Biochemistry & Molecular Biology

Dr. Patricia Canaan received her B.S. degree in Medical Technology in 1986 at Oklahoma State University. She obtained her M.S. degree in 1990 in Microbiology and her Ph.D. degree in Microbiology and Molecular Genetics in 1997 at Oklahoma State University, Stillwater OK. Dr. Canaan then joined the department of Microbiology and Molecular Genetics at Oklahoma State University in the research lab led by Dr. Rolf Prade investigated the genetics of plant cell wall breakdown by filamentous fungi including Aspergillus nidulans as a model system. In 2001, Dr. Canaan joined the Department of Biochemistry and Molecular Biology, Oklahoma State University, where she served as Assistant Director of the OSU Microarray Core Facility. In 2004, Dr. Canaan joined the faculty at the Department of Biochemistry and Molecular Biology, Oklahoma State University, where she plays an important role in undergraduate teaching and academic advising. Dr. Canaan has developed a research program focused on antibiotic resistance in Elizabethkingia.

Research Interests:

The Canaan lab uses advanced technologies and genomics approaches including metagenomic and proteomic approaches, genome sequence analysis, transcriptomics, DNA microarray analysis and various bioinformatics tools to study a variety of biological problems. Studies have include intracellular parasitic modulation of gene expression in human host cells by Anaplasma phagocytophilum (de la Fuente 2008 and Galindo 2008) or Coxiella burnetii (Mahapatra 2010), specific induction and relief from carbon catabolite repression as two systems involved in expression of genes for metabolism of complex polysaccharides; and gene expression patterns during carbon deprivation and pectin metabolism by the filamentous fungus Aspergillus nidulans (Ray 2011 and Saykhedkar 2011) or Phanerochaete chrysosporium (Ray 2011). Bioinformatics tools such as PipeOnLine and GenePix Auto-Processor have been developed to assist in automated processing of large-scale biological data. PipeOnline is a web-based integration of tools designed to process DNA sequence data and generate online pubic and private databases (Ayoubi 2001). GenePix Auto-Processor (GPAP) is a web-based interface for second level preprocessing and statistical analysis of primary expression data obtained from microarray image processing (Weng 2005). More recently, Dr. Canaan's lab is interested in metagenomic and proteomic approaches to identify candidate enzymes to identify novel genes and enzymes in bacteria useful for lignocellulose bioconversion (Dalvi 2011 and Prabhakaran 2011). Tools, algorithms and robust computational resources for rapid pre-processing and annotation of metagomic-scale sequence data are vital to these studies.

I am a quantitative and computational geneticist by training. As a faculty member, I am currently leading a team that primarily focuses on data-driven statistical and learning approaches for discovery, forecast, and predictive diagnostics. Our general research interests revolve around understand the intricate interplay between biotic and abiotic forces that shape the complexity of our world.

At Chen's Crop Genomics laboratory, we leverage the advancement in genomics and computational technologies to delve into how nature, including biological beings and the ecosystems, natural and managed, adapts to adversity and evolves. More importantly, our pursuits extend beyond mere discovery. We are driven by the conviction that advancing knowledge is integral to fostering promising applications in agriculture and natural resource conservation for a sustainable future.

Research Interests:

The speed, cost and accessibility of DNA sequencing has been transformed in recent years by new technologies, opening up exciting opportunities for disease diagnosis, therapeutic intervention and studying complex trait variations. Chief among these is genome wide association studies, frequently referred as GWAS, where researchers look for SNP genetic polymorphisms that give raise to phenotypic variation or are in linkage disequilibrium with the causative genetic variants. To further annotate the effect of these associations on phenotypes, researchers often take route of searching and collecting relevant information from literatures, public resources and databases, seeking supporting evidence that pillars the peaks of these significant associations.

