Southwestern Medical Center at Dallas
Southwestern Medical Center at Dallas
News Article | February 15, 2017
CITY OF INDUSTRY, CA--(Marketwired - Feb 14, 2017) - Marina Biotech, Inc. ( : MRNA), a biopharmaceutical company focused on the development and commercialization of innovative therapeutics for disease intersections of arthritis, hypertension and cancer, today announced the appointment of Larn Hwang, Ph.D. as Chief Scientific Officer and Mihir Munsif as Chief Operating Officer. "We are thrilled to have Larn and Mihir join the Marina Biotech team," stated Joseph W. Ramelli, CEO of Marina Biotech. "Each of them brings a track record of success and important skill sets that I believe will prove invaluable for Marina at this important inflection point in the company's history. Larn will bring with her extensive experience in oligo-therapeutics and Mihir will lead the manufacturing of our drug products." Dr. Hwang has served as the Chief Executive Officer of Oncotelic, Inc. since October 2015 and as the Chief Scientific Officer of Autotelic Inc. since October 2013. Dr. Hwang is a veteran in the drug development industry, with broad expertise in drug discovery and biomarker development, as well as clinical and regulatory operations. Dr. Hwang was a founder of IgDraSol, Inc. (which merged with Sorrento Therapeutics in 2013, where she later served as VP of Regulatory and Clinical Operations from September 2013 to May 2014) and served as its Chief Operating Officer from April 2012 to August 2013, and she was a founder of Biomiga Diagnostics and served as its Chief Operating Officer from 2011 to August 2013. Prior to that, she served as Head of Cell Biology at Abraxis BioScience from November 2005 to June 2011 and as Senior Principal Scientist at Celgene Corporation from February 2011 to June 2011. Dr. Hwang made significant contributions to the field of antisense and miRNA with several patents applications filed on her work. Dr. Hwang has also held positions with Johnson & Johnson and ABI. Dr. Hwang received a Ph.D. in Molecular Microbiology from The University of Texas Southwestern Medical Center at Dallas. Mr. Munsif has served as the Senior Vice President at Autotelic Inc. since November 2016, as the Senior Vice President of Portfolio Management of LipoMedics, Inc. since June 2016 and as the Senior Vice President of Portfolio Management of Oncotelic, Inc. since October 2015. Previously he served as the Chief Executive Officer of IthenaPharma Inc. from August 2016 until its merger with Marina Biotech in 2016, and as the Chief Operating Officer of IthenaPharma Inc. from September 2014 until August 2016. Prior to that, he served as Product Life Cycle Management and Supply Chain Consulting at Accenture from March 2013 until September 2014 and as Product Life Cycle Management and Supply Chain Management Operations at Herbalife from April 2009 until March 2013. Mr. Munsif received a M.S. in Industrial Engineering from the University of Oklahoma and a B.S. in Chemical Engineering from Manipal Institute of Technology. About Marina Biotech, Inc. Marina Biotech is a biotechnology company focused on the development and commercialization of innovative therapeutics for disease intersections of arthritis, hypertension, and cancer. Our pipeline includes combination therapies of oligonucleotide-based therapeutics and small molecules. The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome). By its merger with IthenaPharma, Marina Biotech recently acquired IT-102/IT-103 -- next generation celecoxib -- which will be developed together with CEQ508 as a therapeutic enhancer for therapies against FAP and CRC. IT-102/IT-103 are also being developed for the treatment of combined arthritis/ hypertension and treatment of pain requiring high dose of celecoxib. Additional information about Marina Biotech is available at http://www.marinabio.com. Marina Biotech Forward-Looking Statements Statements made in this news release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested. Factors that could cause actual results to differ materially from those in forward-looking statements include, but are not limited to: (i) the ability of Marina Biotech to successfully integrate its business operations with those of IthenaPharma; (ii) the ability of Marina Biotech to obtain funding to support its clinical development; (iii) the ability of Marina Biotech to attract and/or maintain manufacturing, research, development and commercialization partners; (iv) the ability of Marina Biotech and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (v) the ability of Marina Biotech and/or a partner to obtain required governmental approvals; and (vi) the ability of Marina Biotech and/or a partner to develop and commercialize products prior to, and that can compete favorably with those of, competitors. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in Marina Biotech's most recent filings with the Securities and Exchange Commission. Marina Biotech assumes no obligation to update or supplement forward-looking statements because of subsequent events.
