Katherine Franz

Last updated
Katherine Jennings Franz
Alma mater Wellesley College
Massachusetts Institute of Technology
Scientific career
Institutions Duke University
Thesis Nitric oxide reactivity of manganese, iron and cobalt tropocoronands and development of fluorescent aminotroponiminates for nitric oxide sensing  (2000)

Katherine J. Franz (born 1972) is the chair of the department of chemistry at Duke University. She studies metal ion coordination in biological systems and looks to use the insight to manage species such as copper and iron. Franz was awarded the American Chemical Society Award for Encouraging Women into Careers in the Chemical Sciences.

Contents

Early life and education

Franz studied at Wellesley College and earned her bachelor's degree in 1995. [1] She was a member of the Wellesley College cross country team. [2] She moved to Massachusetts Institute of Technology for her graduate studies, where she worked under the supervision of Stephen J. Lippard and completed her PhD in 2001. [1] Her research considered the nitric oxide reactivity of manganese, iron and cobalt tropocoronand ligands. [3] She was an National Institutes of Health postdoctoral fellow from 2000 to 2003. [1]

Research and career

Franz became an assistant professor at Duke University in 2003. [1] She is an Associate member of the Duke Cancer Institute. [4] In 2005 Franz was awarded an National Science Foundation CAREER Award. She was made a Sloan Research Fellow in 2008 and promoted to professor in 2015. [1]

Franz has investigated the use of cellular metals in antimicrobial resistance. For example, by disrupting the amount of iron in a cell it is possible to withhold an essential pathogen, limiting the growth of microbes. On the other hand, copper can be used to control the growth of microbes, and immune cells appear to move copper to kill pathogens. At the same time, pathogens try to use copper to enhance their resistance and likelihood of survival. Franz attempts to use copper in the same way as biological systems to target antimicrobial agents. [5] She has looked at iron and copper as ionophores; which are important in the virulence of Cryptococcus neoformans . [6]

Franz also works on anti-cancer prochelators; molecules that do not have much affinity for metal ions, but can be triggered until they undergo a chemical conversion. Cancer cells have different metallomes than normal cells. For example, prostate cancer results in the overexpression of copper trafficking proteins, causing a high level of copper. She looks to target these copper ions by creating prochelators that become activated in the microenvironment of cancer. [6] Gamma-glutamyltransferase is an enzyme that is overexpressed in cancer, and releases the chelator dithiocarbamate from the prochelator developed by Franz's research group, which forms a toxic copper complex. [6] [7] She works on iron chelators that can be used to remove deleterious iron in brain regions impacted by Parkinson's disease without damaging the healthy metal ions. The chelators developed by Franz have no affinity for iron until a mask is released by hydrogen peroxide, releasing a reactive oxygen species that combines with iron to form hydroxyl radicals. [6] Additionally Franz studies copper-binding peptides such as histatin. Histatin binds to copper in vitro, but it is not clear how they interact or how the anti-fungal activity is modified. The Franz group have studied the anti-fungal activity of Histatin-5 against Candida albicans . [6] [8]

Academic service

Alongside her academic research, Franz is committed to mentoring early career researchers. [9] She was awarded the Duke University Dean's Award for Excellence in Mentoring in 2016. [10] In 2019 Franz was awarded the American Chemical Society Award for Encouraging Women into Careers in the Chemical Sciences. [11]

Franz co-edited the American Chemical Society Metals in Medicine Chemical Reviews. [12] Franz was made the chair of the Gordon Research Conference on Metals in Medicine in 2013.

Selected publications

Her publications include;

Related Research Articles

<span class="mw-page-title-main">Redox</span> Chemical reaction in which oxidation states of atoms are changed

Redox is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a decrease in the oxidation state. The oxidation and reduction processes occur simultaneously in the chemical reaction.

Chelation is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate ligand and a single central metal atom. These ligands are called chelants, chelators, chelating agents, or sequestering agents. They are usually organic compounds, but this is not a necessity.

