Mehmet Candas

Professional Preparation

Ph.D. - Molecular Biology and Genetics
Southern Methodist University Dallas, Texas - 1995

M.S. - Biochemistry
Middle East Technical University, Ankara, Turkey - 1988

B.S. - Biochemistry
Middle East Technical University, Ankara, Turkey - 1985

Research Areas

Research Background and Interests

After earning my bachelor’s and master's degrees with specialties in biochemistry and cancer biology, I completed my doctoral dissertation with studies focusing on glutathione metabolism and oxidative stress in the aging process. In 1995, I joined a biotechnology company and worked on recombinant protein expression and live-bacteria vaccine delivery technologies for immune stimulation, particularly for treatment of infectious diseases and cancer. In 1997, I became associated with The University of Texas at Dallas where I started as a research scientist and studied metabolic features of bacterial virulence expression. Later, in 1999-2006, I served as the Research Manager for Center for Applied Biology (Center for Biotechnology and Bioinformatics). During this time, I focused my studies on bacterial and insect systems as paradigms for microbe-host interactions and investigated structural and functional aspects of cell adhesion receptors in cell death signaling cascades. The studies provided new insight into the action of insecticidal Bt toxins as well as how changes in proteomic expression profiles in insect gut epithelium consolidate with physiological responses associated with resistance to biopesticides. At the Center, I also helped develop a spin-off company emphasizing agricultural and environmental biotechnology. As a scientific co-founder and internal scientific consultant to the company, I implemented an integrated technology platform involving genomic, proteomic and bioinformatic applications for constructing versatile gene libraries and generating protein expression systems for cell-based assays.

My current interests focus on overlapping themes that underline the metabolic basis of phenotypic adaptation and how cells integrate metabolic responses with signaling pathways. What motivates me to work in this field is the continuing challenge to understand biological systems and their emergent properties through better use of scientific data with computers and interdisciplinary technology applications. Main approaches that I employ include bioinformatics, in silico methods (databases, conceptual clustering, homology modeling, virtual screening, ontology and semantic analysis), functional genomics and proteomics applications along with traditional biochemistry, molecular biology, microbiology and cell biology techniques. My goal is to bring new insights into the evolutionary significance of metabolic adaptation, and construct phenotypic and process models that can be exploited in biotechnology and medicine.

Publications

Univalent Binding of the Cry1Ab Toxin of Bacillus thuringiensis to a Conserved Structural Motif in the Cadherin Receptor BT-R1. Biochemistry, 46 (35), 10001 -10007 (2007). 2007 - Publication

A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis. Proc. Natl. Acad. Sci., U S A. 103:9897-902 (2006). 2006 - Publication

Cytotoxicity of Bacillus thuringiensis Cry1Ab Toxln Depends on Specific Binding of Toxin to the Cadherin Receptor BT-R1 Expressed in Insect Cells. Cell Death Differ. 12, 1407-1416 (2005). 2005 - Publication

Selective antagonism to the cadherin BT-R1 interferes with calcium-induced adhesion of epithelial membrane vesicles. Biochemistry 43:1393-1400 (2004). 2004 - Publication

Expression of a midgut-specific cadherin BT-R1 during the development of Manduca sexta larva. Comp. Biochem. Physiol. 135:125-137 (2003). 2003 - Publication

Insect resistance to Bacillus thuringiensis: Alterations in the Indianmeal moth larval gut proteome. Mol. Cell Proteomics 2:19-28 (2003). 2003 - Publication

Proteclytic cleavage of the developmentally important cadherin BT-R1 in the midgut epithelium of Manduca sexta. Biochemistry, 47(41):13717-13724 (2002). 2002 - Publication

Cry1A toxins of Bacillus thuringiensis bind specifically to a region adjacent to the membrane-proximal extracellular domain of BT-R1 in Manduca sexta: involvement of a cadherin in the entomopathogenicity of Bacillus thuringiensis. Insect Biochem. Mol. Biol. 32, 1025-1036 (2002). 2002 - Publication

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Appointments

Professor
The University of Texas at Dallas [2006–Present]

Research Engineering Scientist
The University of Texas at Dallas [1999–2006]

Chief Science & Technology Officer
Biological Targets, Inc., Dallas, Texas [1999–2006]

Research Scientist
The University of Texas at Dallas [1997–1999]

