Natural sciences

Dominic Mcgrath, PhD, set forth a program which involves the use of organic synthesis for the design, development, and application of new concepts in macromolecular, supramolecular, and materials chemistry. Research efforts span a number of areas in the chemical sciences and include studies of: 1) chiral dendritic macromolecules and the effect of chiral subunits on dendrimer conformation, 2) photochromic dendrimers and linear polymers which undergo structural changes in response to visible light, 3) liquid crystalline materials based on dendritic and photochromic mesogens, and 4) synthesis of new ligands based on saturated nitrogen heterocycles.A continuing interest remains in the effect of structural perturbations on the properties and functional of dendritic macromolecules. Part of this research addresses the design, synthesis, and study of dendrimeric materials containing chiral moieties in the interior for influencing the conformational order of these 3-dimensional macromolecules. An ultimate goal is to develop materials active for the selective clathration of small guest molecules. Potential applications include chemical separations, sensor technology, environmental remediation, and asymmetric catalysis.Dr. Mcgrath and his lab team recently developed several new classes of dendritic materials containing photochromic subunits. As nature uses light energy to alter function in photoresponsive systems such as photosynthesis, vision, phototropism, and phototaxis, they use light energy to drive gross topological or constitutional changes in fundamentally new dendritic architectures with precisely placed photoresponsive subunits. In short, they can drive dendrimer properties with light stimuli. Two entirely new classes of photoresponsive dendritic macromolecules have been developed and include: 1) photochromic dendrimers and 2) photolabile dendrimers. Dr. Mcgrath anticipates that switchable and degradable dendrimers of this type will have application in small molecule transport systems based on their ability to reversibly encapsulate guest molecules. He continues to develop these materials as potential transport hosts and photoresponsive supramolecular assemblies.

Membrane proteins play a number of critical biochemical roles and make up the majority of drug targets. Despite their importance, membrane proteins remain challenging systems for analysis due to their amphipathic nature and low expression levels. Moreover, the lipid bilayer can play an important but largely unexplored role in regulating membrane protein structure and function. New analytical and biochemical methods are necessary to better understand and design drugs to target membrane proteins.

My research interests are in the field of theoretical image science with emphasis on medical imaging. I currently study task-based measures of image quality in which one must define the task the images are to be used for and the observer who will be performing this task, to properly measure and optimize the quality of images and imaging systems. We take the stance that imaging systems should be designed to best enable the observer to detect tumors and not base design decisions on resolution, contrast, etc. Topics in my research group include accurate system modeling, statistical modeling, observer performance metrics, signal-detection theory and general image science.

Minkyu Kim, Ph.D., is an Assistant Professor in the Department of Materials Science and Engineering and the Department of Biomedical Engineering at the University of Arizona. He received a M.S. (2006) in Biomedical Engineering and a Ph.D. (2011) in Mechanical engineering and Materials Science at Duke University. During his Ph.D., he worked in the Single-Molecule Force Spectroscopy group led by Prof. Marszalek. He was a postdoc at MIT from 2012 to 2016, and worked in the Bioinspired and Biofunctional Polymers group led by Prof. Olsen. Dr. Kim’s research is focused on the design and development of biopolymer-based functional materials for targeted applications in healthcare and for national defense. Based on his diverse research experiences in the areas of biopolymer nanomechanics, polymer physics and self-assembly, biomolecular engineering and soft materials, his group is currently developing (a) mechanically responsive soft materials that mimic reversible deformability of red blood cell and that can be utilized as targeted drug delivery vehicles for the early treatment of atherosclerosis and (b) nuclear membrane inspired biopolymer materials that selectively filter and neutralize a broad range of bacteria, fungi and viruses for pharmaceutical, food safety, water decontamination and defense applications. In addition to biomaterial development to mitigate atherosclerosis and infectious diseases, Dr. Kim is also interested in addressing how bioinspired design and biosynthesis can be used for the preparation of novel functional materials, how the nanomechanics of folded biopolymers and artificially engineered hyperbranched biopolymer structures can be translated into the mechanics of macromolecular materials that provide new insight into polymer science, and how protein sequences can control parameters that regulate the functional properties of polymeric materials. Lab Website: http://kim.lab.arizona.edu

My research is focused on developing novel optical microscopy technologies and improving patient care using these technologies. My research area includes (1) low-cost smartphone in vivo microscopy, (2) high-speed comprehensive in vivo endomicroscopy, and (3) ultraminiature endomicroscopy. (1) Low-cost smartphone in vivo microscopy: I am currently leading a NIH-sponsored research project for developing smartphone confocal microscope and diagnosing Kaposi's sarcoma in Uganda with the smartphone confocal microscope. I will further advance the smartphone microscopy technology and address other applications, including diagnosis of cervical and oral cancers in low-resource settings, large-population screening of skin cancers in the US, and aiding science and medical educations. (2) High-speed comprehensive in vivo endomicroscopy: I have previously developed a high-speed confocal microscopy system and endoscopic imaging catheters and acquired largest in vivo confocal images of human organ reported. At the UA, I plan to further advance the technology by i) increasing the imaging speed by orders of magnitude and ii) incorporating fluorescence imaging modality. (3) Ultraminiature endomicroscopy: In my previous research, I have developed miniature endoscopic catheters that can visualize internal organs in vivo through a needle-sized device. At the UA, I will develop microscopic imaging catheter with a extremely small diameter and utilize it for guiding cancer diagnosis and treatment.

