Eli Chapman

Eli Chapman, Ph.D.

Professor

Department: MD-PHARMACOLOGY / THERAPEUTICS
Business Phone: (561) 228-2559
Business Email: chapmaneli@ufl.edu

About Eli Chapman

Dr. Chapman is a professor at the University of Florida in the Department of Pharmacology and Therapeutics and the Center for Inflammation Science and Systems Medicine (CISSM). He began his scientific career at UC Berkeley, working for Prof. Peter G. Schultz. In the Schultz lab, he worked on in vitro incorporation of unnatural amino acids into proteins. The primary focus of these projects was to understand how hydrogen bonding contributed to protein stability. From UC Berkely, he went to Columbia University and joined the lab of Prof. James Leighton. In the Leighton lab, he developed a rhodium catalyzed silylformylation of alkenes as an entry into 1,3-polyols. He received a master’s from Columbia and then joined the lab of Prof. Chi-Huey Wong at The Scripps Research Institute (TSRI) to complete his Ph.D. studies. In the Wong lab, he worked on biological sulfation and how to inhibit sulfotransferases. During this time, he became interested in cellular quality control, especially in the context of protein folding in a cell or organism. This curiosity led him to the lab of Prof. Arthur Horwich at Yale College of Medicine. It was in the Horwich lab that he began developing small molecule inhibitors of GroEL/ES as probes to study chaperonin physiologic action and as potential therapeutic leads. In 2012, he began his independent career at the University of Arizona. His lab has been focused on compound discovery and development primarily centered around cellular quality control. The Chapman lab has made important discoveries in the areas of HSP60/10 (GroEL/ES), HSP70, and NRF2. To date, he has trained 5 Ph.D. students and numerous master’s and undergraduate students. He has published over 90 peer-reviewed papers and holds four patents and six additional provisional patents. In 2024, he joined the University of Florida where he works at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology in the CISSM.

Teaching Profile

Courses Taught
2025
GMS6009 Principles of Drug Action and Therapeutics
2025
GMS6560 Molecules to Man: Past, Present and Future Therapeutic Strategies for Disease

Research Profile

The Chapman Lab is a chemical biology lab that focuses on the discovery and development of small-molecule modulators of cellular quality control machinery. These compounds are used to answer biological questions, to validate potential therapeutic targets, and as possible therapeutic leads. There are three primary areas of focus: 1) The discovery and development of isoform selective HSP70 inhibitors as potential cancer therapeutics. 2) The development of HSP60/10 inhibitors as cancer therapeutics and GroEL/ES (the bacterial HSP60/10) inhibitors as antibiotics. 3) The discovery and development of NRF2 activators as chemopreventive compounds and NRF2 inhibitors as cancer therapeutics.

The HSP70 chaperones have been shown to be upregulated in a variety of cancers and to correlate with poor outcomes. They have, therefore, been proposed as potential drug targets. However, there are 13 HSP70 isoforms in the human body and it has been shown that there are clear advantages to being able to target one isoform selectively. We have recently reported the discovery and development of compounds with isoform selectivity. We continue to develop these compounds, striving to increase selectivity, potency, and bioavailability.

About 10 years ago, we reported a high-throughput screening campaign to discover GroEL/ES inhibitors. We have gone on to optimize some of these scaffolds, demonstrating their potential as antibiotics especially against MRSA. We have also begun exploring the human HSP60/10 chaperone system as a potential anti-cancer therapy. These latter studies will help to define HSP60/10 as a potential cancer target and the role of extracellular HSP60/10 in inflammation.

In collaboration with the lab of Dr. Donna Zhang, we have been working to discovery activators and inhibitors of the cytoprotective transcription factor NRF2. NRF2 has long played a role in the chemoprevention field, where it has been shown that activation of NRF2 confers protection against cellular insults. But, it has been shown that many cancers have upregulated NRF2, conferring a survival advantage. Therefore, we have been working to discover and develop compounds that directly target NRF2 and block its protective functions.