Working closely with omics research groups here at OSU, we are setting off to connect the dots, by integrating analyses at different omic molecular phenotypes to examine one of the basic biological principle: DNA -> RNA -> proteins/pathways -> phenotypes. As more genomic sequences and functional data becoming available, in Chen's research laboratory we propose that computational, functional predictions would be accelerating discovery by turning wisdom of crowds into testable hypotheses.

In addition, the rich, multidimensional genomic knowledge invites agriculture sectors to use whole-genome approaches to improve efficiency of variety development programs. Oklahoma dual-purpose wheat varieties play a vital role in both yield production and cattle industry in the US. However, wheat variety development is so far centered on creating genetically stable, pure-line genotypes that could be reached by decade-long, resource-dependent endeavor, involving sustained institutional commitment. More over, while successful, the traditional means of variety development are technologically and spatially static, unless extensive territories are spent on expansive phenotype assessment.

To advance technologies used to foster Oklahoma's largest cash crop, we also coordinate advancement in genomics and quantitative genetics with breeding efforts of OSU's Wheat Improvement Team. We are currently investigating means to optimize applicability and efficiency of genomics-enabled selection (genomic prediction), aiming to translate genomic knowledge to genetic gain in wheat field through technological and computational advancement.

Dr. Yong Cheng received his B.S. degree in Biotechnology in 2002 and his Ph.D. degree in Microbiology in 2007 from Huazhong Agricultural University, China. In 2007, Dr. Cheng joined the University of Basel, Switzerland, with F. Hoffmann–La Roche Ltd Postdoctoral Fellowship. In 2011, Dr. Cheng then joined the Dr. Jeffrey Schorey's lab at the University of Notre Dame, Indiana. Dr. Cheng's previous study focused on the research understanding the mechanism of host-pathogen interactions in the context of mycobacterial infections, and novel antimycobacterial drug discovery in collaboration with the biopharmaceutical companies, Hsiri Therapeutics Inc and Shionogi & Co. His study also included the development of new anti-tuberculosis vaccines and diagnostic tools. In 2020, Dr. Cheng joined the Department of Biochemistry and Molecular Biology, Oklahoma State University. He is currently working on multiple projects understanding the interactions between Mycobacterium tuberculosis/non-tuberculous mycobacteria (NTM) and the host.

Research Interests:

Our research is focused on understanding the molecular and cellular mechanisms of the host-pathogen interactions during mycobacterial infections. 1) Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has infected one third of populations across the world, leading to 9 million new TB cases and 1.4 million deaths annually. Among those infected, 5 - 10% people would develop active TB disease during their lifetime. While the development of novel technologies such as diagnostic platforms advanced the global TB control in the past decades, TB remains one of the most fatal infectious diseases. 2) Nontuberculous Mycobacteria, including Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex, are emerging pathogens that are responsible for severe lung infections in individuals suffering from bronchiectasis, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. The mechanism on how mycobacterial infection leads to the disease remains to be elucidated. The long-term goal of our research is to decipher the mechanisms of mycobacterial pathogenesis and the host defense to these organisms using cutting-edge technologies. We hope that our research will facilitate the development of novel, active and cost-effective antimycobacterial drugs and vaccines.

We are always looking for motivated students. If you are interested in our projects, please contact us

Dr. Junpeng Deng received his B.S. degree in 1993 from University of Science and Technology of China. He obtained his M.S. degree in 1996 from Institute of Biophysics, Chinese Academy of Sciences. In 2001, he obtained his Ph.D. degree in Biophysics at the Ohio State University, Columbus OH. Dr. Deng then joined Howard Hughes Medical Institute at the site of Seattle, Washington in 2001, in the research lab led by Dr. Wim HOL who is a pioneer in protein crystallography and structure based drug design. In 2006, Dr. Deng joined the faculty at the Department of Biochemistry and Molecular Biology, Oklahoma State University, where he plays a leading role in protein structural biology. Dr. Deng has developed a vigorous research program, focusing on essential proteins related to Parkinson's disease,cytokine signaling, autoimmune and infectious diseases.

