (MP) functions in engineered systems. MPs represent a family of biologically-derived and bio-renewable high-performance nanomaterials that are largely unexplored. These proteins are the gate-keepers of cells, and are involved in critical life processes, such as energy conversion, matter transport and information processing. These same MP-mediated functions are also highly coveted nanoengineering feats in synthetic systems. Exploiting MPs for nanoengineering may help understand, predict, and ultimately control recognition and transport at the nanoscale, but is greatly impeded by the fluidic and labile nature of biomembranes. This study bridges the gap between biotic and abiotic systems by developing chemically versatile synthetic membranes to support MP functions. The successful outcome of this study will help unleash the full potential of MPs to create novel nanotechnologies ranging from solar conversion to high throughput diagnostics. With respect to broad impact on education, this project builds a multi-tiered education program on renewable materials. The objective of this program is to bring societal awareness on sustainability, and motivate undergraduate and K-12 students to pursue career paths on bio-renewable materials. A focused outreach component, Summer Experience @ Mines, targets minority students at a local high school by hosting their first exposure to engineering studies and college life, and develop curriculum materials for their Biotechnology class. A broader outreach component includes training K-12 science teachers and dissemination of the curriculum materials to local and nearby school districts.


Technical:

This award is to develop bio-hybrid materials with membrane-protein-mediated transport performance. Membrane proteins (MPs) are biologically-derived and bio-renewable high-performance nanomaterials. Despite numerous proof-of-concept demonstrations of MPs great potential in engineered systems, little is known on how to design synthetic MP-supporting membranes that balance a dichotomy between fluidity and stability, and how to direct spontaneous MP reconstitution into these robust membranes to form 2-dimensional (2-D) or 3-D proteomembrane arrays. Using proteorhodopsin, a light-driven proton pump as a model, this study will elucidate: (1) the directed assembly principles to reconstitute proteorhodopsin into hierarchically organized proteomembrane arrays; and (2) the roles of synthetic membranes in shaping proteorhodopsin function. Since proteorhodopsin has a common seven transmembrane (7 TM) architecture of G protein-coupled receptors, a large family of MPs that regulate energy conversion, matter transport and biosensing. The guiding concepts learnt from this study have the potential to benefit a broad range of MP-based nanotechnologies. This multidisciplinary study provides ample opportunities to train students at the interdisciplinary area of materials engineering, synthetic chemistry, biophysics, and protein engineering. With this award, this research group will design a multi-tiered soft matter education program entitled Renewable Materials for Sustainable Future. This program aims to: (1) improve educational components on soft matter by course development; (2) support undergraduate students from the Undergraduate Research Opportunity Program, the Society of Women Engineering, and International Exchange Students Program to have hands-on research experience; and (3) build regular and systematic outreach activities to K-12 students in local and nearby school districts.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: Cellular Dynamics and Function | Award Amount: 825.00K | Year: 2015

Cells maintain large differences in the concentration of ions (electrically charged atoms or molecules) across the membrane that separates the cell from its environment. This concentration difference is used to drive many essential cellular processes and it is established and maintained by numerous membrane pumps, which are proteins responsible for transporting these ions across the membrane. This project will engage undergraduate students (including members of minorities underrepresented in science) and graduate students in investigations of the fundamental properties by which a particular membrane pump selects and transports sodium and potassium ions across membranes. In addition to training in biophysical techniques, the students will be supported to attend national scientific meetings at which they will be able to present the results of their research.

The Na/K pump is electrogenic because it transports 3 Na+ out of the cell in exchange for 2 K+, in each catalytic cycle. One out of three sites can exclusively bind Na+ (a feature that distinguishes the Na/K pump from other P-type ATPases). All P-type ATPases alternate between two major conformations, E1 with inward facing ion binding sites and E2 with outward facing ion binding sites. The molecular mechanisms of ion selectivity by the Na/K pump remain unclear, yet knowledge of these is critical to an understanding of how these proteins couple the chemical energy of ATP hydrolysis to the mechanical work required for ion translocation. This project will study the mechanisms of ion selection in the Na/K pump with an innovative approach that integrates high-temporal-resolution electrophysiology, computational chemistry and biochemistry. The available crystal structures and results from our laboratory will be used to generate hypotheses with respect to (a) Elucidating the mechanisms of ion selectivity in the two major pump conformations; (b) Determining the order of intracellular Na+ binding and external Na+ release; and (c) Identifying the pathway and mechanisms of uncoupled H+ influx through Na/K pumps.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: CDS&E-MSS | Award Amount: 45.00K | Year: 2016

This project aims to develop a system of statistical analysis tools to tackle several important challenges in analysis of complex bioinformatics data, which involves a variety of response variables and tens of thousands independent variables. The interest often lies in identifying the key independent variables associated with the response variables, and understanding such associations as well as the interactions among the independent variables.