Lead Scientist - Recombinant Vaccines
Cytoclonal Pharmaceutics, Inc., Dallas, TX [1995–1997]

Research and Teaching
Southern Methodist University [1989–1995]

Research
Middle East Technical University, Ankara, Turkey [1987–1989]

Research and Teaching Fellow - Medical Biology and Genetics
The University of Ankara Medical School, Ankara, Turkey [1986–1987]

Technical Associate - Clinical Biochemistry
Duzen Laboratories, Inc., Ankara, Turkey [1984–1986]

Projects

Targeting Phenotypic Adaptation for Antimicrobial Development

2004/05–2020/12 Virulence and resistance of bacterial pathogens during infection involve phenotypic adaptation in which pathogens modulate their metabolic activity in response to changing environment and nutrient availability in the host. This phenotypic adaptation is a survival strategy and allows pathogens to persist under severely-limited nutritional environments by utilizing molecules acquired from the host during infection.

During infection, under limited glucose availability in host, invading pathogens need to utilize metabolites arising from utilization of complex carbon sources like cholesterol, odd chain fatty acid, and certain amino acids as well as fermentation of various sugars. Effective inhibition of the production or the activity of certain enzymes abolishes key metabolic pathways in bacteria, resulting in significant reduction in bacterial growth and virulence expression, including biofilm production.

A novel antimicrobial target enzyme with classifiable substrate and catalytic function was identified, providing a promising approach for discovery of new anti-microbial, anti-infective, and anti-bacterial compounds as well as biofilm control agents.

University of Texas at Dallas
http://utdallas.technologypublisher.com/technology/28857

Characterization of enzyme active sites and potential ligand interactions through comparative modeling of protein three-dimensional structures.

2012/01–2020/11 University of Texas at Dallas
Undergraduate Research Program

Homology modeling and virtual screening of protein structure for potential ligand interactions.

2012/01–2020/10 University of Texas at Dallas
Undergraduate Research Program

Bioinformatics framework for conceptual mapping of relationships between folic acid and neural tube defects.

2011/08–2012/05 Information associated with genes and proteins are continuously increasing as high-throughput laboratory experimentation and massively-parallel computation methods facilitate faster data generation. However, accumulation of vast information and emergence of information silos pose a serious challenge to assimilation of information and effective analysis of functional correlations in biology and medicine. Thus extraction, integration and interpretation of information that is not coherently connected to each other, could help translating biomedical knowledge to practical applications.

Gene Ontology infrastructure has been described to facilitate semantic interoperability in mining, annotation, analysis, and integration of information about genes and proteins. These ontologies descibe attributes related to molecular function, cellular location and biological processes. We explored the utility of ontologies associated with neural tube folding and folic acid biology to find possible mechanistic relationship concerning folic acid deficiency and neural tube malformation. Results implicate the folate receptor 1 as a potential culprit in the formation of neural tube defects. Reduced folate transport may limit folate availability in developing embryo. We postulated that folate limitation may occur if the transport protein is down regulated as a result of excess folate supplementation, or the process may be limiting due to insufficient level and/or activity of the transport protein.

In addition, we show that conceptual mapping of gene-phenotype associations with GO is a useful approach to construct or validate a plausible hypothesis. The integrative and translational aspect of information re-use, as exploited in this study, could help reconcile disconnected information in the biomedical databases, and facilitate discovery of unrealized relationships. This could lead to applications critical to biomedical research and healthcare industry, including personalized medical treatments, pharmaceutical drug repositioning, bioinformatics and medical informatics

Structuring multidisciplinary biology courses - A case study: Cellular Microbiology.

2010/05–2010/05 University of Texas at Dallas

ASBMB Experimental Biology

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Additional Information

Teaching Activities

Biochemistry I (BIOL 3361) – Structures and chemical properties of amino acids; protein purification and characterization; protein structure; thermodynamics of protein folding; catalytic mechanisms, kinetics and regulation of enzymes; energetic of biochemical reactions; metabolism; roles of coenzymes and prosthetic groups; redox reactions; pathways for carbohydrate oxidation; glycogen metabolism; glucose synthesis; pentose phosphate pathway; electron transport and oxidative phosphorylation.