Research Interests:

In this lab, we are interested in understanding the structure and function of proteins that are involved in important biological pathways. We are using biochemical and biophysical approaches such as x-ray crystallography to investigate the mechanisms by which these protein molecules function and how they are related to human diseases such as neurodegenerative diseases, autoimmune and inflammatory diseases, infectious diseases and cancer.

Feng obtained his Ph.D. in 2012 from Tsinghua University in China. His Ph.D. project studied how bacterial effector proteins regulate plant immunity and discovered a new biochemical mechanism by which bacterial pathogens battle plant immune system. He then continued working on plant immunity as a Research Associate at Dr. Jian-Min Zhou's Lab at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Following the work on plant immunity, he chose to spend his postdoctoral research on plant symbiosis and joined the group of Dr. Giles Oldroyd at the John Innes Centre (from 2013 to 2017) and University of Cambridge (from 2017 to 2020). He was particularly interested in understanding how plant recognizes signaling molecules produced by beneficial microbes to establish symbiosis. He started his independent research career in August 2020 as an Assistant Professor in the Department of Biochemistry and Molecular Biology, Oklahoma State University. His research aims to understand how and why plants engage with their rhizosphere communities in response to the diverse environmental conditions.

Research Interests:

Plant roots are associated with innumerable microorganisms including both pathogens and beneficial symbionts. Pathogens restrict plant growth by diverting resources and releasing toxins, in contrast, symbionts promote plant growth through increasing nutrient availability. Plants therefore must make the decision to either promote or inhibit the growth of microbes they encounter. In most plants two different signaling pathways act to decide the appropriate response, the immune signaling pathway which restricts microbial colonization, and the symbiosis signaling pathway which facilitates microbial colonization. Our research demonstrated that the environmental condition of the plant plays a very important role in informing the plant's decision through regulating the dynamic interplay between immunity and symbiosis pathways. We are currently using a combination of molecular, cell biology, genetic and biochemical approaches to explore how the different abiotic environmental factors regulate plant-microbe interactions and how plant immunity and symbiosis signaling pathways affect the broader microbial community. Our research will inform the design of novel cropping systems that support crops with improved capacities to extract nutrients from their environments to reduce chemical fertilizer use, ward off diseases and thrive in the face of climate change.

We are recruiting Ph.D. students and Postdocs. If you are interested in our research, please contact Dr. Feng with your CV and a brief statement of your research interests. If you are undergraduate student and would like to spend your time on research project, welcome to join us!

I received my B.Sc. and M.S. from the Department of Biological Sciences at Illinois State University (Brian J. Wilkinson's laboratory) and then completed my Ph.D. at the Institute for Medical Microbiology at the University of Zurich, Switzerland (Brigitte Berger-Bachi's laboratory).I then went on to serve as a postdoctoral fellow in the Department of Molecular Biology and Microbiology at Tufts University School of Medicine (Stuart B. Levy's laboratory). At New Mexico State University in Las Cruces I served as the Director of the NMSU graduate program in Molecular Biology, as the Associate Department Head of Biology,and as the Biology Department Head. I also served two years on the faculty of the Chicago College of Osteopathic Medicine at Midwestern University and I began my academic career at the School of Biomedical Sciences at Curtin University of Technology in Perth Western Australia. I adore hanging out with family,friends, and loved ones, cannot imagine a life without dogs, and am amazed by all living creatures (everyone should be!), from single-celled organisms on up.I do everything I can to get people excited about the importance of scientific evidence and the incredible wonder of evolution– "the greatest show on earth".