Areas of Interest
  • Cellular quality control
  • Chaperones
  • Chemical biology
  • Drug discovery

Publications

Academic Articles
2025
Pharmacological Modulation of the Unfolded Protein Response as a Therapeutic Approach in Cutaneous T-Cell Lymphoma
Biomolecules. 15(1) [DOI] 10.3390/biom15010076. [PMID] 39858470.
2024
Bis-sulfonamido-2-phenylbenzoxazoles Validate the GroES/EL Chaperone System as a Viable Antibiotic Target.
Journal of the American Chemical Society. 146(30):20845-20856 [DOI] 10.1021/jacs.4c05057. [PMID] 39041457.
2024
Human Hsp70 Substrate-Binding Domains Recognize Distinct Client Proteins.
Biochemistry. 63(3):251-263 [DOI] 10.1021/acs.biochem.3c00531. [PMID] 38243804.
2024
Lactoylglutathione promotes inflammatory signaling in macrophages through histone lactoylation.
Molecular metabolism. 81 [DOI] 10.1016/j.molmet.2024.101888. [PMID] 38307385.
2024
Stimulus-related oscillatory brain activity discriminates hoarding disorder from OCD and healthy controls.
Biological psychology. 192 [DOI] 10.1016/j.biopsycho.2024.108848. [PMID] 39048018.
2023
Anti-Ferroptotic Effects of Nrf2: Beyond the Antioxidant Response.
Molecules and cells. 46(3):165-175 [DOI] 10.14348/molcells.2023.0005. [PMID] 36994475.
2023
Decreased autophagosome biogenesis, reduced NRF2, and enhanced ferroptotic cell death are underlying molecular mechanisms of non-alcoholic fatty liver disease.
Redox biology. 59 [DOI] 10.1016/j.redox.2022.102570. [PMID] 36495698.
2023
Discovery and Development of a Selective Inhibitor of the ER Resident Chaperone Grp78.
Journal of medicinal chemistry. 66(1):677-694 [DOI] 10.1021/acs.jmedchem.2c01631. [PMID] 36516003.
2023
Lactoylglutathione promotes inflammatory signaling in macrophages.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2023.10.10.561739. [PMID] 37873172.
2023
NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8.
Science advances. 9(5) [DOI] 10.1126/sciadv.ade9585. [PMID] 36724221.
2023
Physachenolide C is a Potent, Selective BET Inhibitor.
Journal of medicinal chemistry. 66(1):913-933 [DOI] 10.1021/acs.jmedchem.2c01770. [PMID] 36577036.
2023
The NRF2-p97-NRF2 negative feedback loop.
Redox biology. 65 [DOI] 10.1016/j.redox.2023.102839. [PMID] 37573837.
2022
Allosteric differences dictate GroEL complementation of E. coli.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 36(3) [DOI] 10.1096/fj.202101708RR. [PMID] 35199390.
2022
Bis-aryl-α,β-unsaturated ketone (ABK) chaperonin inhibitors exhibit selective cytotoxicity to colorectal cancer cells that correlates with levels of aberrant HSP60 in the cytosol.
Bioorganic & medicinal chemistry. 75 [DOI] 10.1016/j.bmc.2022.117072. [PMID] 36356534.
2022
CHML is an NRF2 target gene that regulates mTOR function.
Molecular oncology. 16(8):1714-1727 [DOI] 10.1002/1878-0261.13194. [PMID] 35184380.
2021
A two-step resin based approach to reveal survivin-selective fluorescent probes.
RSC chemical biology. 2(1):181-186 [DOI] 10.1039/d0cb00122h. [PMID] 34458780.
2021
Discovery of an eIF4A Inhibitor with a Novel Mechanism of Action.
