Chemistry & Biochemistry

Haining Zhu

Professor, Pharmacology and Toxicology
Professor, Chemistry and Biochemistry-Sci
Professor, Neuroscience - GIDP
Endowed Chair, R Ken and Donna Coit - Aging and Neurodegenerative Diseases
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-2823

Work Summary

Dr. Zhu is an expert on molecular mechanisms underlying neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). His recent focus is on RNA binding proteins and RNA metabolism in these diseases. With thorough understanding of pathways regulating protein-protein and protein-RNA interactions, protein degradation and aggregation, RNA metabolism and stress granules, he is also interested in developing novel therapeutics.

Research Interest

The Zhu laboratory studies RNA binding proteins and RNA metabolism including protein translation and stress granules under physiological and pathological conditions. We are also interested in protein phase separation and aggregation in vitro and in vivo and their relevance in human diseases. We strive to better understand the molecular mechanisms for neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and other diseases such as cancer. In addition, we are interested in therapeutic development targeting the molecules identified in the mechanistic studies.

Nitesh Kumar Khandelwal

Postdoctoral Research Associate I
Research Associate
Primary Department
Department Affiliations
Contact
(520) 621-4646

Research Interest

Throughout my career I have been interested in the transporter biology. During my Ph.D., I have worked on functional characterization of ABC transporters in human pathogenic yeast C. albicans. Presently, in Tomasiak lab, I am applying the cryo-EM technique for determination of molecular structure of eukaryotic ABC transporter during different steps of substrate transport and structural basis of post-translational modification in regulation of transporters function. My long-term goal is to channel my passion for science to contribute towards the better health of humans. I wanted to work as an independent researcher in a research institute/university.

Thomas M Tomasiak

Assistant Professor, Chemistry and Biochemistry
Assistant Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 621-4646

Research Interest

Our group focuses on the regulation of nutrient and drug transport in disease with an emphasis on fungal pathogenesis and cancer. In every eukaryotic cell, cell stress and nutrient acquisition must be closely tied to the cell cycle to ensure a sufficient environment for mitosis. This coordination is of vital importance to rapidly dividing cells in stressful environments, such as pathogens or metastatic cancer cells, and is carried out by a complex network of transporters and transporter regulatory proteins. They form the basis of drug resistance and virulence in many diseases. We use a multidisciplinary approach to understanding these transport processes which includes cryo electron microscopy, biochemistry, and cell biology. Our ultimate goal is to understand these transporter networks and their regulation in sufficient detail to generate molecules that target them as antifungal or anticancer therapeutics.

Steven D Schwartz

Professor, Chemistry and Biochemistry-Sci
Professor, Applied Mathematics - GIDP
Regents Professor
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 621-6363

Research Interest

My research interests relate to the theoretical chemistry and biophysics of complex systems. Current areas of funded research include the study of protein dynamics in enzymatic reactions, quantum tunneling in enzymatic reactions, modeling of the cardiac thin filament with application to disease mechanism, and the study of the properties of micelles created from green surfactants. I am chair elect of the biological physics division of the American Physical Society, a Fellow of the APS and the AAAS.

Jacob C Schwartz

Associate Research Professor, Pharmacology
Assistant Professor, Chemistry and Biochemistry - Med
Assistant Professor, Chemistry and Biochemistry-Sci
Assistant Professor, Neuroscience - GIDP
Associate Professor, Cancer Biology - GIDP
Associate Professor, Neuroscience - GIDP
Assistant Professor, BIO5 Institute
Primary Department
Contact
(520) 621-0877

Research Interest

Every investigation that they have pursued, even investigating novel disease models, has produced profound discoveries in basic biology and biochemistry. They are currently working in collaborations with labs to exploit three system to explore the basic function of the RNA-binding protein FUS. First, they are collaborating with the lab of Rob Batey (UC Boulder) to investigate the role of RGG-rich domains in mediating RNA recognition. Next they are collaborating with lab of Kate Fitzgerald (U Mass Med) to investigate the role of FUS in transcriptional pause release and initiation as macrophage cells respond to stimulation of Toll-like receptor 4. Lastly, they are collaborating with the lab of Ran Taube (Ben-Gurion U) to investigate the role of FUS as a scaffold protein to promote the formation of the Super Elongation Complex (SEC) both genome-wide and for the Tat gene in HIV. They are also pursuing the role of FUS and noncoding RNAs in DNA damage repair. They believe that the function of FUS in affecting transcription is also crucial to the repair of DNA damage in cells.