Research Interests:

I am an expert on bacterial antimicrobial resistance who presently serves as Professor and Department Head of the Biochemistry and Molecular Biology Department. Staphylococcus aureus is responsible for ~ 19,000 deaths each year in the United States and the ability of this organism to acquire antimicrobial resistance is almost unmatched in the bacterial world. One effective method to prevent the spread of S. aureus is by using appropriate hand-disinfection which includes the use of alcohol-based hand rubs. One of the projects my laboratory is currently working on attempts to determine how S. aureus responds to antiseptics like alcohol and how this organism evolves to thwart the action of antiseptics. We have also recently begun investigating antimicrobial resistance mechanisms in the Elizabethkinigia which are emerging pathogens. These organisms cause serious infections (e.g. meningitis) in neonates, immunocompromised individuals, and the elderly, and cause community and hospital infection outbreaks. The Elizabethkingia express multiple antimicrobial resistance, which makes it difficult to find antimicrobials to treat infections caused by these organisms. I have trained a large number of undergraduate researchers in a biological safety level 2 laboratory, and have graduated numerous successful Masters and Ph.D students.

I graduated from OSU in 1966 with a BS in Microbiology. I became a laboratory technician in the laboratory of Dr. Odell. He encouraged me to pursue a Master's degree. I graduated with a Master's degree in Biochemistry in 1970. I became the Instructor for Biochemistry and Molecular Biology graduate and undergraduate laboratories in January 1970. I enjoy giving students the ability to pursue a career in medicine, scientific research, or chemical analysis.

My training in medicine (M.D.) has fostered a strong interest in understanding disease pathogenesis, particularly from the perspective of molecular therapeutics. To fuel this interest, I pursued a Ph.D. in biochemistry and molecular biology, undertaking a project related to diabetic retinopathy. This work yielded important insight on the non-conventional anti-inflammatory effect of erythropoietin on Müller cells. During my subsequent brief postdoctoral training in Dr. Weijun Jin's lab at SUNY Downstate Medical Center, I demonstrated the protective effect of the furin prodomain in atherosclerosis. Through these two projects, I cemented my interest in health outcomes related to metabolic disorders. I joined Dr. Guang William Wong's lab at Johns Hopkins University School of Medicine to acquire additional skills and expertise on molecular, genetic and physiological aspects of metabolism. I have now characterized the roles of 6 of the 15C1q/TNF-Related Proteins (CTRPs) in glucose and lipid metabolism using type 2 diabetes mousemodels. I joined the Department of Biochemistry and MolecularBiology at OSU in July 2019. My lab focuses on investigating the metabolic regulation of CTRP family members in physiology and disease.

Research Interests:

C1q/TNF-Related Proteins (CTRPs) are a conserved family of 15 secreted proteins that function in glucose and lipid metabolism. Metabolism and immunity are linked by proteins with dual functions such as the CTRP family proteins. One of my postdoctoral projects focused on understanding how the CTRP6 protein links obesity to adipose tissue inflammation. In obese and diabetic humans and mouse models, I found that CTRP6 expression was markedly upregulated in adipose tissue. Mechanistically, CTRP6 regulates local inflammation and glucose metabolism by targeting adipose tissue macrophages and adipocytes, respectively. I provide the first physiological evidence, using gain- and loss-of function mouse models, that CTRP6 is a novel secreted regulator of systemic glucose metabolism through both autocrine and paracrine action, which modulates insulin sensitivity and pro-inflammatory responses within adipose tissue. My long-term goal is to understand the underlying molecular and cellular mechanisms of immunometabolic regulation by CTRPs and their receptors and other secreted proteins and their receptors. Secreted and transmembrane proteins have advanced properties that lend themselves to be utilized as therapeutic agents or targets. My lab will exploit genetic mouse models, cellular and molecular techniques, histological assays, flow cytometry, and gene expression profiling methods (e.g., RNA-seq) and metabolomics to study protein function in immunometabolism. I believe our findings will greatly contribute to the development of new potential therapeutic targets for the treatment of obesity and diabetes.

Dr. Ashley Mattison is an Assistant Professor in the Biochemistry and Molecular Biology Department at Oklahoma State University. She currently teaches Survey of Biochemistry, Biochemistry and Molecular Biology Laboratory, and Fundamentals of Biochemistry. Her research/extension work focuses on K-12 STEM education.

