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Andrey L. Karamyshev

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Andrey L. Karamyshev CURRICULUM VITAE Andrey L. Karamyshev Assistant Professor Department of Cell Biology and Biochemistry! Texas Tech University Health Sciences Center! 3601 4th Street, Mail Stop 6540! Lubbock, TX 79430 Phone: (806) 743-4102 Fax: (806) 743-2990 e-mail: [email protected] EDUCATION: Postdoctoral Studies: Department of Tumor Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan (Advisor: Dr. Yoshikazu Nakamura). Department of Medical Biochemistry and Genetics, College of Medicine, Texas A&M University, College Station, TX (Advisor: Dr. Arthur E. Johnson). Ph.D. in Biochemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia. M.S., Biology, Kuban State University, Krasnodar, Russia. FIELDS OF SPECIALIZATION: Biochemistry, Molecular and Cellular Biology. RESEARCH INTERESTS Molecular mechanisms of human diseases. Post-transcriptional regulation of gene expression. Gene silencing and translational repression. mRNA and protein quality control. RNA stability and degradation. siRNAs/miRNAs. Prolactin, CFTR, secretory and membrane proteins. Protein translation, folding and transport. Protein-protein interactions. SCIENTIFIC PUBLICATIONS (see list below) 31 publications (total), including 25 full-length peer-reviewed papers in scientific journals, 5 articles in the Encyclopedia of Molecular Biology (Publisher: John Wiley & Sons, Inc., N.Y.), and chapter in a book. PRESENTATIONS (90 total, see lists below) Results were presented at various international and national meetings, conferences and symposia (58 presentations), as well as during invited or selected talks (32 talks) at different universities and meetings around the world. Andrey L. Karamyshev, Ph.D. RESEARCH EXPERIENCE AND POSITIONS 2016-present Assistant Professor (Tenure track), Department of Cell Biology and Biochemistry!, Texas Tech University Health Sciences Center!, Lubbock, TX. 2009-2016 Assistant Professor (Research track), Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX. 2006-2009 Senior Research Scientist, Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX. 2002-2006 Assistant Research Scientist, Department of Medical Biochemistry and Genetics, College of Medicine, Texas A&M University System Health Sciences Center, College Station, TX. 2000-2002 Postdoctoral Research Associate, Department of Medical Biochemistry and Genetics, College of Medicine, Texas A&M University System Health Sciences Center, College Station, TX. Advisor: Professor Arthur E. Johnson, Ph.D. 1996-1999 Postdoctoral Fellow: Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellow (1996-1998), then IMSUT Postdoctoral Fellow (1998-1999), Department of Tumor Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. Advisor: Professor Yoshikazu Nakamura, Ph.D. HONORS, AWARDS AND FELLOWSHIPS: • 2015 Alzheimer’s Disease Research Award. UT Southwestern Medical Center and The Friends of the Alzheimer’s Disease Center. • 2014 Featured in Nature Reviews Genetics: Research highlights: Novel mRNA quality control mechanism, vol. 15 (3), p. 144. • 2014 Featured in Trends in Biochemical Sciences: Popp, M. W.-L. and Maquat L. E. Defective secretory-protein mRNAs take the RAPP, vol. 39, No. 4, p. 154-156. • Selected speaker at the Gordon Research Conference on Translation Machinery in Health & Disease (2015), the Gordon Research Conference on Protein Transport Across Cell Membranes (2014), 26th North American Cystic Fibrosis Conference (2012), FASEB Scientific Research Conference (2012), 21st Res. Symposium Mol. Biophys. Graduate Program, UTSW Medical Center (2012), 20th Texas Protein Folders Meeting (2012), 19th Texas Protein Folders Meeting (2011), European Cystic Fibrosis Society Conference, Portugal (2008), 16th Texas Protein Folders Meeting (2008), 21st North American Cystic Fibrosis Conference (2007), MBTP Retreat (2005), Center for Advanced Biomolecular Research (CABR) Retreat (2003). • Selected speaker of the Department of Physiology Junior Scientist Seminar series (selection on the base of significance of work and excellent achievement) (2014). • Award for Best Poster at the 2008 European Cystic Fibrosis Society Conference: New Frontiers in Basic Science of Cystic Fibrosis, Regua, Douro, Portugal (2008). • Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship (1996-1998). • International Science Foundation (ISF) Fellowship for participation in the Cold Spring Harbor Meeting Molecular genetics of bacteria and phages, USA (1995). • NATO travel and living grant for participation in summer school Molecular dynamics of biomembranes, Cargese (Corse), France, (1995). • State Scientific Research Grant for Young Scientists of Russia (1993). • G. K. Skryabin Premium in Molecular Biology, Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences (1992). 