Jeffrey Pyun

Professor, Chemistry and Biochemistry-Sci
Professor, Optical Sciences
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-1834

Research Interest

Our research program is focused on the synthesis and characterization of novel polymeric and composite materials, with an emphasis on the control of nanoscale structure. Recent developments in polymer and colloid chemistry offer the synthetic chemist a wide range of tools to prepare well-defined, highly functional building blocks. We seek to synthesize complex materials from a "bottom up" approach via the organization of molecules, polymers and nanoparticles into ordered assemblies. Control of structure on the molecular, nano- and macroscopic regimes offers the possibility of designing specific properties into materials that are otherwise inaccessible. We are particularly interested in compatabilizing interfaces between organic and inorganic matter as a route to combine the advantageous properties of both components. This research is highly interdisciplinary bridging the areas of physics, engineering and materials science with creative synthetic chemistry.

Robin Polt

Professor, Chemistry and Biochemistry-Sci
Professor, Neuroscience - GIDP
Professor, Pharmacology and Toxicology
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 370-2654

Research Interest

Dr. Polt began his research career by developing methods for amino acid synthesis in Prof. Marty O’Donnell’s lab at IUPUI. After that he was trained in the art of Organic Synthesis in the laboratories of Profs. Gilbert J. Stork at Columbia University and Dieter Seebach at the ETH in Zürich. He has continued to develop novel synthetic methods for amino acids, amino alcohols, glycosides and glycopeptides. Application of these methods resulted in the production of a number of pharmacologically active glycopeptides (GPCR agonists), alkaloid-like inhibitors of glycolipid processing enzymes and glycosyltransferases, as well as glycolipids with biological activity such as glycosphingolipids and rhamnolipids. The biological focus of his work has been in attempting to understand the chemistry of carbohydrates (e.g. glycolipids, glycoproteins) at cell membranes, membrane trafficking, and using these insights to design glycopeptide drugs from endogenous peptide neurotransmitters (neuromodulators, hormones) with enhanced stability in vivo that are capable of penetrating the Blood-Brain Barrier and interacting with GPCRs as agonists or antagonists. Presently, Polt studies the design, synthesis and testing of agonists related to the hormones Oxytocin and PACAP (Pituitary Adenyl Cyclase Activating Peptide), as well as other glycopeptide drug candidates.

Clinical applications of the glycopeptide drugs include pain, opioid use disorder, migraine, Parkinsons, Alzheimers and other neurogenerative diseases. In addition to lecturing and laboratory teaching during 35 years at the University of Arizona, and the publication of more than 137 scientific papers, he has mentored a large number of undergraduate, graduate (21 Ph.D.s granted, 2 in progress) and post-doctoral students who have taken positions in academia, industry and the US government. His Ph.D.s have hailed from the US (10), Czech Republic*, China, Germany*, India, Iran*, Ireland, Jordan*, Kenya*, Korea, Mexico* and Sri Lanka. Six of these Ph.D. graduates (*) have gone on to become naturalized citizens or obtain permanent resident status. Recent undergraduates associated with his research group have gone to graduate schools at Harvard, MIT, Boston University, University of Wisconsin, and Columbia University.

Jeanne E Pemberton

Professor, Chemistry and Biochemistry-Sci
Regents Professor
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 621-8245

Research Interest

Jeanne Pemberton, PhD, is a household name in chemistry departments across the country. Her research on surface vibrational spectroscopy has enabled fundamental advances in the field of analytical chemistry.In her 25 years at The University of Arizona, Pemberton has received more than 40 research grants. Among the many boards and committees she serves, she was the chair of the Math and Physical Sciences Advisory Committee at the National Science Foundation in 2004. In addition to receiving the College of Science Distinguished Teaching Award, she has also received the distinguished American Chemical Society Award for Excellence in Analytical Chemistry, which is among the highest honors in her field.Dr. Pemberton’s group research seeks to develop an understanding of chemistry in several technologically important areas including electrochemistry and electrochemically-related devices, chromatography, self-assembled monolayers, surfactant systems, and environmental and atmospheric systems. Methodologies employed for these efforts include surface vibrational spectroscopies, near-field optical methods, electrochemistry, x-ray photoelectron spectroscopy, Auger electron spectroscopy, LEED, work function measurements, ellipsometry, electron microscopy, and the scanning probe microscopies AFM and STM. Molecular nanoscale imaging exists prominently in the ability to elucidate structural and mechanistic details of surface and interfacial chemistry.Two images of transient intermediate states on NaCl in its reaction with the mineral acids, HNO3 and H2SO4, are shown below. These transient structures are formed en route to the final surface products of crystalline NaNO3 and NaHSO4, respectively.Specific interfacial systems of interest include electrochemical battery and electroluminescent and electrochromic devices, models of these devices fabricated and studied in ultrahigh vacuum, organized molecular assemblies at solid surfaces or air-water interfaces formed spontaneously or by self-assembly or Langmuir-Blodgett techniques, chromatography stationary phase systems, soil and mineral systems important in the fate and transport of environmentally important chemicals, and surfaces such as ice, mineral acids, and alkali halides important in atmospheric processes.