Dyer J.S.,Ohio State University |
Rosenfeld C.R.,Southwestern Medical Center at Dallas
Seminars in Reproductive Medicine | Year: 2011
Epidemiological studies have suggested that metabolic programming is one of the critical factors contributing to the etiology of obesity as well as concurrent increase in related chronic diseases (e.g., type 2 diabetes and cardiovascular disease). Metabolic programming is the phenomenon whereby a nutritional stress/stimulus applied during critical periods of early development permanently alters an organism's physiology and metabolism, the consequences of which are often observed much later in life. The idea of metabolic programming originated from the fetal origins hypothesis proposed by Barker in which he suggested that disproportionate size at birth of the newborn due to an adverse intrauterine environment correlated well with an increased risk of adult-onset ill health outcomes (type 2 diabetes, hypertension, and cardiovascular disease). The fetal origins hypothesis, proposed by Barker, suggests that adequate nutrition during fetal development is critical. Overnutrition is a form of malnutrition that has increased in the United States over the past several decades in which nutrients are oversupplied relative to the amounts required for normal growth, development, and metabolism. Evidence for the effects of maternal obesity and overnutrition on metabolic programming is reviewed during critical prenatal, perinatal, and postnatal periods. Copyright © 2011 by Thieme Medical Publishers, Inc.
Walker D.,Southwestern Medical Center at Dallas
Seminars in cutaneous medicine and surgery | Year: 2011
Dermatologists are presented with a diversity of therapeutic modalities for the treatment of inflammatory, sclerosing, and neoplastic conditions, but with the development of various new irradiation devices that utilize specific parts of the electromagnetic spectrum, phototherapy has become a more viable, accessible, and efficacious option in the treatment of these conditions. The ultraviolet (UV) range (10-400 nm) is further subdivided into UVA and UVB, each of which has been particularly useful in a number of skin conditions. The most commonly used forms of UV irradiation are UVA1, psoralen plus UVA (PUVA), and narrowband (NB) UVB. Each of these modalities differ in their mechanism of action, indications, and side effect profiles, and it is important that clinicians be familiar with these differences. Today, phototherapy is a valuable option in the treatment of many nonpsoriatic conditions including atopic dermatitis, sclerosing skin conditions such as morphea, vitiligo, and mycosis fungoides. Due to its relative safety, phototherapy may be used in most populations, including children and pregnant women. However, contraindications and side effects are known and should be considered before patients begin a phototherapeutic regimen. Copyright © 2011 Elsevier Inc. All rights reserved.
Marple B.F.,Southwestern Medical Center at Dallas
American Journal of Rhinology and Allergy | Year: 2010
Background: Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional "unified airway" respiratory inflammation model on diagnosis and treatment of inflammatory airway disease. Methods: MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx. Results: Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion. Conclusion: Epidemiological concordance of AR with several airway diseases conforms to a bidirectional "unified airway" respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions. Copyright © 2010, OceanSide Publications, Inc.
Liu J.,Southwestern Medical Center at Dallas |
Hu J.,Southwestern Medical Center at Dallas |
Corey D.R.,Southwestern Medical Center at Dallas
Nucleic Acids Research | Year: 2012
Double-stranded RNAs are powerful agents for silencing gene expression in the cytoplasm of mammalian cells. The potential for duplex RNAs to control expression in the nucleus has received less attention. Here, we investigate the ability of small RNAs to redirect splicing. We identify RNAs targeting an aberrant splice site that restore splicing and production of functional protein. RNAs can target sequences within exons or introns and affect the inclusion of exons within SMN2 and dystrophin, genes responsible for spinal muscular atrophy and Duchenne muscular dystrophy, respectively. Duplex RNAs recruit argonaute 2 (AGO2) to pre-mRNA transcripts and altered splicing requires AGO2 expression. AGO2 promotes transcript cleavage in the cytoplasm, but recruitment of AGO2 to pre-mRNAs does not reduce transcript levels, exposing a difference between cytoplasmic and nuclear pathways. Involvement of AGO2 in splicing, a classical nuclear process, reinforces the conclusion from studies of RNA-mediated transcriptional silencing that RNAi pathways can be adapted to function in the mammalian nucleus. These data provide a new strategy for controlling splicing and expand the reach of small RNAs within the nucleus of mammalian cells. © 2011 The Author(s).
Kasumu A.,Southwestern Medical Center at Dallas |
Bezprozvanny I.,Southwestern Medical Center at Dallas
Cerebellum | Year: 2012
Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 30 autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by progressive ataxia and cerebellar atrophy. Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, 17 different gene loci have so far been implicated as culprits in these SCAs. It is not currently understood how mutations in these 17 proteins lead to the cerebellar atrophy and ataxia. Several pathogenic mechanisms have been studied in SCAs but there is yet to be a promising target for successful treatment of SCAs. Emerging research suggests that a fundamental cellular signaling pathway is disrupted by a majority of these mutated genes, which could explain the characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. We propose that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells either as a result of an excitotoxic increase or a compensatory suppression of calcium signaling. We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic sympoms and eventually proceed to Purkinje cell death. Here, we discuss a calcium hypothesis of Purkinje cell neurodegeneration in SCAs by primarily focusing on an example of spinocerebellar ataxia 2 (SCA2). We will also present evidence linking deranged calcium signaling to the pathogenesis of other SCAs (SCA1, 3, 5, 6, 14, 15/16) that lead to significant Purkinje cell dysfunction and loss in patients. © Springer Science+Business Media, LLC 2010.