Journal of medicinal chemistry. 64(21):15727-15746 [DOI] 10.1021/acs.jmedchem.1c01014. [PMID] 34676755.
2021
Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer.
Bioorganic & medicinal chemistry. 40 [DOI] 10.1016/j.bmc.2021.116129. [PMID] 33971488.
2021
FAM129B-dependent activation of NRF2 promotes an invasive phenotype in BRAF mutant melanoma cells.
Molecular carcinogenesis. 60(5):331-341 [DOI] 10.1002/mc.23295. [PMID] 33684228.
2021
Function, Therapeutic Potential, and Inhibition of Hsp70 Chaperones.
Journal of medicinal chemistry. 64(11):7060-7082 [DOI] 10.1021/acs.jmedchem.0c02091. [PMID] 34009983.
2021
Functional Differences between E. coli and ESKAPE Pathogen GroES/GroEL.
mBio. 12(1) [DOI] 10.1128/mBio.02167-20. [PMID] 33436430.
2021
Molecular Dynamics Simulations Identify Tractable Lead-like Phenyl-Piperazine Scaffolds as eIF4A1 ATP-competitive Inhibitors.
ACS omega. 6(38):24432-24443 [DOI] 10.1021/acsomega.1c02805. [PMID] 34604625.
2021
Non-canonical NRF2 activation promotes a pro-diabetic shift in hepatic glucose metabolism.
Molecular metabolism. 51 [DOI] 10.1016/j.molmet.2021.101243. [PMID] 33933676.
2021
Sirtuin 2 Regulates Protein LactoylLys Modifications.
Chembiochem : a European journal of chemical biology. 22(12):2102-2106 [DOI] 10.1002/cbic.202000883. [PMID] 33725370.
2021
Targeting NRF2 to treat cancer.
Seminars in cancer biology. 76:61-73 [DOI] 10.1016/j.semcancer.2021.06.003. [PMID] 34102289.
2021
The intricacies of NRF2 regulation in cancer.
Seminars in cancer biology. 76:110-119 [DOI] 10.1016/j.semcancer.2021.05.016. [PMID] 34020028.
2021
The NRF2-LOC344887 signaling axis suppresses pulmonary fibrosis.
Redox biology. 38 [DOI] 10.1016/j.redox.2020.101766. [PMID] 33126057.
2021
UniDecCD: Deconvolution of Charge Detection-Mass Spectrometry Data.
Analytical chemistry. 93(44):14722-14729 [DOI] 10.1021/acs.analchem.1c03181. [PMID] 34705424.
2020
Analogs of nitrofuran antibiotics are potent GroEL/ES inhibitor pro-drugs.
Bioorganic & medicinal chemistry. 28(22) [DOI] 10.1016/j.bmc.2020.115710. [PMID] 33007545.
2020
Chronic arsenic exposure enhances metastatic potential via NRF2-mediated upregulation of SOX9.
Toxicology and applied pharmacology. 402 [DOI] 10.1016/j.taap.2020.115138. [PMID] 32682831.
2020
Non-enzymatic Lysine Lactoylation of Glycolytic Enzymes.
Cell chemical biology. 27(2):206-213.e6 [DOI] 10.1016/j.chembiol.2019.11.005. [PMID] 31767537.
2020
NRF2 negatively regulates primary ciliogenesis and hedgehog signaling
PLOS Biology. 18(2) [DOI] 10.1371/journal.pbio.3000620. [PMID] 32053600.
2020
The role of natural products in revealing NRF2 function.
Natural product reports. 37(6):797-826 [DOI] 10.1039/c9np00061e. [PMID] 32400766.
2019
A high throughput substrate binding assay reveals hexachlorophene as an inhibitor of the ER-resident HSP70 chaperone GRP78.
Bioorganic & medicinal chemistry letters. 29(14):1689-1693 [DOI] 10.1016/j.bmcl.2019.05.041. [PMID] 31129054.
2019
A one-step, atom economical synthesis of thieno[2,3-d]pyrimidin-4-amine derivatives via a four-component reaction.
European journal of organic chemistry. 20(2):3269-3272 [DOI] 10.1002/ejoc.201900414. [PMID] 31857792.
