Brent Stockwell | |
---|---|
Born | Bay Terrace, Queens, New York, US |
Known for | discovering Ferroptosis |
Spouse | Melissa Stockwell (m. 2000) |
Awards | Beckman Young Investigators Award |
Academic background | |
Education | AB, chemistry and economics, Cornell University PhD, 1999, Harvard University |
Thesis | Forward and reverse chemical genetic studies of transforming growth factor beta signaling (1999) |
Academic work | |
Institutions | Columbia University Whitehead Institute Harvard University |
Website | stockwelllab |
Brent Roark Stockwell is an American chemical biologist. He is a Professor of Biological Sciences and Chemistry at Columbia University. In 2012,Stockwell and Scott Dixon coined the term ferroptosis and described several of its key features.
Stockwell was born in Bay Terrace,New York and attended Hunter College High School. He received his undergraduate degree in chemistry and economics from Cornell University and his Ph.D. in chemistry at Harvard University. [1] While completing his doctorate degree,Stockwell worked in the laboratory of Stuart Schreiber where he spent eighteen months unsuccessfully investigating a molecule that could shut down the protein TGF-beta. He eventually used naturally occurring molecules to block the effects of TGF-beta,resulting in the discovery that synthetic molecules were unlikely to be successful drug candidates. [2] As a result of his research,Stockwell founded CombinatoRx to develop combinations of FDA-approved drugs to fight disease. [3]
Following his PhD,Stockwell was appointed as a Whitehead Fellow at the Whitehead Institute,where he worked on synthetic lethal screens and cell death. In 2003,he developed the first library of biologically annotated compounds and approved drugs to capture the information underlying cellular mechanisms to give scientists greater and more immediate insight into cell biology mechanisms. [4] [5] He also began a campaign to identify compounds that selectively kill engineered tumor cells,identifying and naming the novel compound erastin. [6]
Upon completing his fellowship,Stockwell joined the faculty at Columbia University as an assistant professor of biological sciences and of chemistry. Early into his tenure at the institution,Stockwell found two new compounds,RSL3 and RSL5,that could kill tumor cells. [7] In order to find drug candidates that could selectively kill tumor cells,Stockwell used cells engineered with a cancer-causing mutation and identical cells lacking the mutation. [3] As a result of his research into undiscovered mechanisms controlling cell death,Stockwell received a 2007 Beckman Young Investigators Award [8] and was named a 2009 Howard Hughes Medical Institute Early Career Scientist. [3] Following this,he was one of six winners of the BioAccelerate NYC Prize to conduct late-stage,"proof-of-concept" research on a new class of drugs to treat cancer in a more selective and non-toxic way. [9]
In 2011,Stockwell published his first book entitled The Quest for the Cure:The Science and Stories Behind the Next Generation of Medicine. [10] [11] Later,using erastin,Stockwell discovered the process of ferroptosis,coined the term ferroptosis,described its key mechanisms,and developed the first chemical probes to control ferroptosis. [12] In 2014,he received one of 10 recipients of the 2014 Lenfest Distinguished Teaching Awards. [13]
During the COVID-19 pandemic,Stockwell co-published Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors through the journal Nature Communications . [14] He was also recognized by City &State as one of the inaugural Life Sciences Power 50 amongst scientists,entrepreneurs and investors. [15] Later in November,Stockwell was again listed by Clarivate as one of the Highly Cited Researchers of the Year. [16]
In 2023,Stockwell was elected to the National Academy of Medicine. [17]
Stockwell is married to Melissa,an Associate Professor of Pediatrics and Population and Family Health at Columbia. [18] Stockwell has two sons. [19]
Cyclooxygenase-2 inhibitors,also known as coxibs,are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2 (COX-2),an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib,rofecoxib,and other members of this drug class.
Cisplatin is a chemical compound with formula cis-[Pt(NH3)2Cl2]. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer,ovarian cancer,cervical cancer,bladder cancer,head and neck cancer,esophageal cancer,lung cancer,mesothelioma,brain tumors and neuroblastoma. It is given by injection into a vein.
Bufagin is a toxic steroid C24H34O5 obtained from toad's milk,the poisonous secretion of a skin gland on the back of the neck of a large toad (Rhinella marina,synonym Bufo marinus,the cane toad). The toad produces this secretion when it is injured,scared or provoked. Bufagin resembles chemical substances from digitalis in physiological activity and chemical structure.
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.
Nanobiotechnology,bionanotechnology,and nanobiology are terms that refer to the intersection of nanotechnology and biology. Given that the subject is one that has only emerged very recently,bionanotechnology and nanobiotechnology serve as blanket terms for various related technologies.