Biochemistry II (BIOL 3362) – Structure and functional properties of biological lipids (glycerolipids, phospholipids, ceramides, glycolipids, waxes, isoprene-based compounds, and steroids); physical and chemical properties of membranes; membrane organization and dynamics; membrane proteins and transport processes across cell membrane; regulation of lipid metabolism; biosynthesis, breakdown and interconversion of fatty acids, cholesterol, isoprenoids and eucosonoids; hormone action, organ specialization; integration of metabolism, metabolic disorders, and biochemical basis of certain pathological processes; nitrogen metabolism and fixation; nucleotide metabolism; structure and properties of nucleic acids; sequencing and genetic engineering; replication, transcription, and translation; chromosome structure.

Cellular Microbiology (BIOL 4310)– A unique study of infectious diseases in the context of ecological and evolutionary significance of symbiotic associations between microorganisms and human host. Dynamic equilibrium of human microbiome and how the composition and diversity of microbial communities inhabiting human body are involved in health and diseases. Introduction to the virulence and pathogenesis of various human pathogens with up-to-date focus on molecular and cellular aspects of host responses. Topics include evolution of pathogen, invasion and subversion strategies of bacterial pathogens, toxins and secretion mechanisms, manipulation of host defenses and cell death, inflammation, sepsis, and advances in microbiome research. Particular attention is given to current trends in translational medicine that evaluate the symbiotic relationships between humans and gut microbiome and establishes new paradigms on how variations in the microbiome influence human health, metabolism and behavior.

Nutrition and Metabolism (BIOL 4325) - Nutrient utilization and requirements with an emphasis on multifaceted links between diet, health, genetics, microbiome, and diseases. Basis of nutritional physiological phenomena and metabolic hemostasis in the context of human development, aging, exercise, health and diseases. Integration of energy metabolism and physiological requirements concerning macronutrients and major vitamins and minerals as well as benefits of potentially-protective compounds in food. How unbalanced intake of nutrients contributes to the initiation, development and severity of various chronic diseases, including coronary heart disease, atherosclerosis, lipidemia, hypertension, diabetes, obesity, osteoporosis, thyroid disorders, immune dysfunction, inflammatory conditions, cancer, and dysbiosis are discussed with relevance to clinical nutrition. Nutritional characteristics of diets are examined in the context of human evolution and behavioral, societal and ecological interactions. Interconnected problems involving public health, sustainable food, nutrition security, agriculture and the food industry are discussed. The course also introduces microbiomics, nutrigenomics, nutrigenetics and chrononutrition to explore evolving concepts concerning gene-nutrient interactions, particularly the influence of diet on intestinal microbiota and the effect of sleep on metabolism.

Biotechnology Laboratory (BIOL 6684) – Applications of biotechnology methods in a laboratory setting; isolation and analysis of DNA, proteomics (theories and concepts related to research and clinical studies, 1D and 2D SDS PAGE, liquid chromatography, instrumentation basics of mass spectrometry, ionization techniques, peptide fragmentation, peptide fingerprinting, and protein identification and bioinformatics applications for protein sequence analysis and BLAST Searching), real time PCR, ELISA, FACS cell sorting, transfection of animal cells, immunocytochemistry and confocal microscopy.

BIOL 6V51 - Biotechnology Project Design: The course engages students to design a theoretical application that addresses a problem or need with a biotechnological solution. It aims to build students’ multidisciplinary knowledge and integrative skills with case-based learning. The central theme is development of a self-guided project in which students propose conception of inventive and visionary products. The projects may involve applications concerning medicine, agriculture, energy, or the environment, such as therapeutic drugs and biologicals to treat diseases and disorders, bioanalytical applications with mechanical and electronic adaptations for measuring biological markers, genetically modified plants with enhanced traits for increasing food and feed production, metabolic engineering approaches to design microbes for production of biofuels and industrial biochemicals, or ecosystem bioremediation, etc. Projects are expected to combine theoretical concepts and practical approaches within a multistage decision-making process in which ideas are modeled towards application development. Projects are evaluated from procedural, integrative, and organizational perspectives. Emphasis is given on problem definition, scientific valuation, simplicity and specificity of the approach, and real-life application potential. Assessment is done critically at three levels: to monitor students’ progress, to check completion of specific points that describe the approach-goal-motivation-scope, and to evaluate final report. Report should include work that substantiates comprehension of the background information, knowledge and use of gene/protein sequences and structures, molecular and cellular processes, scientific methodology, application design and/or process development. The course is appropriate for students interested in applying engineering principles to develop comprehensive and multidimensional hypothetical approaches.