The extreme magnitude and complexity of bioinformatics data have posed serious challenges for data analysis. To overcome these challenges, we propose (i) to systematically and properly integrate multi-scale data before we can apply our novel modeling and analysis methods since the data we explore are collected by numerous independent studies at phenotypic, cellular, protein, and genetic levels with information from very different time and dimension scales; (ii) to develop feature screening criteria for a mixed type of longitudinal data using the combination of correlation tests in bivariate longitudinal regression models and the Benjamini-Hochberg-Yekutieli procedure, (iii) to develop graphical models that allow the variables being a mix of continuous and discrete longitudinal variables, with the nodes representing variables and each edge indicating the dependence of the two relevant variables conditional on the other variables; and (iv) to investigate the functioning form of each predictor by resorting to the data themselves under the framework of a mixed effects regression model with a continuous or discrete response and a high dimensional vector of predictors, with the resulting procedure allowing a user to simultaneously determine the form of each predictor effect to be zero, linear or nonlinear.


Gupta P.,Texas Tech University Health Sciences Center
BMC medicine | Year: 2012

HER2 is an oncogene, expression of which leads to poor prognosis in 30% of breast cancer patients. Although trastuzumab is apparently an effective therapy against HER2-positive tumors, its systemic toxicity and resistance in the majority of patients restricts its applicability. In this study we evaluated the effects of phenethyl isothiocyanate (PEITC) in HER2-positive breast cancer cells. MDA-MB-231 and MCF-7 breast cancer cells stably transfected with HER2 (high HER2 (HH)) were used in this study. The effect of PEITC was evaluated using cytotoxicity and apoptosis assay in these syngeneic cells. Western blotting was used to delineate HER2 signaling. SCID/NOD mice were implanted with MDA-MB-231 (HH) xenografts. Our results show that treatment of MDA-MB-231 and MCF-7 cells with varying concentrations of PEITC for 24 h extensively reduced the survival of the cells with a 50% inhibitory concentration (IC50) of 8 μM in MDA-MB-231 and 14 μM in MCF-7 cells. PEITC treatment substantially decreased the expression of HER2, epidermal growth factor receptor (EGFR) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr-705. The expression of BCL-2-associated × (BAX) and BIM proteins were increased, whereas the levels of B cell lymphoma-extra large (BCL-XL) and X-linked inhibitor of apoptosis protein (XIAP) were significantly decreased in both the cell lines in response to PEITC treatment. Substantial cleavage of caspase 3 and poly-ADP ribose polymerase (PARP) were associated with PEITC-mediated apoptosis in MDA-MB-231 and MCF-7 cells. Notably, transient silencing of HER2 decreased and overexpressing HER2 increased the effects of PEITC. Furthermore, reactive oxygen species (ROS) generation, mitochondrial depolarization and apoptosis by PEITC treatment were much higher in breast cancer cells expressing higher levels of HER2 (HH) as compared to parent cell lines. The IC50 of PEITC following 24 h of treatment was reduced remarkably to 5 μM in MDA-MB-231 (HH) and 4 μM in MCF-7 (HH) cells, stably overexpressing HER2. Oral administration of 12 μM PEITC significantly suppressed the growth of breast tumor xenografts in SCID/NOD mice. In agreement with our in vitro results, tumors from PEITC-treated mice demonstrated reduced HER2, EGFR and STAT3 expression and increased apoptosis as revealed by cleavage of caspase 3 and PARP. In addition our results show that PEITC can enhance the efficacy of doxorubicin. Our results show a unique specificity of PEITC in inducing apoptosis in HER2-expressing tumor cells in vitro and in vivo and enhancing the effects of doxorubicin. This unique specificity of PEITC offers promise to a subset of breast cancer patients overexpressing HER2.

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