BIO

I received my Bachelor's degree in Agriculture at the University of Agricultural Sciences, Bangalore (India), Master's degree in Horticulture at Clemson University and Ph.D. in Genetics at Purdue University. I did my postdoctoral training in plant genomics at the Boyce Thompson Institute for Plant Research, Cornell University with Dr. Greg Martin. After my postdoctoral training, I joined Noble Research Institute as an Assistant Professor in 2002 and rose up to the rank of Full Professor. Later I served as the head of Plant, Microbe and Soil Section at the Noble Research Institute for three years before joining Oklahoma State University as a Research Professor in 2021. My research interests center on molecular plant-microbe interactions, abiotic stress tolerance, and plant genetic resource development. I have authored over 250 peer-reviewed manuscripts in international journals. I am an elected fellow of the American Association for the Advancement of Science (AAAS). I am the recipient of Fulbright-Nehru Academic & Professional Excellence Award and Ruth Allen award from the American Phytopathological Society (APS). I serve on the editorial boards of peer reviewed journals, BMC Plant Biology, Bioenergy Research, PeerJ and Grassland Research.

Research Interests:

Many projects in my lab focus on Molecular-Plant Microbe Interactions. One of the main projects in this area is to understand the phenomenon of nonhost disease resistance. Nonhost resistance is the most common form of disease resistance exhibited by plants against the majority of potentially pathogenic microorganisms. Nonhost resistance has been a topic of interest for many plant pathology researchers for several years. Despite tremendous progress in molecular plant pathology, nonhost resistance is still poorly understood in contrast with classical gene-for-gene resistance. Nicotiana benthamiana and Medicago truncatula are being used as model plants to understand nonhost resistance mechanisms. Virus-induced gene silencing (VIGS) based fast-forward genetics in N. benthamiana is being used to identify plant genes that play a role in nonhost resistance against both bacterial and fungal pathogens. Transposon insertion mutants of M. truncatula are also being used to screen for mutants that compromise nonhost resistance against Asian soybean rust. This study will help better understand how plants defend against pathogens and to genetically engineer crop plants for broad resistance. Interestingly, some of the genes identified to play a role in nonhost disease resistance also plays a role in abiotic stresses such as drought and heat. Some projects in my lab also focus on abiotic stress tolerance in a hope to engineer multi-stress tolerant plants.
Another project in my lab focuses on understanding Agrobacterium-mediated plant transformation. Genetic transformation of plant cells by Agrobacterium tumefaciens represents a unique case of trans-kingdom sex requiring the involvement of both bacterial virulence proteins and plant-encoded proteins. We are identifying plant genes that play a role in Agrobacterium-mediated plant transformation that can help increase the transformation efficiency of transformation-recalcitrant crops like soybean and wheat and to prevent crown gall disease in horticultural crops. To increase plant transformation efficiency in recalcitrant crop varieties, we have engineered an Agrobacterium strain that can express a Type III secretion system to deliver proteins that can enhance transformation.
My lab has developed a large collection of transposon insertion mutants in M. truncatula using a tobacco retrotransposon, Tnt1, which is a viable and attractive option to introduce multiple independent insertions per plant for saturation mutagenesis. More than 20,000 transposon tagged M. truncatula lines encompassing more than one million insertions have already been developed and is available to the scientific community. A flanking sequence tag (FST) database with more than 400,000 FSTs has been created and can be used for BLAST searches (https://medicago-mutant.dasnr.okstate.edu/mutant/blast/blast.php) to identify M. truncatula mutant(s) in the gene of interest.

