Life sciences

Xinxin Ding, PhD, department head, Pharmacology and Toxicology, College of Pharmacy—studies enzyme function, regulation and genetics as applied to translational research for drug safety and efficacy and genetic and environmental risks for chemical toxicity. Author of nearly 200 peer-reviewed papers, book chapters and articles, he serves as associate editor for “Drug Metabolism and Disposition” and “Acta Pharmaeutica Sinica B.” Grants from the National Cancer Institute and National Institute of Environmental Health Sciences of the National Institute of Health fund his work, in part. Former chair of the NIH XNDA study section (2016-2018), he currently chairs (2018-19) Drug Metabolism and Disposition Division of the American Society for Pharmacology and Experimental Therapeutics..

Plants grow as a result of the proliferation of stem cells and the establishment and maintenance of defined developmental fates in progeny cells. Our major goal is to elucidate general molecular mechanisms used by plants to specify and maintain cell fates, ranging from stem cells to fully differentiated cell types. Both experimental manipulations and the identification of genes responsible for the maintenance of stem cells and for the establishment and maintenance of differentiated cell fates through forward genetic screens implicate intercellular signaling in these processes. Because of the important role of intercellular signaling in the differentiation of cells initiating from meristems, studying receptors is one way to dissect these molecular mechanisms. To understand signaling events that take place in development, we analyze the phenotypes of plants mutant for individual or multiple receptors. My lab has identified key roles for specific receptors during radial patterning in early embryogenesis (Nodine et al., 2007), during the formation of lateral roots (Wierzba and Tax, in preparation), in the formation of fruit organs from stem cells within the fruit (Durbak and Tax, 2011), in the development of vascular tissues (Bryan et al., 2012), and in the process of cell elongation (Li et al., 2002). Future studies will include further analysis of the signaling networks anchored by these receptors, with a specific focus on the transitions between different downstream transcription factor targets. In addition, we are interested in developing approaches to isolate mutants in these receptors to manipulate the architecture and physiological responses of crop plants.

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.

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

Research in my laboratory over the last 30 years has focused on chronic heart failure (CHF), its pathophysiology and the development of new treatments for CHF. We have developed clinically relevant animal models of heart failure that allow us to explore the translational potential of new treatments. Our work initially examined the role of afterload reduction and neurohormal blockade. More recently we have been working with cell-based therapy for CHF using bioengineered scaffolds to prevent left ventricular (LV) remodeling and restore function in the damaged heart. Our most effective scaffold is a biodegradable vicryl mesh with embedded viable neonatal fibroblasts that secrete angiogenic growth factors. This patch increases myocardial blood flow, improves LV systolic function, and reverses LV remodeling if implanted at the time of an acute myocardial infarction. In CHF, this patch still improves myocardial blood flow but does not improve LV function or reverse LV remodeling. Thus, we have an effective delivery system for cell based therapy for CHF that increases myocardial blood flow and provides structural support for new cell growth. We are now focusing on seeding this patch with human inducible pluripotent stem cells in the cardiac lineage, the seeded cardiomyocytes align, communicate, contract in a spontaneous and rhythmic fashion. When implanted in rats with CHF, they improve LV function. We are exploring this patch seeded with human inducible cardiac pluripotent stem cells to treat patients with CHF. Keywords: induced pluripotent stem cells

Joel Cuello, PhD, focuses his research on applying engineering to put biological systems to work. His collaborative research projects, which have been sponsored by DOE, NASA and USDA, among others, are divided into two major thrusts: Bioprocess Engineering and Controlled-Environment Engineering.With bioprocess engineering, Dr. Cuello’s concentrations are on design and scale up of bioreactors for production of biofuels and biochemicals from algae, plant cells and organs. Also, he explores the optimization of algae and cell-culture productivity through biochemical and environmental strategies. Also, he attends to wastewater treatment using algae, microbial mat and hydroponics.In regard to controlled-environment engineering, Dr. Cuello’s concentrations -- for both Earth and Space applications -- are on design of novel lighting systems, including hybrid solar-electric lighting systems, light-emitting diode arrays, and water-cooled high-intensity discharge lamps. He complements this work with trying to design bioproduction systems, including a hybrid hydroponics-and-aquaculture system.