Jon T Njardarson

Professor, Chemistry and Biochemistry-Sci
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-0754

Research Interest

Research in Jon’s Group is focused on two main areas of investigation. One part of the group is dedicated to the development of useful new synthetic reactions, while the other half is committed to designing and executing creative efficient routes towards natural products with promising biological profiles. Exciting outgrowths of these two programs are the unique structural product collections they afford. In our world, these valuable collections then find a new home in the assays of our biological collaborators and begin their new journey filled with exciting unknown observations and discoveries. Currently, we are working on advancing three main methodological programs: These programs are dedicated to designing and studying: 1) new catalytic ring expansion of strained heterocyclic structures, 2) valuable reaction cascades and 3) new reagents for oxidative dearomatizations. Students working on these important programs are expected to demonstrate to the community the full scope and limitations of their new discovery, and investigate mechanism and develop asymmetric variants of the reaction when appropriate. I view a well-matched application of their new reaction towards a natural product, pharmaceutical agent or other valuable target structures to be an important part of their training. Our natural product portofolio is primarily dedicated to the synthesis of complex bridged bicyclic structures. Each target structure is carefully selected for its unique architecture and reported biological activity. Students are expected to devise synthetic blueprints that are both creative and concise. Each synthetic path should be based on a novel disconnection approach that should also employ a new or underutilized reactions or reaction sequences. It is expected that many of these approaches will serve as examples or inspirations for others to follow in their molecular designs. Targets of interest in this category include vinigrol, hypoestoxide, hyperforin, verticillol and guttiferone G. Following completion these targets otherwise inaccessible natural product hybrid collections will be assembled and tested in appropriate assays in addition to being screened further for alternate functional value or insights.

William R Montfort

Professor, Chemistry and Biochemistry-Sci
Professor, Molecular and Cellular Biology
Professor, Applied Mathematics - GIDP
Professor, Cancer Biology - GIDP
Professor, Genetics - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 621-1884

Work Summary

We investigate how proteins work in healthy organisms and how they fail in disease. We determine the atomic structures of proteins and the underlying biochemistry that gives rise to protein function. We also develop new proteins as drug targets for treating cancer and cardiovascular disease.

Research Interest

William Montfort, PhD, determines the atomic structures of proteins and seeks to understand how protein structure gives rise to protein function – both in vitro and in living cells. At their heart, the problems have a fundamental structure-function question, but also address questions of importance to human health. Approaches include X-ray crystallography, rapid kinetic measurements, spectroscopy, theory, protein expression, drug discovery, molecular genetics and related techniques.Dr. Montfort is particularly interested in nitric oxide signaling mechanisms. Nitric oxide (NO) is a small reactive molecule produced by all higher organisms for the regulation of an immensely varied physiology, including blood pressure regulation, memory formation, tissue development and programmed cell death. He is interested in two NO signaling mechanisms: binding of NO to heme and the nitrosylation (nitrosation) of cysteines. NO, produced by NO synthase, binds to soluble guanylate cyclase (sGC) at a ferrous heme center, either in the same cell or in nearby cells. Binding leads to conformational changes in heme and protein, and to induction of the protein’s catalytic function and the production cGMP. NO can also react with cysteine residues in proteins, giving rise to S-nitroso (SNO) groups that can alter protein function. He continues to study the mechanistic details surrounding cGMP and SNO production, and the signaling consequences of their formation.For reversible Fe-NO chemistry, Dr. Montfort is studying soluble guanylate cyclase and the nitrophorins, a family of NO transport proteins from blood-sucking insects. Our crystal structures of nitrophorin 4 extend to resolutions beyond 0.9 angstroms, allowing us to view hydrogens, multiple residue conformations and subtle changes in heme deformation. For reversible SNO chemistry, he is studying thioredoxin, glutathione S-nitroso reductase (GSNOR) and also sGC. For regulation in the cell, Dr. Montfort and his group have constructed a model cell system based on a human fibrosarcoma called HT-1080, where sGC, NO synthase, thioredoxin and GSNOR can be manipulated in a functional cellular environment. With these tools, they are exploring the molecular details of NO signaling and whole-cell physiology, and undertaking a program of drug discovery for NO-dependent diseases. Keywords: Structural Biology, Drug Discovery, Cancer, Cardiovascular Disease