Medical research

Dr. Gerald (‘Gerry’) Maggiora, PhD, received a Bachelor of Science in chemistry and a PhD in biophysics from the University of California, Davis. He has more than 20 years experience in academia as a professor of chemistry and biochemistry at the University of Kansas, as well as five years as a professor in the College of Pharmacy at the University of Arizona. He has a comparable amount of experience in the pharmaceutical industry, where he served as the Director of Computer-Aided Drug Discovery for three different companies. His early work spanned numerous fields related to the development of quantum mechanical and molecular mechanics methods and their application to problems of mechanistic organic chemistry, vision, photosynthetic energy conversion, and the structural chemistry of drugs, biomolecules, and proteins. After joining the pharma industry, he directed his efforts towards the development and application of similarity and diversity methods and the analysis of biologically relevant chemical space to drug research. His recent work expands the concept of chemical space to include activity landscapes, which extend chemical spaces by including data on the activity of compounds in these spaces. This led to the notion of activity cliffs, which arise when two similar compounds exhibit significantly different activities, a phenomenon that runs counter to the well-known ‘Similarity-Property Principle’ that similar compounds tend to exhibit similar properties. Although relatively rare, activity cliffs provide significant information on structure-activity relationships that lie at the heart of drug design. He has also developed network-based representations of chemical space that circumvent many of the issues associated with the representation of these very high-dimensional spaces. He is currently continuing his work in this area. In recognition of his work in chemical informatics he received 2008 Herman Skolnik Award in Chemical Informatics presented by the Division of Chemical Information of the American Chemical Society.

Esther Sternberg, MD, is internationally recognized for her discoveries of the science of the mind-body interaction in illness and healing. She is also a major force in mind-body-stress-wellness and environment inter-relationships. Dr. Sternberg is recognized by the National Library of Medicine as one of 300 women physicians who changed the face of medicine, and by the National Institutes of Health as Anita B. Roberts "Distinguished Women Scientists at NIH" lecturer. In 2011 Trinity College, Dublin awarded her a Doctorate Honoris Causa (Honorary Doctorate) in Medicine for her contributions to medicine, on the occasion of the 300th Anniversary of the founding of Trinity College School of Medicine. Currently Research Director for the Arizona Center for Integrative Medicine at the University of Arizona, Dr. Sternberg was previously Section Chief of Neuroendocrine Immunology and Behavior at the National Institute of Mental Health; Director of the Integrative Neural Immune Program, NIMH/NIH; and Co-Chair of the NIH Intramural Program on Research on Women's Health.

Marek Romanowski, PhD, and his work on translating physics into medical products have huge implications for the evolution of personalized medicine. On cue, a tiny pillbox of gold floating in your bloodstream can deliver its medicine exactly to the right cell, one that is sick with cancer, avoiding all of your healthy cells. A gold capsule – about 50 to 200 nanometers in diameter, large enough to do the work of transporting a few molecules of medicine and respond to light signals – is too large to pass out through the kidneys. But on command by an enzyme, it can fall apart into pieces smaller than 10 nanometers, just a few molecules. The new size can easily leave our bodies at no risk. The gold pillbox has many other possible applications. In addition to delivering a drug, it can become a part of a diagnostic test, or deliver genetic material to a cell to permanently modify the cells’ DNA—a key step in gene therapy.

Laurence Hurley, PhD, embraces an overall objective to design and develop novel antitumor agents that will extend the productive lives of patients who have cancer. His research program in medicinal chemistry depends upon a structure-based approach to drug design that is intertwined with a clinical oncology program in cancer therapeutics directed by Professor Daniel Von Hoff at TGen at the Mayo Clinic in Scottsdale. Dr. Hurley directs a research group that consists of a team of graduate and postdoctoral students with expertise in structural and synthetic chemistry working alongside students in biochemistry and molecular biology. NMR and in vivo evaluations of novel agents are carried out in collaboration with other research groups in the Arizona Cancer Center. At present, they have a number of different groups of compounds that target a variety of intracellular receptors. These receptors include: (1) transcriptional regulatory elements, (2) those involved in cell signaling pathways, and (3) protein-DNA complexes, including transcriptional factor-DNA complexes.In close collaboration with Dr. Gary Flynn in Medicinal Chemistry, he has an ongoing program to target a number of important kinases, including aurora kinases A and B, p38, and B-raf. These studies involve structure-based approaches as well as virtual screening. Molecular modeling and synthetic medicinal chemistry are important tools.The protein–DNA complexes involved in transcriptional activation of promoter complexes using secondary DNA structures are also targets for drug design.

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.