2019
An Isoform-Selective PTP1B Inhibitor Derived from Nitrogen-Atom Augmentation of Radicicol.
Biochemistry. 58(30):3225-3231 [DOI] 10.1021/acs.biochem.9b00499. [PMID] 31298844.
2019
Catalytic asymmetric synthesis of 2,5-dihydrofurans using synergistic bifunctional Ag catalysis.
Organic & biomolecular chemistry. 17(38):8737-8744 [DOI] 10.1039/c9ob01903k. [PMID] 31553003.
2019
Dual-targeting GroEL/ES chaperonin and protein tyrosine phosphatase B (PtpB) inhibitors: A polypharmacology strategy for treating Mycobacterium tuberculosis infections.
Bioorganic & medicinal chemistry letters. 29(13):1665-1672 [DOI] 10.1016/j.bmcl.2019.04.034. [PMID] 31047750.
2019
HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules.
Bioorganic & medicinal chemistry letters. 29(9):1106-1112 [DOI] 10.1016/j.bmcl.2019.02.028. [PMID] 30852084.
2019
Modulating NRF2 in Disease: Timing Is Everything.
Annual review of pharmacology and toxicology. 59:555-575 [DOI] 10.1146/annurev-pharmtox-010818-021856. [PMID] 30256716.
2019
Non-covalent NRF2 Activation Confers Greater Cellular Protection than Covalent Activation.
Cell chemical biology. 26(10):1427-1435.e5 [DOI] 10.1016/j.chembiol.2019.07.011. [PMID] 31402317.
2019
One-Step Synthesis of Thieno[2,3-d]pyrimidin-4(3H)-ones via a Catalytic Four-Component Reaction of Ketones, Ethyl Cyanoacetate, S8 and Formamide.
ACS sustainable chemistry & engineering. 7(1):1524-1528 [DOI] 10.1021/acssuschemeng.8b05276. [PMID] 31754553.
2019
Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S-Mediated Noncanonical Mechanism.
Hepatology (Baltimore, Md.). 70(1):372-388 [DOI] 10.1002/hep.30616. [PMID] 30873635.
2018
A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B).
ACS chemical biology. 13(10):3000-3010 [DOI] 10.1021/acschembio.8b00745. [PMID] 30141626.
2018
Hydroxybiphenylamide GroEL/ES Inhibitors Are Potent Antibacterials against Planktonic and Biofilm Forms of Staphylococcus aureus.
Journal of medicinal chemistry. 61(23):10651-10664 [DOI] 10.1021/acs.jmedchem.8b01293. [PMID] 30392371.
2018
Increased O-GlcNAcylation of SNAP29 Drives Arsenic-Induced Autophagic Dysfunction.
Molecular and cellular biology. 38(11) [DOI] 10.1128/MCB.00595-17. [PMID] 29507186.
2018
Low-level arsenic causes proteotoxic stress and not oxidative stress.
Toxicology and applied pharmacology. 341:106-113 [DOI] 10.1016/j.taap.2018.01.014. [PMID] 29408041.
2018
NRF2 and the Hallmarks of Cancer.
Cancer cell. 34(1):21-43 [DOI] 10.1016/j.ccell.2018.03.022. [PMID] 29731393.
2018
Sulfonamido-2-arylbenzoxazole GroEL/ES Inhibitors as Potent Antibacterials against Methicillin-Resistant Staphylococcus aureus (MRSA).
Journal of medicinal chemistry. 61(16):7345-7357 [DOI] 10.1021/acs.jmedchem.8b00989. [PMID] 30060666.
2018
Target-Based Screening against eIF4A1 Reveals the Marine Natural Product Elatol as a Novel Inhibitor of Translation Initiation with In Vivo Antitumor Activity.
Clinical cancer research : an official journal of the American Association for Cancer Research. 24(17):4256-4270 [DOI] 10.1158/1078-0432.CCR-17-3645. [PMID] 29844128.