Dr. Ruhl is an Associate Professor in the Department of Biochemistry and Molecular Biology and researches the impact of chromatin structure on epigenetic regulation as it relates to organisms and disease. After obtaining a degree in Chemistry from the University of Missouri – St. Louis he attended graduate school at Saint Louis University School of Medicine where he joined the laboratory of Dr. John Chrivia and studied the mechanism of transcriptional regulation mediated by the estrogen receptor and the hormone estrogen. This process is of biological interest due to its link to breast cancer. After receiving a PhD in Pharmacology and Physiology, he joined the laboratory of Dr. W. Lee Kraus at Cornell University where he did his postdoctoral work. As a postdoctoral fellow, he studied the biophysical and biochemical regulation of chromatin structure in response to the estrogen receptor-estrogen complex. He joined Oklahoma State University in 2010.

Research Interests:

In the Ruhl lab, we are interested in understanding how DNA, the molecular blueprint of an organism, is properly read and maintained. Errors in this process lead to disease, most notably cancers. Although a broad range of proteins are involved in this process, we are interested in the Swi/Snf chromatin remodeling complex due to the presence of several tumor suppressors. Using a variety of biochemical and cell-based approaches, we seek knowledge into the link between Swi/Snf function and cancer development. Insight into these processes will aid in the intelligent design of therapeutic drugs that target tumors arising from aberrations in Swi/Snf function. Epigenomic information defines unique patterns of gene expression to maintain cellular identity in an organism. Research into epigenetic mechanisms, including DNA methylation, nucleosome positioning, histone modifications and histone variant deposition, has identified aberrations within these programs that contribute alterations in gene expression that can manifest as an oncogenic phenotype, i.e. a change in cellular identity. Of particular interest is the molecular mechanisms of ATP-dependent remodeling complexes in the accurate positioning of nucleosomes to further understand causality in cancers and aid in the expansion of treatment options. Through the application of biochemical, cell based and genomic approaches in mammalian-based systems, I am interested in understanding the process of nucleosome positioning in both the normal and diseased states.

After obtaining B.Sc. in Biology from Sri Venkateswara University, I pursued M.Sc. and Ph.D. in Botany from Sri Krishnadevarya University, India. I have conducted postdoctoral research at the Weizmann Institute of Science, Israel (Dr. Hillel Fromm), University of Bonn, Germany (Dr. Dorothea Bartels) and University of California, Riverside (Dr. Jian-Kang Zhu, a Member of the U.S. National Academy of Sciences). I joined the Department of Biochemistry and Molecular Biology, Oklahoma State University as an Assistant Professor in 2006, and promoted to Associate Professor in 2011, and Professor in 2016. I have edited 1st and 2nd editions of Plant Stress Tolerance: Methods and Protocols under the series of Methods in Molecular Biology, and a book entitled "MicroRNAs in Plant Development and Stress Responses". I served as an associate/handling editor for peer-reviewed journals such as Molecular Biotechnology, BMC Plant Biology, BMC Genomics, and Journal of Experimental Botany.

Research Interests:

The transcription of a gene depends not only on the DNA sequence and availability of sequence-specific regulatory factors (transcription factors) but also on the presentation of genes within the complex architecture of the chromosome. Epigenetic modifications (DNA methylation and histone modifications) are known to regulate gene expression by bringing changes in the chromatin state. For instance, methylation at position 5 of cytosines is a major epigenetic modification of genomic DNA, which is frequently associated with silencing gene expression. Similarly, histone modifications such as the methylation/acetylation at specific amino acids has the code for gene expression or silencing. Thus, epigenetic modifications have an essential role in regulating genes, dictating when and where they should be expressed or silenced. Our research is directed to identify specific epigenomic changes that contribute to gene expression/silencing during stress. We are using use genome-wide analysis of cytosine methylation and chromatin immunoprecipitation (ChIP) to identify such epigenetic changes. This knowledge will provide basis for transcriptional gene regulation that is critical for plant survival under stressful conditions.