2 Andrey L. Karamyshev, Ph.D. SUMMARY OF RESEARCH ACCOMPLISHMENTS My major accomplishment is a discovery of a novel pathway of translational regulation and protein quality control in which specific mRNA degradation preemptively regulates aberrant protein production (RAPP) (Karamyshev et al., 2014, Cell) [3, see references in my list of publications]1; the paper was highlighted in Nature Rev. Genet., in TIBS, and recommended by Faculty of 1000. Data indicate that RAPP is a general regulatory mechanisms controlling gene expression at the ribosome. This pathway monitors the status of nascent chains interactions during translation and transfers the signal to mRNA degradation machinery to prevent synthesis of proteins that lost these natural interactions. The data demonstrate that many human diseases may be a result of deregulation of RAPP. I also developed a new methodology for identification of proteins interacting with nascent chains, iPINCH, that is a powerful tool for identification of transient, short-lived interactions during translation. Recently I conducted detail analysis of interaction of SRP with altered signal sequences and deciphered the code for directing proteins for translocation across ER membrane (J. Mol. Biol., 2016) [2]. I am a co-corresponding author on the Cell paper, and corresponding author of the J. Mol. Biol. paper. We also discovered that a cystic fibrosis causing mutation in CFTR changes its interaction partners during translation, that influences mutant protein expression [1]. During my work in Arthur E. Johnson lab I discovered targeting function of SecA protein and proposed mechanism for protein sorting in bacteria [6, the paper has been recommended by Faculty of 1000]. I also conducted mapping the interactions of the STT3 subunit of the oligosaccharyl transferase complex with nascent chains in eukaryotes [5]. I was awarded JSPS (Japan Society for the Promotion of Science) Postdoctoral Fellowship for Foreign Researchers and worked in Japan in Dr. Yoshikazu Nakamura laboratory at the Department of Tumor Biology, Institute of Medical Science, University of Tokyo for three years. I was involved in the projects that were focused on the elucidation of molecular mechanisms of translation termination, reinitiation, and frameshifting [7-11, 17]. We found that reinitiation of protein synthesis is quantitatively regulated by the distance between stop and initiation codons [7]. As a major result of my work at the University of Tokyo a new release factor gene from Tetrahymena was cloned and studied [11, 17]. It was the first release factor cloned from ciliates. It was the first release factor with naturally restricted specificity, and it can recognize only one stop codon (UGA). In contrast to the most other organisms, Tetrahymena uses only one stop codon UGA and the other two codons, UAA and UAG, are decoded as glutamine codons. We have found that Tetrahymena release factor has unique alterations in its structure and proposed that its decoding specificity resides in the domain 1 of the protein. Later we showed that interactions within domain 1 modulate the decoding specificity of Tetrahymena release factor [9]. During my graduate school I was studying molecular mechanisms of protein secretion and processing in bacteria. I developed amber-suppressor mutagenesis approach (as an alternative to classical site-directed mutagenesis) to elucidate role of specific amino acid residues in protein secretion and processing [19, 21]. The approach is based on amber-stop codon suppression in the cells expressing a gene of interest containing amber-stop mutation and an appropriate amber-suppressor tRNA. In addition to bacterial amber-suppressors we generated a set of phage T5 amber-suppressors [20]. I discovered that N-terminus of signal sequence of a secretory protein provides translocation efficiency [18, 21, 24, 26], while C- terminal part is important for signal sequence cleavage by a leader peptidase [19, 22, 26]. We also showed that alkaline phosphatase is secreted outside of the cells by a secretory vesicles mechanism [23, 26, 30- 31]. 1 All reference numbers correspond to those in the List of Publications 3 Andrey L. Karamyshev, Ph.D. INVITED AND SELECTED SEMINARS AND TALKS • Protein Quality Control During Translation in Health and Disease. Institute of Metabolic Disease, Baylor Research Institute. Dallas, TX, USA, June 20, 2016. Invited talk. Host: Dr. Jinsong Shen. • RAPP is a Pathway for Specific Degradation of mRNAs Encoding Aberrant Proteins. RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA, February 2, 2016. Invited talk. Host: Dr.
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