Transition metals such as Fe, Cu, and Zn are micronutrients that have critical roles at the host-pathogen interface as both the host and pathogen need them for survival. The host has developed innate immune strategies to sequester metals such as Fe which pathogens need for survival as well as strategies to secrete certain metals such as Cu to exert toxic effects on the pathogen. In return, pathogens have evolved strategies to scavenge metals they need, as well as export or store excess metal. Candida albicans, is an opportunistic fungal pathogen that has the capacity to cause systemic infections that can lead to death in immunocompromised and immunosuppressed populations. Azoles, such as fluconazole, are one of the four classes of antifungals that are FDA approved and are a first line treatment for C. albicans infections.  Our lab has shown significant changes to metallohomeostasis of C. albicans as a result of fluconazole treatment. In this talk, I will discuss our work to determine how C. albicans overcomes azole treatment by modifying Cu homeostasis pathways. I will also discuss a potential strategy that focuses on metal dyshomeostasis and takes advantage of our innate immune system to develop a possible treatment for C. albicans infections.

Abstract: The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this resistance phenotype. Thus, an approved CYP1B1 inhibitor may be of immense benefit to cancer patients struggling against chemotherapy-resistant disease.

However, developing selective inhibitors of CYP1B1 is challenging due to the existence of approximately fifty related cytochromes P450 found in humans which share similar structural features. Confounding this fact, CYP1B1 preferentially binds substrates of low three-dimensional complexity and with high lipophilicity, which from a synthetic viewpoint are relatively nondescript, making rational inhibitor design difficult.

This work offers new synthetic approaches toward the solution to the challenge of developing selective CYP1B1 inhibitors. The first part of the work describes the discovery and mode of action of a previously unknown inhibitor of CYP1B1 active at sub-nanomolar concentrations, and with unprecedented selectivity compared to existing inhibitors. Next, the pharmacokinetic optimization of this lead compound was undertaken resulting in an improved lead with excellent metabolic stability for future applications in disease models, and with the long-term goal of translation into the clinic for use in human patients. Together, the development of a series of new molecular entities is described which enable the exquisite control of the activity of this medically relevant enzyme and is an important step toward the development of drug candidates.

Abstract: In this seminar, we will focus on our recent work on two different thin film systems – metal halide perovskites and organic semiconductors.For one, through proper control of processing, we are able to realize pinhole free organic semiconductor films with single crystal grains with mm dimensions. We have found that transport in these films is considerably improved compared to disordered films, and that organic solar cells incorporating these long-range-ordered films exhibit highly delocalized, and band-like charge transfer (CT) states, contributing to noticeably lower energy losses. We will discuss these aspects and our understanding to-date of which molecules are amenable to the formation of such films, and how to propagate their growth. Also, organic hole transport materials (HTMs) are ubiquitous in halide perovskite solar cells, but what is less well known is that shallow HTMs that facilitate hole extraction from the perovskite also enable halogen transport. We will present our understanding of this phenomenon, as well as impacts to devices with regard to Au diffusion.

Bio: Barry Rand earned a BE in electrical engineering from The Cooper Union in 2001. Then he received MA and PhD degrees in electrical engineering from Princeton University, in 2003 and 2007, respectively. From 2007 to 2013, he was at imec in Leuven, Belgium, ultimately as a principal scientist, researching the understanding, optimization, and manufacturability of thin-film solar cells. Since 2013, he is in the Department of Electrical Engineering and Andlinger Center for Energy and the Environment at Princeton University, currently as a Professor. Prof. Rand’s research interests highlight the border between electrical engineering, materials science, chemistry, and applied physics, covering electronic and optoelectronic thin-films and devices. He has authored over 160 refereed journal publications, has 25 issued US patents, and has received the 3M Nontenured Faculty Award (2014), DuPont Young Professor Award (2015), DARPA Young Faculty Award (2015), and ONR Young Investigator Program Award (2016).