2018
The effects of NRF2 modulation on the initiation and progression of chemically and genetically induced lung cancer.
Molecular carcinogenesis. 57(2):182-192 [DOI] 10.1002/mc.22745. [PMID] 28976703.
2017
An epigenetic modifier induces production of (10’S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla.
Bioorganic & medicinal chemistry. 25(6):1860-1866 [DOI] 10.1016/j.bmc.2017.01.048. [PMID] 28202316.
2017
Arsenic Compromises Both p97 and Proteasome Functions.
Chemical research in toxicology. 30(7):1508-1514 [DOI] 10.1021/acs.chemrestox.7b00158. [PMID] 28636814.
2017
ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A.
Bioorganic & medicinal chemistry letters. 27(17):4082-4085 [DOI] 10.1016/j.bmcl.2017.07.045. [PMID] 28757063.
2017
Brusatol overcomes chemoresistance through inhibition of protein translation.
Molecular carcinogenesis. 56(5):1493-1500 [DOI] 10.1002/mc.22609. [PMID] 28019675.
2017
Chlorinated Dehydrocurvularins and Alterperylenepoxide A from Alternaria sp. AST0039, a Fungal Endophyte of Astragalus lentiginosus.
Journal of natural products. 80(2):427-433 [DOI] 10.1021/acs.jnatprod.6b00960. [PMID] 28139929.
2017
p97 Negatively Regulates NRF2 by Extracting Ubiquitylated NRF2 from the KEAP1-CUL3 E3 Complex.
Molecular and cellular biology. 37(8) [DOI] 10.1128/MCB.00660-16. [PMID] 28115426.
2017
Ritterostatin GN 1N , a Cephalostatin-Ritterazine Bis-steroidal Pyrazine Hybrid, Selectively Targets GRP78.
Chembiochem : a European journal of chemical biology. 18(6):506-510 [DOI] 10.1002/cbic.201600669. [PMID] 28074539.
2016
GroEL/ES inhibitors as potential antibiotics.
Bioorganic & medicinal chemistry letters. 26(13):3127-3134 [DOI] 10.1016/j.bmcl.2016.04.089. [PMID] 27184767.
2016
NRF2-targeted therapeutics: New targets and modes of NRF2 regulation.
Current opinion in toxicology. 1:62-70 [DOI] 10.1016/j.cotox.2016.10.005. [PMID] 29082352.
2016
Oxaspirol B with p97 Inhibitory Activity and Other Oxaspirols from Lecythophora sp. FL1375 and FL1031, Endolichenic Fungi Inhabiting Parmotrema tinctorum and Cladonia evansii.
Journal of natural products. 79(2):340-52 [DOI] 10.1021/acs.jnatprod.5b00986. [PMID] 26812276.
2016
Role of Nrf2 and Autophagy in Acute Lung Injury.
Current pharmacology reports. 2(2):91-101 [PMID] 27313980.
2016
Selective inhibition of p97 by chlorinated analogues of dehydrocurvularin.
Organic & biomolecular chemistry. 14(25):5918-21 [DOI] 10.1039/c6ob00560h. [PMID] 27223265.
2016
Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness.
Bioorganic & medicinal chemistry letters. 26(21):5247-5253 [DOI] 10.1016/j.bmcl.2016.09.051. [PMID] 27720295.
2015
A Curcumin Derivative That Inhibits Vinyl Carbamate-Induced Lung Carcinogenesis via Activation of the Nrf2 Protective Response.
Antioxidants & redox signaling. 23(8):651-64 [DOI] 10.1089/ars.2014.6074. [PMID] 25891177.
2015
Correction: Chapman, E.; et al. Inhibitors of the AAA+ chaperone p97. Molecules 2015, 20, 3027-3049.
Molecules (Basel, Switzerland). 20(3):4357-8 [DOI] 10.3390/molecules20034357. [PMID] 25759952.
2015