Photosensitizers are light absorbers that alter the course of a photochemical reaction. They usually are catalysts. They can function by many mechanisms,sometimes they donate an electron to the substrate,sometimes they abstract a hydrogen atom from the substrate. At the end of this process,the photosensitizer returns to its ground state,where it remains chemically intact,poised to absorb more light. One branch of chemistry which frequently utilizes photosensitizers is polymer chemistry,using photosensitizers in reactions such as photopolymerization,photocrosslinking,and photodegradation. Photosensitizers are also used to generate prolonged excited electronic states in organic molecules with uses in photocatalysis,photon upconversion and photodynamic therapy. Generally,photosensitizers absorb electromagnetic radiation consisting of infrared radiation,visible light radiation,and ultraviolet radiation and transfer absorbed energy into neighboring molecules. This absorption of light is made possible by photosensitizers' large de-localized π-systems,which lowers the energy of HOMO and LUMO orbitals to promote photoexcitation. While many photosensitizers are organic or organometallic compounds,there are also examples of using semiconductor quantum dots as photosensitizers.
Stuart Schreiber is an American chemist who is the Morris Loeb Research Professor at Harvard University,a co-founder of the Broad Institute,Howard Hughes Medical Institute Investigator,Emeritus,and a member of the National Academy of Sciences and National Academy of Medicine. He currently leads Arena BioWorks.
Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral,antimalarial,and anti-inflammatory properties,as well as a more recently discovered potential as an anticancer agent,by inhibition of topoisomerase. It is found in the bark of several species of plants,principally the white birch from which it gets its name,same as the bracket fungus Fomitopsis betulina,but also the ber tree,selfheal,the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus,Diospyros leucomelas,a member of the persimmon family,Tetracera boiviniana,the jambul,flowering quince,rosemary,and Pulsatilla chinensis.
Joanna Sigfred Fowler is a scientist emeritus at the U.S. Department of Energy's Brookhaven National Laboratory in New York. She served as professor of psychiatry at Mount Sinai School of Medicine and director of Brookhaven's Radiotracer Chemistry,Instrumentation and Biological Imaging Program. Fowler studied the effect of disease,drugs,and aging on the human brain and radiotracers in brain chemistry. She has received many awards for her pioneering work,including the National Medal of Science.
Alexander Levitzki is an Israeli biochemist who is a professor of biochemistry at the Alexander Silberman Institute of Life Sciences,the Hebrew University of Jerusalem.
Cystine/glutamate transporter is an antiporter that in humans is encoded by the SLC7A11 gene.
Peter S. Kim is an American scientist. He was president of Merck Research Laboratories (MRL) 2003–2013 and is currently Virginia &D.K. Ludwig Professor of Biochemistry at Stanford University,Institute Scholar at Stanford ChEM-H,and Lead Investigator of the Infectious Disease Initiative at the Chan Zuckerberg Biohub.
Panobinostat,sold under the brand name Farydak,is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor.
Salinomycin is an antibacterial and coccidiostat ionophore therapeutic drug.
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.
Ming-Ming Zhou is an American scientist whose specification is structural and chemical biology,NMR spectroscopy,and drug design. He is the Dr. Harold and Golden Lamport Professor and Chairman of the Department of Pharmacological Sciences. He is also the co-director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai and Mount Sinai Health System in New York City,as well as Professor of Sciences. Zhou is an elected fellow of the American Association for the Advancement of Science.
mTOR inhibitors are a class of drugs used to treat several human diseases,including cancer,autoimmune diseases,and neurodegeneration. They function by inhibiting the mammalian target of rapamycin (mTOR),which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism,growth,and proliferation by forming and signaling through two protein complexes,mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs,which have shown tumor responses in clinical trials against various tumor types.
Oxytosis/ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides,and is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis. Oxytosis/ferroptosis is initiated by the failure of the glutathione-dependent antioxidant defenses,resulting in unchecked lipid peroxidation and eventual cell death. Lipophilic antioxidants and iron chelators can prevent ferroptotic cell death. Although the connection between iron and lipid peroxidation has been appreciated for years,it was not until 2012 that Brent Stockwell and Scott J. Dixon coined the term ferroptosis and described several of its key features. Pamela Maher and David Schubert discovered the process in 2001 and called it oxytosis. While they did not describe the involvement of iron at the time,oxytosis and ferroptosis are today thought to be the same cell death mechanism.
György Kéri was a Hungarian biochemist,professor and Doctor of Biological Sciences (D.Sc.). His major field of research was signal transduction therapy and he participated in the development of novel drug discovery technologies and drug candidates that entered the clinical development process.
Erastin is a small molecule capable of initiating ferroptotic cell death. Erastin binds and activates voltage-dependent anion channels (VDAC) by reversing tubulin's inhibition on VDAC2 and VDAC3,and functionally inhibits the cystine-glutamate antiporter system Xc−. Cells treated with erastin are deprived of cysteine and are unable to synthesize the antioxidant glutathione. Depletion of glutathione eventually leads to excessive lipid peroxidation and cell death.
Brent Stockwell publications indexed by Google Scholar