Lehrman M.A.,Southwestern Medical Center at Dallas
Trends in Biochemical Sciences | Year: 2015
The mechanism for flipping large lipid-linked oligosaccharides across membranes has remained a paradox. Perez. et al. now report the structure of the PglK protein of. C. jejuni, a flippase for a bacterial lipid-linked oligosaccharide, and reveal an unexpected whip-like mechanism. © 2015 Elsevier Ltd.
Iscla I.,Southwestern Medical Center at Dallas |
Blount P.,Southwestern Medical Center at Dallas
Biophysical Journal | Year: 2012
Mechanosensors are important for many life functions, including the senses of touch, balance, and proprioception; cardiovascular regulation; kidney function; and osmoregulation. Many channels from an assortment of families are now candidates for eukaryotic mechanosensors and proprioception, as well as cardiovascular regulation, kidney function, and osmoregulation. Bacteria also possess two families of mechanosensitive channels, termed MscL and MscS, that function as osmotic emergency release valves. Of the two channels, MscL is the most conserved, most streamlined in structure, and largest in conductance at 3.6 nS with a pore diameter in excess of 30 Å; hence, the structural changes required for gating are exaggerated and perhaps more easily defined. Because of these properties, as well as its tractable nature, MscL represents a excellent model for studying how a channel can sense and respond to biophysical changes of a lipid bilayer. Many of the properties of the MscL channel, such as the sensitivity to amphipaths, a helix that runs along the membrane surface and is connected to the pore via a glycine, a twisting and turning of the transmembrane domains upon gating, and the dynamic changes in membrane interactions, may be common to other candidate mechanosensors. Here we review many of these properties and discuss their structural and functional implications. © 2012 by the Biophysical Society.
Zhong D.,Southwestern Medical Center at Dallas |
Blount P.,Southwestern Medical Center at Dallas
Biochemistry | Year: 2013
The bacterial mechanosensitive channel of large conductance (MscL) directly senses and responds to membrane tension. It serves as an "emergency release valve" upon acute decreases in the osmotic environment, thus preventing cell lysis. It is one of the best studied mechanosensitive channels and serves as a paradigm of how a channel senses and responds to its membrane environment. The MscL protein is highly conserved, found throughout the bacterial kingdom, and has been shown to encode a functional mechanosensitive channel in all species where it has been studied. However, channels from different species have shown some functional variance; an extreme example is the Mycobacterium tuberculosis MscL, which when heterologously expressed in Escherichia coli requires significantly more membrane tension for gating than the endogenous E. coli MscL. We previously speculated that the membrane environment or factors not found in E. coli promoted the proper gating of the M. tuberculosis MscL channel in its native environment. Here, by reconstituting the M. tuberculosis and E. coli MscL channels in various lipids, we demonstrate that inclusion of phosphatidylinositol, a lipid found in M. tuberculosis but not E. coli, is sufficient for gating of the M. tuberculosis MscL channel within a physiological range of membrane tension. © 2013 American Chemical Society.
Pasipanodya J.,Southwestern Medical Center at Dallas |
Gumbo T.,Southwestern Medical Center at Dallas
Antimicrobial Agents and Chemotherapy | Year: 2011
Antimicrobial pharmacokinetic-pharmacodynamic (PK/PD) science and clinical trial simulations have not been adequately applied to the design of doses and dose schedules of antituberculosis regimens because many researchers are skeptical about their clinical applicability. We compared findings of preclinical PK/PD studies of current first-line antituberculosis drugs to findings from several clinical publications that included microbiologic outcome and pharmacokinetic data or had a dose-scheduling design. Without exception, the antimicrobial PK/PD parameters linked to optimal effect were similar in preclinical models and in tuberculosis patients. Thus, exposure-effect relationships derived in the preclinical models can be used in the design of optimal antituberculosis doses, by incorporating population pharmacokinetics of the drugs and MIC distributions in Monte Carlo simulations. When this has been performed, doses and dose schedules of rifampin, isoniazid, pyrazinamide, and moxifloxacin with the potential to shorten antituberculosis therapy have been identified. In addition, different susceptibility breakpoints than those in current use have been identified. These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration. Copyright © 2011, American Society for Microbiology. All Rights Reserved.