Speakers
	Prof. Barry Halliwell National University of Singapore D. Phil. (Oxford), D. Sc. (London) Chairman, BMRC Advisory Council (BMAC), Agency for Science, Technology & Research (A*STAR) Distinguished Professor, Department of Biochemistry , National University of Singapore (NUS) Senior Advisor, Academic Appointments and Research Excellence, Office of the Senior Deputy President and Provost, NUS Program Leader, Neurobiology Research Program, Life Sciences Institute Professor Halliwell graduated from Oxford University with BA (first class honours) and D.Phil degrees. He holds a Doctor of Science degree from the University of London. He was a faculty member with King’s College London (1974-2000) and held a prestigious Lister Institute Research fellowship. He was a Visiting Research Professor of Internal Medicine and Biochemistry at the University of California Davis (1995-1999). He now holds several key positions in Singapore, as indicated above. Professor Halliwell is recognized for his seminal work on the role of free radicals and antioxidants in biological systems, being one of the world’s most highly-cited researchers with a Hirsch-Index of 168 (Based on Scopus, Jan 2023). His Oxford University Press book with John Gutteridge, Free Radicals in Biology and Medicine, now in its fifth edition (2015), is regarded worldwide as an authoritative text. He was honored as a Citation Laureate (2021) for pioneering research in free-radical chemistry including the role of free radicals and antioxidants in human disease. The distinction is awarded by Clarivate to researchers whose work is deemed to be of “Nobel Class” as they are among the most influential, even transformative, in their fields. He was one of 16 scientists (only three in Chemistry) listed in the 2021 Hall of Citation Laureates. Group Page 1 Group Page 2
	Prof. Marzia Perluigi Sapienza University of Rome Marzia Perluigi, PharmD, Ph.D., Head of Laboratory of Redox Biochemistry in Neuroscience (LRBN). Professional appointments: Professor of Biochemistry, Department of Biochemical Sciences “A. Rossi Fanelli" – Medical School Sapienza University of Rome. Fields of Expertise: Biochemistry and cell biology. The major research interest is the study of the role of oxidative stress in Down Syndrome (DS) and Alzheimer Disease (AD). Projects involve both the analysis of post-mortem brains, biological fluids, and cellular and animal models of the diseases. Current projects focus on defects of energy metabolism, failure of protein quality control (UPS and autophagy), impairment of mitochondrial activity, both in DS and AD. Further, preclinical studies are ongoing to test the neuroprotective effects of selected compounds able to prevent/slow the onset of dementia. Group Page
	Prof. Mark Mattson Johns Hopkins University Mark Mattson is the former Chief of the Laboratory of Neurosciences at the National Institute on Aging and is now on the faculty of Neuroscience at Johns Hopkins University School of Medicine. His research has advanced an understanding of the cellular signaling mechanisms that control the formation and plasticity of neuronal networks in the brain, and cellular and molecular mechanisms of brain aging and neurodegenerative disorders. His research has also elucidated how the brain responds adaptively to challenges such as fasting and exercise, and he has used that information to develop novel interventions to promote optimal brain function throughout life. Dr. Mattson is among the most highly cited neuroscientists in the world with more than 900 publications and 200,000 citations. He was elected a Fellow of the American Association for the Advancement of Science and has received many awards including the Metropolitan Life Foundation Medical Research Award and the Alzheimer’s Association Zenith Award. Mattson is the author of the book "The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance."

On Thursday, April 20th, the day before the Naff Symposium, the Chemistry Department also is hosting a Roundtable seminar involving three Department of Biochemistry faculty members from the Sapienza University of Rome, all of whom do research on Alzheimer disease and Down syndrome (persons with DS nearly always exhibit Alzheimer disease neuropathology in brain and dementia later in life).  Prof. Marzia Perluigi, one of our Naff Symposium presenters, also is from the Department of Biochemistry at the Sapienza University of Rome. This Roundtable seminar will begin at 1:30 pm in CHEM-PHYS Room 114 with a Q&A session from 2:30-3:00 pm.

Click here for more information about the event.

2023 Naff Symposium Committee

Prof. Allan Butterfield - (Chemistry) [Chair]

Prof. Marcelo Guzman - (Chemistry)

Prof. Daret St. Clair - (Toxicology/Cancer Biology)

This lecture series commemorates Professor Dawson's leadership in the Department and features speakers noted for the quality, depth and breadth of their research.

Dr. Jeffrey Moore

Moore Lab

Jeffrey Moore received his B.S. in chemistry (1984) and Ph.D. in materials science and engineering with Samuel Stupp (1989), both from the University of Illinois. He then went to Caltech as a National Science Foundation Postdoctoral Fellow working with Robert Grubbs. In 1990, he joined the faculty at the University of Michigan in Ann Arbor and in 1993 returned to the University of Illinois, where he was Professor of Chemistry, as well as a Professor of Materials Science & Engineering until 2022 and was also selected as the Stanley O. Ikenberry Endowed Chair in 2018. Jeff is a member of the National Academy of Sciences and a fellow of the American Academy of Arts & Sciences, the American Association for the Advancement of Science and the American Chemical Society (ACS); he has received the Campus Award for Excellence in Undergraduate Teaching and has been recognized as a “Faculty Ranked Excellent by their Students.”