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

Dr. Brinton is the inaugural Director of the UA Center for Innovation in Brain Science at the University of Arizona Health Sciences and Professor of Pharmacology and Neurology, College of Medicine, University of Arizona. Her research is focused on the mechanisms underlying late onset Alzheimer’s and developing therapeutics to prevent, delay and cure the disease. Her discovery research program focuses on systems biology of: 1) Mechanisms underlying risk of Alzheimer’s during female brain aging; 2) Sex differences in mechanisms underlying Alzheimer’s and 3) Regeneration and repair mechanisms to regenerate the Alzheimer’s brain. Insights from her research indicate that the aging brain is dynamic and adaptive. The dynamic adaptive nature of the aging brain has led to an increasing focus on transition states of the aging brain, their plasticity, limits and vulnerability. In her translational and clinical research portfolio she has advanced her basic science discoveries for allopregnanolone and phytoSERM into FDA IND-enabling translational programs and two early phase clinical trials. She has published more than 200 articles in peer-reviewed journals and has authored 29 book chapters and invited reviews and has delivered more than 250 invited presentations worldwide. She holds multiple patents, has co-founded two biotech companies, mentored 22 graduate students, 10 postdoctoral fellows and 56 STAR students. Her research is supported by an NIA Program Project, a NIA R37 MERIT Award, 4 R01s, UF1, and two training grants (T32 and R25). Dr. Brinton has received numerous awards and recognition for her research and STEM education initiatives and has appeared in over 100 media outlets, including national and international broadcasts. Her awards include: “Scientist of the Year” by Alzheimer’s Drug Discovery Foundation, “Woman of the Year” by the California State Senate, “Science Educator of the Year” by the Society for Neuroscience, Los Angeles Magazine “Woman of the Year”, and U.S. News & World Report’s “Ten Best Minds”. For her outstanding work in promoting STEM careers among students of color, President Barak Obama presented her with one of the nation’s highest civilian honors, the Presidential Citizens Medal. The Center for Innovation in Brain Science (CIBS) is focused on mechanistically driven therapeutic development and translational research for age-associated neurodegenerative diseases https://cibs.uahs.arizona.edu/. CIBS was created to address the challenge that in the 21st century there is not a single cure for a single neurodegenerative disorder. Operating as a University based biotech unit, CIBS is unique nationally and perhaps globally, in providing an integrated translational research environment that brings together researchers and clinicians across the spectrum of age-associated neurodegenerative diseases (Alzheimer’s, Parkinson’s, Multiple Sclerosis and Amyotrophic Lateral Sclerosis) and pairs them with world-class experts in computational systems biology, synthetic chemistry, translational drug development, biomarker design, clinical trial operations and regulatory affairs. Since its launch in 2016, CIBS has made remarkable progress; including an impressive portfolio of therapeutics, research awards, transformative educational programs, and growing Arizona’s biotech sector. Select Professional Service 2019 - Present Member, NIH Advisory Committee to the Director 2019 - Present Scientific Advisory Board of National Institute on Aging 2018 National Institute on Aging M2OVE AD Advisory Panel 2018 Co-Chair and Reviewer: Translational Research Program, National Institute on Aging: Division of Neuroscience 2016 - 2019 Member of the Public Education and Communication Committee (PECC) 2015-Present Board of Governors, Alzheimer’s Drug Discovery Foundation, New York, NY 2014-Present Chair, Medical & Scientific Advisory Council Alzheimer’s Association, Los Angeles, CA 2013 – 2017 Member, NIH Center for Scientific Review Advisory Council 2013 – 2016 Member Society for Neuroscience, Committee on Committees 2010 National Institute on Aging Alzheimer’s Advisory Board 2009 – 2013 Member, Alzforum Scientific Advisory Board 2009 – 2013 Member, NIMH IRP Board of Scientific Councilors, NIH 2008 – 2011 Member, Society for Neuroscience Board of Councilors 2008 NIH Blueprint Initiative on K‑12 Activities 2007 – 2008 NIH Blue Ribbon Panel on National Institute of Mental Health Intramural Research Programs 2005 – 2009 External Advisory Board NIH/NIA Women’s Health Initiative Memory Study 1999 – Present Member, Scientific Review Board of Alzheimer’s Drug Development Foundation, NY Select Honors 2017 National Academy of Inventors 2017 Alzheimer’s Drug Discovery Foundation, Melvin Goodes Prize for Excellence in Alzheimer’s Drug Discovery 2017 Disruptive Women to Watch in 2017, Disruptive Women in Health Care 2015 Scientist of the Year Award, Alzheimer’s Drug Discovery Foundation 2014 Los Angeles Woman of the Year, LA Magazine 2010 Presidential Citizens Medal, President Barack Obama 2009 North American Menopause Society /Wyeth Pharmaceuticals SERM Research Award 2006 Science Educator of the Year, Society for Neuroscience 2005 Woman of the Year, California State Senate 2005 10 Best Minds, US News & World Report 2003 University of Southern California Remarkable Woman Award 1999 Laboratory Named “The Norris Foundation Laboratory for Neuroscience Research” Select publications Bacon, E.R., Mishra, A., Wang, Y., Desai, M.K., Yin, F. and Brinton, R.D., 2019. Neuroendocrine aging precedes perimenopause and is regulated by DNA methylation. Neurobiology of aging, 74, pp.213-224. Geifman, N., Kennedy, R.E., Schneider, L.S., Buchan, I. and Brinton, R.D., 2018. Data-driven identification of endophenotypes of Alzheimer’s disease progression: implications for clinical trials and therapeutic interventions. Alzheimer's research & therapy, 10(1), p.4. Mosconi, L., Berti, V., Quinn, C., McHugh, P., Petrongolo, G., Varsavsky, I., Osorio, R.S., Pupi, A., Vallabhajosula, S., Isaacson, R.S., de Leon, M.J., and Brinton, RD., 2017. Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging. Neurology, 89(13), pp.1382-1390. Rettberg, J.R., Dang, H., Hodis, H.N., Henderson, V.W., John, J.A.S., Mack, W.J. and Brinton, R.D., 2016. Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: potential for detecting an at-Alzheimer's risk metabolic phenotype. Neurobiology of aging, 40, pp.155-163. Klosinski, L.P., Yao, J., Yin, F., Fonteh, A.N., Harrington, M.G., Christensen, T.A., Trushina, E. and Brinton, R.D., 2015. White matter lipids as a ketogenic fuel supply in aging female brain: implications for Alzheimer's disease. EBioMedicine, 2(12), pp.1888-1904. Brinton, R.D., Yao, J., Yin, F., Mack, W.J. and Cadenas, E., 2015. Perimenopause as a neurological transition state. Nature reviews endocrinology, 11(7), p.393. Brinton, R.D., 2013. Neurosteroids as regenerative agents in the brain: therapeutic implications. Nature reviews endocrinology, 9(4), p.241.