Christopher Hulme, PhD, focuses on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. Target families of particular current interest for the group are kinases, protein-protein interactions and emerging DNA receptors for indications in oncology. Such efforts are highly collaborative in nature and students will be exposed to the full array of design hurdles involved in progressing molecules along the value chain to clinical evaluation. These efforts will be aided by the group’s interest in both microwave assisted organic synthesis (MAOS) and flow chemistry. Both technologies enable ‘High-throughput Medicinal Chemistry’ (HTMC) and will be supported by similar High-throughput Purification capabilities.The group also has a long standing interest in the development of new reactions that produce biologically relevant molecules in an efficient manner. Front loading screening collections with molecules possessing high ‘iterative efficiency potential’ is critical for expediting the drug discovery process. The discovery of such tools that perturb cellular systems is of high value to the scientific community and may be facilitated by rapid forays into MCR space that can produce a multitude of novel scaffolds with appropriate decoration for evaluation with a variety of different screening paradigms.Novel hypervalent iodine mediated C-H activation methodologies is also an active area of interest. Probing the scope of the transformation below and investigating applications toward the synthesis of new peptidomimetics will be an additional pursuit in the Hulme group.

Despite many therapeutic successes, cancer remains a major cause of mortality in the US. Natural products (NPs) represent the best source and inspiration for the discovery of drugs and molecular targets. Our aim is to discover effective and non-toxic NP-based anticancer drugs. Working with NCI we have recently discovered a class of plant-derived NPs useful in cancer immunotherapy. The main focus of our current research is to utilize medicinal chemistry approach to obtain their analogues for preclinical evaluation. Leslie Gunatilaka is Professor at the School of Natural Resources and the Environment and Director of the Natural Products Center. He is also Adjunct Professor of Department of Nutritional Sciences, and a member of the Arizona Cancer Center. He is a member of several professional societies, editorial boards, and pharmaceutical company advisory groups. He is a Fellow of the Academy of Sciences for the Developing World (TWAS), Italy, and the National Academy of Sciences, Sri Lanka. Dr. Gunatilaka has over 200 peer-reviewed publications and book chapters and over 150 communications in natural product science to his credit. He is the recipient of the Sri Lankan Presidents’ gold medal for “creating a center of excellence in natural products research at the University of Peradeniya, Sri Lanka” (1987), CaPCURE award for “dedication to ending prostate cancer as a risk for all men and their families” (2000), Research Faculty of the Year Award of the UA College of Agriculture and Life Sciences (2003), the UA Asian American Faculty, Staff and Alumni Association Outstanding Faculty Award (2005), and the UA Leading Edge Researcher Award for Innovative Research (2012). He has delivered over 100 invited lectures worldwide and was the Chief Guest and Plenary Lecturer at the International Herbal Medicine Conference held in Sri Lanka (2005), and the Keynote Speaker and the Guest of Honor at Chemtech-2007, an International Conference organized by the Institute of Chemistry, Ceylon. His current research interests include discovery, identification of protein targets, and structure-activity relationship (SAR) studies of natural product-based drugs to treat cancer, neurodegenerative, and other diseases from plants, and plant- and lichen-associated microorganisms, maximization of chemistry diversity and production of microbial and plant secondary metabolites, and scientific investigation of medicinal plants and herbal supplements. Keywords: Natural Product-Based Drug Discovery, Medicinal Chemistry, Cancer Immunotherapeutic Agents

Hendrikus Granzier, PhD, studies the mechanisms whereby the giant filamentous protein titin (the largest protein known) influence muscle structure and function. His lab has shown that titin functions as a molecular spring that mediates acute responses to changing pathophysiological states of the heart. They also study the role of titin in cardiac disease, using mouse models with specific modifications in the titin gene, including deciphering the mechanisms that are responsible for gender differences in diastolic dysfunction. An additional focus of Dr. Granzier’s lab is on nebulin, a major muscle protein that causes a severe skeletal muscle disease in humans. Based on previous work, they hypothesize that nebulin is a determinant of calcium sensitivity of contractile force. To test this and other concepts, he uses a nebulin knockout approach in the mouse. Research is multi-faceted and uses cutting-edge techniques at levels ranging across the single molecule, single cell, muscle, and the intact heart. His research group is diverse and has brought together individuals from several continents with expertise ranging from physics and chemistry to cell biology and physiology.

Michael F. Brown is Professor of Chemistry & Biochemistry at the University of Arizona. He is co-director of the Biological Physics Program and the Chemical Physics Program, and was a co-founder of the Biological Chemistry Program at the University of Arizona. He is internationally renowned for his work on the molecular basis of activation of G-protein-coupled receptors that are the targets for the majority of pharmaceuticals and medicines used by humans. The focus of his work is on biomembranes, with a particular emphasis on lipid-protein interactions in relation to potential drug targets involving membrane proteins. He is involved with investigation of the molecular basis of visual signaling involving rhodopsin. Moreover, Professor Brown is an expert in nuclear magnetic resonance (NMR) spectroscopy. His activities in the area of biomolecular NMR spectroscopy involve the devolvement and application of methods for studying the structure and dynamics of biomolecules. Michael Brown has authored over 130 original research papers, 10 book chapters, 4 book reviews, and has published more than 275 abstracts. His current H-index is 43. He numbers among his coworkers various prominent scientists worldwide. He presents his work frequently at national and international conferences, and is the recipient of a number of major awards. Professor Brown's many contributions have established him as a major voice in the area of biomembrane research and biomolecular spectroscopy. He is frequently a member of various review panels and exerts an influence on science policy at the national level. Among his accolades, he is an elected Fellow of the American Association for the Advancement of Science; American Physical Society; Japan Society for the Promotion of Science; and the Biophysical Society. He is a Fellow of the Galileo Circle of the University of Arizona. Most recently, he received the Avanti Award of the Biophysical Society. This premier honor recognizes his vast and innovative contributions to the field of membrane biophysics, and groundbreaking work in the development of NMR techniques to characterize lipid structure and dynamics. Most recently he presented the 2014 Avanti lecture of the Biophysical Society.