<span class="mw-page-title-main">Nitric oxide</span> Colorless gas with the formula NO

Nitric oxide is a colorless gas with the formula NO. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula. Nitric oxide is also a heteronuclear diatomic molecule, a class of molecules whose study spawned early modern theories of chemical bonding.

In chemistry, a reactivity series (or reactivity series of elements) is an empirical, calculated, and structurally analytical progression of a series of metals, arranged by their "reactivity" from highest to lowest. It is used to summarize information about the reactions of metals with acids and water, single displacement reactions and the extraction of metals from their ores.

<span class="mw-page-title-main">Siderophore</span> Iron compounds secreted by microorganisms

Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is now being appreciated, siderophores are among the strongest (highest affinity) Fe3+ binding agents known. Phytosiderophores are siderophores produced by plants.

Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well as artificially introduced metals, including those that are non-essential, in medicine and toxicology. Many biological processes such as respiration depend upon molecules that fall within the realm of inorganic chemistry. The discipline also includes the study of inorganic models or mimics that imitate the behaviour of metalloproteins.

<span class="mw-page-title-main">Ionophore</span> Chemical entity that reversibly binds ions

In chemistry, an ionophore is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liquid polymeric membranes or lipid bilayers found in the living cells or synthetic vesicles (liposomes). Structurally, an ionophore contains a hydrophilic center and a hydrophobic portion that interacts with the membrane.

<span class="mw-page-title-main">Nitrosation and nitrosylation</span> Process of converting organic compounds into nitroso derivatives

Nitrosation and nitrosylation are two names for the process of converting organic compounds or metal complexes into nitroso derivatives, i.e., compounds containing the R−NO functionality. The synonymy arises because the R-NO functionality can be interpreted two different ways, depending on the physico-chemical environment:

<span class="mw-page-title-main">Nitroxyl</span> Chemical compound

Nitroxyl or azanone is the chemical compound HNO. It is well known in the gas phase. Nitroxyl can be formed as a short-lived intermediate in the solution phase. The conjugate base, NO−, nitroxide anion, is the reduced form of nitric oxide (NO) and is isoelectronic with dioxygen. The bond dissociation energy of H−NO is 49.5 kcal/mol (207 kJ/mol), which is unusually weak for a bond to the hydrogen atom.

<span class="mw-page-title-main">Pentetic acid</span> DTPA: aminopolycarboxylic acid

Pentetic acid or diethylenetriaminepentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a diethylenetriamine backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of EDTA and is used similarly. It is a white solid with limited solubility in water.

<span class="mw-page-title-main">Sodium diethyldithiocarbamate</span> Chemical compound

Sodium diethyldithiocarbamate is the organosulfur compound with the formula NaS2CN(C2H5)2. It is a pale yellow, water soluble salt.

Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example, an overdose of the analgesic paracetamol (acetaminophen) can fatally damage the liver, partly through its production of reactive oxygen species.

<span class="mw-page-title-main">Radical (chemistry)</span> Atom, molecule, or ion that has an unpaired valence electron; typically highly reactive

In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spontaneously dimerize. Most organic radicals have short lifetimes.

Histatins are histidine-rich (cationic) antimicrobial proteins found in saliva. Histatin's involvement in antimicrobial activities makes histatin part of the innate immune system.

<span class="mw-page-title-main">Pyrrolidine dithiocarbamate</span> Chemical compound

Pyrrolidine dithiocarbamate (PDTC) are a family of closely related drugs used for a metal chelation, induction of G1 phase cell cycle arrest, and preventing induction of nitric oxide synthase.

<span class="mw-page-title-main">Stephen J. Lippard</span> American chemist

Stephen James Lippard is the Arthur Amos Noyes Emeritus Professor of Chemistry at the Massachusetts Institute of Technology. He is considered one of the founders of bioinorganic chemistry, studying the interactions of nonliving substances such as metals with biological systems. He is also considered a founder of metalloneurochemistry, the study of metal ions and their effects in the brain and nervous system. He has done pioneering work in understanding protein structure and synthesis, the enzymatic functions of methane monooxygenase (MMO), and the mechanisms of cisplatin anticancer drugs. His work has applications for the treatment of cancer, for bioremediation of the environment, and for the development of synthetic methanol-based fuels.

