Andrew Annalora | Department of Environmental & Molecular Toxicology
In the vast landscape of scientific exploration, there are individuals whose dedication to unraveling the mysteries of biology leads them on remarkable journeys. One such individual is a scientist whose roots trace back to the Land of Enchantment, New Mexico. Raised near the Navajo Nation just outside Gallup, Dr. Andy Annalora has embraced the values of unity, friendship, and cultural diversity and forged a legacy of educational excellence. As we follow Dr. Annalora’s journey, we will uncover the academic milestones, personal passions, and groundbreaking research that define his career.
Dr. Annalora developed a strong foundation in education from an early age. Both parents served as educators for the Bureau of Indian Affairs (BIA), instilling in him the importance of learning and sharing knowledge. After completing high school as the Salutatorian of his graduating class, Dr. Annalora accepted a Regents’ scholarship at the University of New Mexico in Albuquerque, where he pursued a Bachelor of Science in Biochemistry, delving into the intricate world of molecular structures and biochemical processes and setting the stage for his future career in Toxicology.
An artistic representation of the CYP24A1 enzyme which Dr. Annalora crystallized and characterized using x-ray crystallography at The Scripps Research Institute as a postdoctoral trainee. CYP24A1 is overexpressed in many forms of cancer and is an important drug target for several forms of cancer that are responsive to the vitamin D hormone (calcitriol). Here the hydrophobic (yellow cartoon) and hydrophilic (cyan cartoon) structural domains of the monotopic membrane protein are shown surrounding the central substrate access channel and active site that are filled with 4 molecules of the detergent CHAPS (magenta sticks) and a heme molecule (black stick).
Under the guidance of his mentor, Dr. John L. Omdahl, Dr. Annalora became immersed in vitamin D hormone biochemistry and cytochrome P450 gene structural biology. This mentorship laid the groundwork for his future endeavors and propelled him toward a Ph.D. in Biomedical Sciences in the Omdahl Laboratory. His journey continued with a deep dive into the molecular intricacies of the CYP24A1 protein, a vitamin D hormone metabolizing enzyme overexpressed in various forms of cancer. The pursuit of knowledge took Dr. Annalora to the Scripps Research Institute for postdoctoral training, where he accomplished the significant feat of solving the crystal structure of CYP24A1. These academic achievements culminated in an offer of a research faculty position in the Department of Environmental and Molecular Toxicology at Oregon State University in Corvallis, Oregon in collaboration with Dr. Craig Marcus.
The focus of Dr. Annalora’s current research is in the broad field of molecular toxicology with a specific interest in characterizing the gene regulation and protein structure/function of vital drug metabolizing enzymes (CYPs or P450s) and xenosensors (AHR, PXR, CAR, and VDR). This research not only delves into the intricacies of these molecular systems but aims to pave the way for safer and personalized therapeutics for individuals. Current research projects span diverse areas, from RNAseq and bioinformatics analysis of xenobiotic-induced alternative gene splicing to multi-omics analysis of CYP1B1 gene function in ocular wound repair. These projects synergize to address Dr. Annalora’s core toxicological research interest — identifying and characterizing the molecular mechanisms driving adverse health effects of environmental pollution and xenobiotics.
An artistic representation of the ligand-bound PAS-B domain of the arylhydrocarbon receptor (AHR; yellow ball and stick) in complex with its chaperone proteins HSP90 (cyan and green ball and stick) and XAP2 (magenta ball and stick). The AHR is an important xenosensor, highly studied in toxicology, which allows our cells to recognize, bind to and respond to foreign chemicals that enter the body. Dr. Annalora and his collaborators are trying to understand the structural determinants that control ligand recognition, and the activation of the receptor, to understand which environmental pollutants are most likely to drive adverse outcome pathways and disease via excessive AHR signaling.
Dr. Annalora's journey through the scientific landscape is marked by diverse and significant contributions to the field. Early work focused on CYP structure/function for drug discovery, evolving into an exploration of alternative gene splicing in human toxicology. This shift unveiled the role of cell-specific expression of nuclear receptors and CYP gene variants linked to diseases such as cancer, kidney disease, and obesity. He pioneered work in alternative gene splicing of the vitamin D receptor (VDR), opening doors to novel therapeutic opportunities. Splice variants of the VDR, expressed without specific protein domains, showcase alternative functionalities with potential applications in treating disorders like cancer and chronic kidney disease. This line of inquiry even led to the development of a new anti-hypertensive agent, patented in 2020.
The emergence of computational modeling studies in aryl hydrocarbon receptor (AHR) biology reflects another facet of Dr. Annalora's research. Exploring the structural determinants of ligand recognition and studying endogenous ligands produced by the microbiome, his work presents promising avenues for understanding gut health, the gut-brain axis, as well as the progression of tumorigenesis.
Dr. Annalora providing a hands-on demonstration of pipetting technique and the use of PCR in toxicology to undergraduate trainee Zachary Kowash.
Dr. Annalora dedicates much of his efforts to mentoring students and directing research projects centered around xenobiotic metabolizing enzymes and xenosensors. His passion for toxicology emerged as did his use of cutting-edge technology to address critical environmental issues impacting human health. Dr. Annalora remarked that looking at the RNA metabolite patterns of disease progression is much “like detective work”. His goals in the research laboratory are setting the stage for future personalized medicine applications.
In support of student success, Dr. Annalora has taken the lead in converting several of his courses into an Ecampus format, enabling students from across the world to benefit from his knowledge and inspiration. He is currently spearheading efforts to establish an online Graduate Certificate in Toxicology. This unique, interdisciplinary program bridges environmental, molecular, and computational toxicology to explore and predict how chemicals move through the environment and potentially negatively impact living systems in those environments.
Beyond the laboratory and the classroom, Dr. Annalora leads a rich and fulfilling personal life. An avid fisherman, he finds solace in the local rivers, lakes, and ocean. Fly-fishing, with its challenging allure, becomes a source of joy, especially when seeking large steelhead and rainbow trout in the Columbia River Basin and Willamette Valley. Dr. Annalora also enjoys gardening, planting a bountiful vegetable garden every summer. This year, his prized crop (Hatch Green Chile’s from New Mexico, of course) flourished in the Oregon soil offering him a taste of home. Indoors during the rainy season, Dr. Annalora finds comfort in reading Sci-Fi novels, exploring the web, and playing acoustic and electric guitar. A sports enthusiast and the son of a former football coach, Dr. Annalora remains a devoted fan. While now rooting for Beaver Nation at Oregon State University, he maintains a soft spot for his alma mater, the University of New Mexico Lobos.
From the enchanting landscapes of New Mexico to the laboratories of Oregon State University, Dr. Annalora’s pursuit of knowledge in toxicology has not only shaped his career but has the potential to impact the lives of many through safer and personalized therapeutics. As he looks toward the future, his dedication to unraveling the intricacies of molecular biology promises continued discoveries and advancements in human health.