David Harris, PhD, occupies research efforts directed at the application of (cord blood and adipose) stem cells to transplantation, regenerative medicine and tissue engineering. The difficulty in locating bone marrow donors for patients needing transplants, particularly for minority patients, led to the investigation of other potential sources of stem cells. One such source that has become a viable alternative to bone marrow is umbilical cord blood. Not only has the use of cord blood allowed more patients to go to transplant due to less restrictive matching requirements between donor and recipient, but cord blood transplants are associated with fewer post-transplant complications, such as a lower incidence and severity of graft-versus-host disease (GVHD). In 1989, he began work on the use of cord blood for transplantation, which led to the establishment of the first cord blood bank in the United States in 1992, which is currently the largest such establishment in existence. Work continues today using animal models for cord blood transplantation to explore such research areas as graft-versus-leukemia, GVHD, regenerative medicine and tissue engineering applications. However, studies performed in his lab examining the use of cord blood stem cells in regenerative medicine is now our major emphasis. Work in regenerative medicine has focused on several specific areas of interest. The first area is the use of stem cells in an ischemia/reperfusion injury model of myocardial infarction in a rat model, with positive results. Efforts are underway to understand the molecular mechanisms involved and to derive small molecule drugs in collaboration with Dr. M. Gaballa at Sun Health Research Institute. Secondly, Dr. Harris has been successful in deriving epithelial tissues in vitro that mimic corneal tissues, both morphologically and histologically. When transplanted in vivo in rabbits, the tissues are equivalent to cadaver corneas in terms of sight restoration and function. Dr. Harris and his team are currently developing a human-to-human eye model that will avoid some of the xenogeneic complications associated with the rabbit model, in conjunction with the Dept. of Ophthalmology.Third, they have successfully derived glial, astrocyte and oligodendrocyte cell types from cord blood stem cells in vitro. Currently, these cells are used to study pediatric HIV infection at the molecular level, but are also amenable to work in Parkinson’s and spinal cord injury models. Dr. Harris is now collaborating with Dr. Madhavan of Neurology to study Parkinson’s disease and with Dr. Rogers of Stanford Research Institute to study Alzheimer’s disease. Fourth, recent work has begun comparing various stem cells sources (cord blood, bone marrow and adipose tissue) for the capacity to be used in regenerative medicine. Finally, over the past year they have investigated the use of cord blood stem cells for epithelial wound healing, with the goal being the treatment of non-healing wounds and ulcers in diabetic and bed-ridden patients. It has been found that injections of bone marrow stem cells, both intravenously as well as in the wound margins, significantly reduce healing time as well as minimizing scar formation. Of interest, the age of the recipient plays a significant role in wound healing. Keywords: stem cells, regenerative medicine, biobanking

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

I am a senior research scientist and oversees medicinal chemistry research at BIO5 Institute's drug discovery initiative. I oversee group of medicinal chemistry involved in the development of small molecule therapeutics for idiopathic pulmonary fibrosis (IPF), neuropathic pain, acute lung injury and cancer. I am co-founder of Reglagene and Regulonix - two biotech companies with startup technology from the University of Arizona. I have 15 years' experience in medicinal chemistry with expertise in translational drug development. I am also a co-inventor of small molecules targeting hTERT and MYC for the treatment of glioblastoma, melanoma, lymphomas and prostate cancer. Our work in the area of neuropathic pain has led to successful funding from Tech Launch Arizona and will result in STTR funding from NIH.

Dr. Minying Cai is currently a research professor in the Department of Chemistry and Biochemistry at the University of Arizona. She has been working in the Chemistry & Biochemistry department for more than 16 years and has more than 100 publications in the area of novel drug discovery for obesity, diabetes, cancer and pain. Dr. Cai received the Ph.D. at the University of Arizona in Biochemistry and Molecular Biophysics in 2004. Before that, she had been working in Shanghai Institute of Materia Medica; Shanghai Research Center of Biotechnology in Chinese Academy of Sciences. Dr. Cai has been working on peptide based drug discovery for more than 23 years, starting with discovery of developing anti-microbial peptide and insulin related peptide drug. Sixteen years ago, she started working on melanotropin and opioid related drug discovery. Dr. Cai's research in peptides involves highly multidisciplinary areas including chemistry and biochemistry; molecular pharmacology, molecular imaging, and cancer research, with expertise in molecular pharmacology, synthetic, organic and peptide methodology, chemical and biophysical analysis and evaluation, and in vitro and in vivo expression. Dr. Cai is currently working on several projects at the interface of chemistry, pharmacology and biology within the areas of: 1. Structure based drug design and synthesis of GPCR ligands, including developing selective hMCRs ligand; 2. Developing novel biophysics tools for molecular imaging; novel biomarker for high-throughput screening system. 3. Exploiting novel scaffold via computational chemistry for small molecule therapeutics for energy balance and cancer study; 4. Creating a nanostructured integrated platform for biodetection and imaging-guided therapy. Keywords: Drug Discovery, Melanoma Prevention, neurodegenerative diseases, Obesity and Diabetes, Melanocortin System

Dean Billheimer, PhD, works with the Arizona Statistics Consulting Laboratory (StatLab) to partner with scientists and physicians to advance discovery and understanding. The 'Stat Lab' provides statistical expertise, personnel and computing resources to facilitate study design and conduct, data acquisition protocols, data analysis, and the preparation of grants and manuscripts. Dr. Billheimer also works to adapt and develop new statistical methods to address emerging problems in science and medicine. Dr. Billheimer facilitates discovery translation and economic development by consulting with public and private organizations external to the University of Arizona. Keywords: Biostatistics, Bioinformatics, Study Design, Bayesian Analysis