<span class="mw-page-title-main">TPEN</span> Chemical compound

TPEN (N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine) is an intracellular membrane-permeable ion chelator. TPEN has a high affinity for many transition metals and should not be considered specific or selective for a particular ion. Chelators can be used in chelation therapy to remove toxic metals in the body. TPEN is a chelator that has a high affinity for zinc. For example, one study showed that TPEN is a stronger chelator compared to other chelators like pentetic acid (DTPA) when high levels of zinc are present (15 μM). When low levels of zinc were present however (0, 3, 6, 9 and 12 μM zinc), there was no significant difference. TPEN is a hexadentate ligand which also forms complexes with other soft metal ions such as Cd2+.

<span class="mw-page-title-main">Transition metal dithiocarbamate complexes</span>

Transition metal dithiocarbamate complexes are coordination complexes containing one or more dithiocarbamate ligand, which are typically abbreviated R2dtc−. Many complexes are known. Several homoleptic derivatives have the formula M(R2dtc)n where n = 2 and 3.

Kay Michille Brummond is an American synthetic chemist who is Professor of Chemistry and Associate Dean of Faculty at the University of Pittsburgh. Her interests consider cycloaddition reactions that can realise molecules and natural products for organic photovoltaics and targeted covalent inhibitors. She was elected a Fellow of the American Chemical Society (ACS) in 2010, a Fellow of the AAAS in 2021, and awarded the ACS National Award for Encouraging Women into Careers in the Chemical Sciences in 2021.

Metallopeptides are peptides that contain one or more metal ions in their structure. This specific type of peptide are, just like metalloproteins, metallofoldamers. And very similar to metalloproteins, metallopeptide's functionality is attributed through the contained metal ion cofactor. These short structured peptides are often employed to develop mimics of metalloproteins and systems similar to artificial metalloenzymes.

References

  1. 1 2 3 4 5 "People – The Franz Lab" . Retrieved 2019-08-27.
  2. ↑ "NEWMAC". NEWMAC. Retrieved 2019-08-27.
  3. ↑ Franz, Katherine J. (Katherine Jennings) (2000). Nitric oxide reactivity of manganese, iron and cobalt tropocoronands and development of fluorescent aminotroponiminates for nitric oxide sensing (Thesis thesis). Massachusetts Institute of Technology. hdl: 1721.1/29590 .
  4. ↑ "Franz, Katherine J." Duke Cancer Institute. 2016-12-20. Retrieved 2019-08-27.
  5. ↑ "Dr. Katherine J. Franz - Department of Chemistry & Biochemistry - UMBC". chemistry.umbc.edu. Retrieved 2019-08-27.
  6. 1 2 3 4 5 "Research – The Franz Lab" . Retrieved 2019-08-27.
  7. ↑ Bakthavatsalam S, Sleeper ML, Dharani A, George DJ, Zhang T, Franz KJ (September 2018). "Leveraging γ-Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells". Angewandte Chemie. 57 (39): 12780–12784. doi:10.1002/anie.201807582. PMC   6372289 . PMID   30025197.
  8. ↑ Conklin SE, Bridgman EC, Su Q, Riggs-Gelasco P, Haas KL, Franz KJ (August 2017). "Specific Histidine Residues Confer Histatin Peptides with Copper-Dependent Activity against Candida albicans". Biochemistry. 56 (32): 4244–4255. doi:10.1021/acs.biochem.7b00348. PMC   5937946 . PMID   28763199.
  9. ↑ Having Multiple Mentors: Katherine J. Franz, 18 March 2016, retrieved 2019-08-27
  10. ↑ "Katherine J. Franz, 2016 Dean's Award Winner | Duke Graduate School". gradschool.duke.edu. Retrieved 2019-08-27.
  11. ↑ "ACS 2020 national award winners". Chemical & Engineering News. Retrieved 2019-08-27.
  12. ↑ "Chemical Reviews | Vol 119, No 2". pubs.acs.org. Retrieved 2019-08-27.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.