Eukaryotic Molecular Cell Biology (BIOL 3302) – Structural organization of eukaryotic cells; regulation of cellular activities; membranes and transport across cell membrane; cell specialization; cell signaling molecules and cell surface receptors; signal transduction pathways that control gene activity; the organization and control of the eukaryotic cytoskeleton; mechanisms of protein targeting to cellular organelles; vesicle traffic, secretion and endocytosis; the molecular regulation of the eukaryotic cell cycle, and aspects of the molecular basis of cancer.
Independent Study - Research and Advanced Writing (BIOL 4390) – Planning and conducting thematic research; strategies for scientific literature analysis, examining original research articles, communicating facts and theories by coherent writing.

Modern Biology I (BIOL 2311) – Fundamental concepts in modern biology with an emphasis on molecular and cellular basis of biological phenomena. Topics include the basic biochemistry of biological molecules; cellular metabolism, organization of prokaryotic and eukaryotic cells, introductory classical and molecular genetics, essentials of mammalian physiology, organizational and operation principles of endocrine, immune, and nervous systems, and selected aspects of developmental biology, as well as study of major groups of biological organisms such as bacteria, viruses and fungi.

Modern Biology II (BIOL 2312) – Fundamental aspects of mammalian physiology with an emphasis on the human body systems, physiological evolution, organ development, regulation of organ functions and physiological mechanisms regulating the internal environment (homeostasis).

Natural Science & Mathematics Freshmen Seminar (NATS1101) – An overview of approaches to basic study and learning strategies, critical thinking, problem solving, group work and other skills as well as studentship and professional ethics; inter-disciplinary and cross-disciplinary connections within the programs of the School of Natural Science and Mathematics as well as their relationship to other scientific, technology and engineering fields and interdisciplinary applications. Emphasis is given to discussions on current and emerging themes of scientific research, education and technology applications in the 21st century.
Cell and Molecular Biology Laboratory (BIOL 4380)– DNA manipulation, cloning, bacterial transformation, plasmid mapping, PCR, DNA fingerprinting, mutagenesis and AMES test, centrifugation, cell fractionation, enzyme assays, mammalian cell culture techniques, transfection and ion-trapping

Body Systems (BIOL 1300) – Introductory to human physiology in relation to molecular, cellular and anatomical structures; examination of human body and organ systems with model-based lab exercises; physiological functions associated with homeostasis and integration of metabolism, basic information about diseases and disorders with special considerations to preventative and self-care approaches.

Introduction to Biotechnology (BIOL 5V00)– overview of techniques utilized in biomedical research and bioprocessing/biomanufacturing applications in the pharmaceutical, agricultural and environmental biotechnology industries; principles of common methods involving protein chemistry, molecular and cell biology; macromolecular separation, purification and analysis of biological molecules, chromatography, electrophoresis, molecular and cellular labeling, detection and assay methods, use of antibodies, DNA sequencing, recombinant DNA, protein engineering, nucleic acid primers, amplification and hybridization-based methods, PCR, RT-PCR, qPCR, gene libraries, genotyping, gene expression analysis, microarrays, bioinformatics, genomics, proteomics, DIGE, ICAT, mass spectroscopy, and systems biology-based approaches; molecular diagnostics, biomarkers and clinical trials

Biology of Aging – (under development): concepts and theories of aging; the evolution and genetics of aging; oxidative processes in aging; nutritional and physiological aspects of aging and longevity; mammalian metabolism in aging; dietary restriction, health and longevity; effect of age on gene expression; instability of the nuclear genome and alterations of the mitochondrial genome during aging; cell proliferation in mammalian aging; pathophysiology of aging and age-related diseases.

Activities

Affiliations

Current

ASBMB - American Society for Biochemistry and Molecular Biology

Sigma Xi Scientific Research Honors Society

National Center for Case Study Teaching in Science

The Retina Foundation of the Southwest

Past

Board for Knowledge, Southern Methodist University (Dallas, TX)
Medical Technology Program Board, UT Southwestern Medical School (Dallas, TX)
Association of Clinical Research Professionals (Alexandria, VA)
American Association for Advancement of Science (Washington, DC)
American Chemical Society (Washington, DC)
Society of Industrial Microbiology (Fairfax, VA)
New York Academy of Sciences (New York, NY)
American Society for Microbiology (Washington, DC) American Society for Tropical Medicine (Northbrook, IL)