The microRNAs regulate when, where and how much of a protein needs to be made by degrading certain number of the mRNA molecules of specific genes while leaving the rest for protein production. In other words, microRNAs serve as quantity controllers of protein production, as such understanding microRNA-guided gene regulation broadens our knowledge about posttranscriptional gene regulation. In an effort to identify the role of miRNA-guided gene regulation in response to abiotic stress conditions, we use high-throughput sequencing of small RNAs and their mRNA targets that are cleaved. Overall, our fundamental research can help unravel complex molecular networks that underlie plant stress tolerance mechanisms.

I am currently an associate professor of biochemistry and adjunct professor of microbiology at Oklahoma State University. As one of Oklahoma's three major universities, OSU is located in the pleasant town of Stillwater, near the geographic center of America. Here, I teach biochemistry to large classes of undergraduate students. I also lead a vigorous research program on antibiotics and bacterial translation mechanisms. Finally, I help to advise students through their course curricula and research toward their bachelor and doctoral degrees at OSU, and their career choices beyond that. I am challenged by all three jobs. I am thrilled to be surrounded by enthusiastic and congenial students, professors, and administrators, who are proud to call OSU "America's brightest orange".

How I ended up at OSU involved a long and circuitous journey, which I will tell briefly. I grew up in south Florida, near swampland of the Everglades. As a young boy in the 1970s, I became passionately interested in swamp life, particularly birds, and I envisioned becoming an ornithologist as an adult. As I grew older, my interests shifted toward biochemistry because I wanted to understand the molecular foundations of all life forms. An outstanding chemistry teacher, Helen Reynolds, sparked my interest in biochemistry when I was a student at Jupiter High School.

In 1984, I began my undergraduate studies at the University of Florida. Since they did not offer a bachelor degree in biochemistry, I transferred to the University of Arizona. In my senior year, I became excited by genetic engineering technologies that were being developed in bacterial cells – harmless lab strains of Escherichia coli. My first research project, under the direction of Professor John Little, focused on gene expression in E. coli viruses. I took advantage of new techniques for engineering DNA molecules, the polymerase chain reaction (PCR) and site-directed mutagenesis (Mullis & Smith, 1993), which later proved valuable in my doctoral research. This experience convinced me to continue research on the Central Dogma of gene expression: DNA Replication -> Transcription -> Translation.

In 1988, I moved to the University of Oregon to pursue graduate studies under the direction of Professor Peter von Hippel. He is a pioneer of biophysical chemistry, especially protein enzymes that catalyze DNA replication and transcription. My doctoral research focused on transcription catalyzed by the central enzyme RNA polymerase purified from E. coli. I examined the formation of hairpin structures in the RNA synthesized by the polymerase, and analyzed the effects of RNA hairpins on the thermodynamic stability of transcription complexes.

During my graduate studies, I became excited by the discovery of ribozymes (enzymes composed of RNA). Their discovery solved a major conundrum: How could nucleic acids serve as both hereditary material and catalysts in the first living cells on Earth? In modern cells, the most sophisticated ribozyme is the ribosome, whose ribosomal RNA molecules catalyze the translation step of gene expression. Many modern viruses carry RNA hereditary material, such as those causing AIDS or flu in humans.

After earning my Ph.D. in 1995, I decided to continue research along the pathway of the Central Dogma, and study the biochemistry of translation in E coli. I moved to the University of California at Santa Cruz, where I conducted postdoctoral research under the direction of Professor Harry Noller. He is one of the most prominent scientists studying ribosomes and one of the first to propose that the ribosomal RNA catalyzes the formation of peptide bonds between amino acids during the synthesis of proteins in the process of translation. My postdoctoral work lead us to groundbreaking insights into how translation is regulated by unusual proteins that mimic the shape transfer RNAs, which carry amino acids to the ribosome during translation. While this work was in progress, I was extraordinarily fortunate to witness truly groundbreaking research that led to atomic structures of the ribosome for the first time. The first crystal structure of a fully assembled bacterial ribosome was determined by my postdoctoral colleagues in Noller's lab. Along with atomic structures of the ribosome's subunits determined in three independent labs, this work revolutionized our understanding of translation and was eventually recognized by a Nobel prize in 2009.