For 14 years he served as an associate editor for the Journal of American Chemical Society. In 2014, he was selected as a Howard Hughes Medical Institute Professor and in 2016 was chosen as the recipient for the ACS Edward Leete Award in Organic Chemistry. He received the Royal Society of Chemistry’s Materials Chemistry Division 2018 Stephanie L. Kwolek Award and was part of a team that was honored with the Secretary of Energy Honor Award, Achievement Award the same year. Jeff was also awarded the 2019 National Award in Polymer Chemistry by the American Chemical Society. He has published over 400 articles covering topics from technology in the classroom to self-healing polymers, mechanoresponsive materials and shape-persistent macrocycles. He served as the Director of the Beckman Institute for Advanced Science and Technology at the University of Illinois from 2017-2022. In this role, he received the 2021 Executive Officer Distinguished Leadership Award from the UIUC Campus.

"Polymeric Materials for Lifecycle Control"

In this talk I will discuss the molecular design of organic structural materials that mimic living systems’ abilities to protect, report, heal and even regenerate themselves in response to damage, with the goal of increasing lifetime, safety and sustainability of many manufactured items. I will emphasize recent developments in frontal ring-opening metathesis polymerization (FROMP)to manufacture composites with minimal energy consumption. The talk will conclude by introducing the idea of morphogenic manufacturing in which we aim to achieve symmetry breaking in neat polymerization reactions through a coupled reaction-diffuse process; the longterm vision is self-patterned form and function in synthetic materials.

References:

1. Patrick, J.F.; Robb, M.J.; Sottos, N.R.; Moore, J.S.; White, S.R. Polymers with Autonomous Life-cycle Control, Nature, 2016, 540, 363-370.

2. Robertson, I.D.; Yourdkhani, M.; Centellas, P.J.; Aw, J.; Ivanoff, D.G.; Goli, E.; Lloyd. E.M.; Dean, L.M.; Sottos, N.R.; Geubelle, P.H.; Moore, J.S.; White, S.R. Rapid Energy-efficient

Dr. Jeremy Lohman

Abstract: The biosynthesis of both fatty acids and polyketides involves a common reaction, the iterative carbon-carbon bond formation between acyl-thioesters and malonyl-thioesters. While fatty acids and polyketides are essential to society for a plethorea of reasons, how the underlying carbon-carbon bond forming reactions occur remains an open question. Malonyl-thioesters are akin to biochemical hot-potatoes, because they are prone to hydrolysis and decarboxylation. While these two high-energy reactions are exploited by nature for biosynthetic purpose, they plague the structural biologist. We developed molecules that look like malonyl-thioesters but are much more stable, thus we have chilled the hot-potato. These stable malonyl-thioester analogs have provided us with insight into the catalysis of three enzymes. Our preliminary studies with these malonyl-thioester analogs demonstrate that we will be able to generate insight into fatty acid and polyketide biosynthesis, paving the way for new routes to drugs, agrochemicals and biofuels.

Dr. Francis Yoshimoto 

The Yoshimoto research laboratory at UTSA harnesses the power of synthetic chemistry to solve challenging problems relevant to human health.

Artemisinin, one of the topics of the 2015 Nobel Prizes in Medicine, is an endoperoxide-containing sesquiterpenoid plant natural product used to treat malaria. The biosynthesis of the endoperoxide functional group, which gives the natural product its antimalarial activities, has been controversial. Using isotope-labeling strategies, we have elucidated the mechanism of the nonenzymatic endoperoxide forming cascade reaction that converts the precursor, dihydroartemisinic acid, to artemisinin in four steps: (i) first oxygen incorporation, (ii) C-C bond cleavage, (iii) second oxygen incorporation, (iv) and polycyclization to form artemisinin (1,2). Analogs of DHAA have been synthesized to probe endoperoxide formation, which led to the elucidation of the mechanism of the formation of the aromatic ring in serrulatene, an antibiotic plant natural product (3).

Secondly, human cytochrome P450 8B1, the oxysterol-12a-hydroxylase enzyme implicated in bile acid biosynthesis, is a therapeutic target to treat obesity. Preliminary studies involving the synthesis of a rationally designed inhibitor of P450 8B1 through the incorporation of a C12-pyridine in the steroid backbone, will be discussed (4).