Functional chromatographic technique for natural product isolation.
Organic & biomolecular chemistry. 13(8):2255-9 [DOI] 10.1039/c4ob02292k. [PMID] 25588099.
2015
Inhibitors of the AAA+ chaperone p97.
Molecules (Basel, Switzerland). 20(2):3027-49 [DOI] 10.3390/molecules20023027. [PMID] 25685910.
2015
Molecular mechanisms of Nrf2 regulation and how these influence chemical modulation for disease intervention.
Biochemical Society transactions. 43(4):680-6 [DOI] 10.1042/BST20150020. [PMID] 26551712.
2015
p62 links autophagy and Nrf2 signaling.
Free radical biology & medicine. 88(Pt B):199-204 [DOI] 10.1016/j.freeradbiomed.2015.06.014. [PMID] 26117325.
2015
The Hybrid Pyrroloisoindolone-Dehydropyrrolizine Alkaloid (-)-Chlorizidine A Targets Proteins within the Glycolytic Pathway.
Chembiochem : a European journal of chemical biology. 16(14):2002-6 [DOI] 10.1002/cbic.201500229. [PMID] 26267855.
2015
Unfolded DapA forms aggregates when diluted into free solution, confounding comparison with folding by the GroEL/GroES chaperonin system.
FEBS letters. 589(4):497-499 [DOI] 10.1016/j.febslet.2015.01.008. [PMID] 25601566.
2015
Withaferin A Analogs That Target the AAA+ Chaperone p97.
ACS chemical biology. 10(8):1916-1924 [DOI] 10.1021/acschembio.5b00367. [PMID] 26006219.
2014
A biochemical screen for GroEL/GroES inhibitors.
Bioorganic & medicinal chemistry letters. 24(3):786-9 [DOI] 10.1016/j.bmcl.2013.12.100. [PMID] 24418775.
2014
Functional chromatography reveals three natural products that target the same protein with distinct mechanisms of action.
Chembiochem : a European journal of chemical biology. 15(14):2125-31 [DOI] 10.1002/cbic.201402258. [PMID] 25125376.
2014
Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis.
Genes & development. 28(7):708-22 [DOI] 10.1101/gad.238246.114. [PMID] 24636985.
2014
Oncogenic KRAS confers chemoresistance by upregulating NRF2.
Cancer research. 74(24):7430-41 [DOI] 10.1158/0008-5472.CAN-14-1439. [PMID] 25339352.
2013
USP15 negatively regulates Nrf2 through deubiquitination of Keap1.
Molecular cell. 51(1):68-79 [DOI] 10.1016/j.molcel.2013.04.022. [PMID] 23727018.
2008
Requirement for binding multiple ATPs to convert a GroEL ring to the folding-active state.
Proceedings of the National Academy of Sciences of the United States of America. 105(49):19205-10 [DOI] 10.1073/pnas.0810657105. [PMID] 19050077.
2002
A potent and highly selective sulfotransferase inhibitor.
Journal of the American Chemical Society. 124(49):14524-5 [PMID] 12465948.

Grants

May 2024 ACTIVE
Redox and Protein Homeostasis in Arsenic Tumorigenicity
Role: Principal Investigator
Funding: NATL INST OF HLTH NIEHS
Apr 2024 ACTIVE
NRF Transcription Factors in Environmental Stress and Disease Intervention
Role: Co-Investigator
Funding: NATL INST OF HLTH NIEHS

Education

PhD
2002 · The Scripps Research Institute
MA
1998 · Columbia University
BS
1996 · UC Berkeley

Contact Details

Phones:
Business:
(561) 228-2559
Emails:
Business:
chapmaneli@ufl.edu
Addresses:
Business Mailing:
130 SCRIPPS WAY
JUPITER FL 33458
Business Street:
120 SCRIPPS WAY
JUPITER FL 33458