I landed my first appointment as an assistant professor at the University of Alberta in Western Canada. I remember bravely moving to the Cold White North in January 2001. My first winter was a harsh adjustment in more ways than one. I experienced temperatures of -40 (same number, Celsius or Fahrenheit scales!) for the first time in my life. I found a stark beauty in seeing the Northern Lights above the city of Edmonton, as well as the rugged Canadian Rockies. While adjusting to life in Canada, I also faced the challenge of building my independent research lab.

My continued research on bacterial ribosomes offered many exciting avenues, but changed my perspective, in light of the ribosome structures. Since my lab was in a medical school and I needed grant money, my research progressively shifted toward antibiotics, which commonly target ribosomes in pathogenic bacteria. This shift was greatly facilitated through my collaboration with Professor Diane Taylor, along with help of graduate and postdoctoral students in my lab. My connections with other professors in the international RNA Society, as well as RiboWest and RiboClub of Canada, would later prove valuable to me.

We had a productive lab and published several notable research papers over the next several years. We deciphered the mechanisms of GTP hydrolytic proteins and antibiotics that regulate translation. However, because my position required me to procure my external salary, I faced unexpected financial difficulties by 2010. Fortunately, after graduating my students, I was able to move to McGill University in Montreal, where I spent a sabbatical year in Professor Nahum Sonenberg's lab. During that year, I was strategically planning to land a permanent position, preferably in Montreal, but also searched widely across North America.

As many of my academic colleagues know, our profession can often be unpredictable. So for me in 2011, I was invited to interview at OSU and offered the position that I currently hold. I had not been to Oklahoma before that time, and I was pleasantly surprised by what I found here. Although Oklahoma's weather is unpredictable and inhospitable at times, the wonderful people of this university make this a great place to be. We have a vibrant community of professors and students in our department. It is a wonderful time to be at OSU!

Research Interests:

Antibiotics are some of our most powerful and valued drugs, virtually eradicating previously dreaded diseases such as scarlet fever, tuberculosis, and bubonic plague. Ironically, only a few new antibiotics have been introduced since the 1960s. A crisis looms on the horizon with old antibiotics losing their effectiveness due to the rise of multidrug-resistant bacteria, chronic infections, and immune-compromised patients. Resistance arises from two primary sources: from bacteria harboring mobile resistance genes that can be spread to other cells; and from 'persister cells', which are dormant variants of regular bacteria that are highly tolerant to antibiotics. The rise in resistance is exacerbated by our ubiquitous use of antibiotics in everything from medicine to agriculture. Furthermore, antibiotics indiscriminately attack harmful and helpful bacteria in our gastrointestinal tracts and societies.

Antibiotics from natural sources (plants, fungi, and other bacteria) commonly target bacterial ribosomes, which translate mRNAs into proteins. This translational machinery is also a source for acquiring resistance to antibiotics. The highly conserved nature of this machinery facilitates our broad use of antibiotics, yet it also promotes resistance in bacterial populations. Translation and antibiotics are inextricably connected to bacterial physiology, growth and multiplication. Yet there is a significant lack of information about how ribosome-targeting antibiotics alter bacterial physiology.

To begin to fill this void, my lab is investigating how antibiotics perturb the translational machinery in bacterial cells. Using novel methodology, we are purifying the full translational machinery from both harmful and helpful bacteria. We are quantitatively assessing the components of this machinery and other putative factors connecting it to bacterial physiology. We are comparing the effects of antibiotics on the composition and dynamics of the translational machinery. These studies will reveal how antibiotics that target the ribosome dismantle bacterial physiology, leading to bacterial death. These insights will be a critical prerequisite for the development of new more effective and specific antibiotics. And they prepare us for the new more deadly drug-resistant bacteria that will most assuredly arise in the future.