1.         Varela, K., Arman, H. D., and Yoshimoto, F. K. (2020) Synthesis of [3,3-²H₂]-Dihydroartemisinic Acid to Measure the Rate of Nonenzymatic Conversion of Dihydroartemisinic Acid to Artemisinin. J. Nat. Prod. 83, 66-78

2.         Varela, K., Arman, H. D., and Yoshimoto, F. K. (2021) Synthesis of [15,15,15-²H₃]-Dihydroartemisinic Acid and Isotope Studies Support a Mixed Mechanism in the Endoperoxide Formation to Artemisinin J. Nat. Prod. 84, 1967-1984

3.         Varela, K., Al Mahmud, H., Arman, H. D., Martinez, L. R., Wakeman, C. A., and Yoshimoto, F. K. (2022) Autoxidation of a C2-Olefinated Dihydroartemisinic Acid Analogue to Form an Aromatic Ring: Application to Serrulatene Biosynthesis. J. Nat. Prod. 85, 951-962

4.         Chung, E., Offei, S. D., Jia, U. A., Estevez, J., Perez, Y., Arman, H. D., and Yoshimoto, F. K. (2022) A synthesis of a rationally designed inhibitor of cytochrome P450 8B1, a therapeutic target to treat obesity. Steroids 178, 108952

Dr. Michele Di Pierro  Di Pierro Lab

Abstract:

The human genome is composed of 46 DNA molecules — the chromosomes — with a combined length of about two meters. Chromosomes are stored in the cell nucleus in a very organized fashion that is specific to the cell type and phase of life; this three-dimensional architecture is a key element of transcriptional regulation and its disruption often leads to disease.  What is the physical mechanism leading to genome architecture? If the DNA contained in every human cell is identical, where is the blueprint of such architecture stored? 

In this talk, I will demonstrate how the architecture of interphase chromosomes is encoded in the one-dimensional sequence of epigenetic markings much as three-dimensional protein structures are determined by their one-dimensional sequence of amino acids. In contrast to the situation for proteins, however, the sequence code provided by the epigenetic marks that decorate the chromatin fiber is not fixed but is dynamically rewritten during cell differentiation, modulating both the three-dimensional structure and gene expression in different cell types.

This idea led to the development of a physical theory for the folding of genomes, which enables predicting the spatial conformation of chromosomes with unprecedented accuracy and specificity. Finally, I will demonstrate how the different energy terms present in our model impact the topology of chromosomes across evolution. Our results open the way for studying functional aspects of genome architecture along the three of life.

Bio:

Michele Di Pierro is Assistant Professor of Physics at Northeastern University and senior investigator of the Center for Theoretical Biological Physics — an NSF Frontier of Physics Center. He studied Condensed Matter Physics at the University of Rome “La Sapienza” and received a PhD in Applied Mathematics from The University of Texas at Austin. Prior to joining Northeastern University, he was the Robert A. Welch Postdoctoral Fellow at Rice University.

His research focuses on the physical processes involved in the translation of genetic information, a branch of biophysics which he refers to as Physical Genetics. His group develops novel theoretical approaches to characterize the structure and function of the genome using the tools of statistical physics, information theory, and computational modeling.

Dr. Christopher Hendon

Hendon Research

Biosketch: Christopher H. Hendon is an Assistant Professor of Computational Chemistry at the University of Oregon, with interests in energy materials and coffee extraction. He obtained his BSc. Adv. HONS from Monash University (2011) and PhD from the University of Bath (2015). After a two year postdoc at Massachusetts Institute of Technology he joined the University of where his research group focuses the chemistry of transition metal clusters.

Prof. Hendon’s interest in coffee began during his PhD, and since  then has published several peer-reviewed articles and a book, Water For Coffee. He enjoys washed African coffees, dry rieslings, and east coast oysters.

Abstract: Although generally thought of as highly ordered crystals, all metal-organic frameworks contain defects. Some defects may reveal catalytic active sites or hint at competing material phases, while othersmay result in electronic doping. Modern computational approaches are well-suited to studying theemergent chemistry of these imperfections, and can be used to directly inform experiment and characterization of materials with properties that diverge from those gleaned from crystallography. This talk discusses the chemistry afforded by defects in metal-organic frameworks, with a focus on structural dynamics and adatoms, both promoted by Lewis basic sites within the scaffolds. The utility of these defects will be presented from the perspective of heterogeneous catalyst development.

This lecture series commemorates the life and legacy of Professor Susan Odom, an energetic, productive, and driven faculty member in the Department of Chemistry from 2011 to 2021. It features speakers noted for outstanding research in Professor Odom’s fields of synthetic and materials chemistry.

Visit this page for more information on the Susan A. Odom lecture series.

Dr. Ellen Matson