Research in the Bhattacharya lab focuses on molecular approaches to direct B cell differentiation to establish immunity to infectious disease, and stem cell differentiation for regenerative medicine. Current projects in the lab include: 1) Understanding the cellular basis of antibody-mediated immunity to variable viruses. After infection or vaccination, B cells that recognize the pathogen proliferate and undergo a massive level of expansion. Upon clearance of the infection a small fraction of the "best" B cells are retained to become memory B cells or long-lived plasma cells. Our recent work has established that memory B cells are excellent at recognizing not only the original pathogen, but also mutant escape variants of the pathogen. In contrast, long-lived plasma cells are highly specific only for the original pathogen. We are studying the transcription factors that regulate the memory B cell vs. long-lived plasma cell fate, and are studying mechanisms to alter this fate to provide effective immunity against mutable viruses such as influenza and Dengue. 2) Identifying molecular regulators of the duration of immunity. Most clinically used vaccines rely on the production of antibodies to confer immunity. The duration of immunity can vary greatly between different vaccines, yet the molecular basis of this remains unknown. Current efforts are focused on the identification of genes that regulate plasma cell lifespan and on the features of the vaccine that confer durable antibody immunity. 3) Engineering human pluripotent stem cells to generate antibody-mediated immunity. A small fraction of patients infected with HIV or dengue virus, or vaccinated against influenza develop remarkable antibodies that neutralize nearly all clinical isolates of these viruses. Yet it is unclear how to induce these types of antibodies in the broader population through standard vaccination. Using novel targeted nuclease technologies, we are engineering human embryonic stem cells to express these antibodies and differentiating them into transplantable long-lived plasma cells. The long-term goal of this project is to provide permanent immunity to recipients of these engineered plasma cells.