Haystead Lab Pioneering Precision Agents for Chaperone Protien Expressive Diseases

Research

The landscape of radiotherapeutic and molecular imaging strategies is rapidly evolving, yet translating biological insight into precise diagnostic and therapeutic tools remains complex. Our laboratory develops small-molecule probes and radiolabeled platforms that integrate chemical biology, quantitative imaging, positron emission tomography, and computational modeling to better understand and treat disease. We design approaches that are mechanistically rigorous, broadly applicable, and grounded in reproducible science to advance impactful translational research.

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All

2025

An Inhibitor of Death-Associated Protein Kinase 3 DAPK3 Disrupts Hippo Signaling and Intestinal Epithelial Regeneration in Murine DSS-Induced Colitis
An Inhibitor of Death-Associated Protein Kinase 3 (DAPK3) Disrupts Hippo Signaling and Intestinal Epithelial Regeneration in Murine DSS-Induced Colitis
Huey-Miin Chen, David A. Carlson, Timothy A. J. Haystead, Justin A. MacDonald
Digestive Diseases and Sciences  ·  07 Nov 2025  ·  doi:10.1007/s10620-025-09505-x

2024

Transforming Growth Factor-β-Activated Kinase 1 TAK1 Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models
Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models
Robert Freeze, Philip Hughes, Timothy Haystead, Scott Scarneo
Journal of Pain Research  ·  01 Jun 2024  ·  doi:10.2147/JPR.S451409
TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers
TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers
Helene Damhofer, Tülin Tatar, Benjamin Southgate, Scott Scarneo, Karl Agger, …, Gillian M. Morrison, Philip F. Hughes, Timothy Haystead, Steven M. Pollard, Kristian Helin
Cell Death & Disease  ·  17 Apr 2024  ·  doi:10.1038/s41419-024-06654-1
Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome
Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome
Christopher R. Mansfield, Baiyi Quan, Michael E. Chirgwin, Benjamin Eduful, Philip F. Hughes, …, Björn F.C. Kafsack, Timothy A.J. Haystead, James W. Leahy, Michael C. Fitzgerald, Emily R. Derbyshire
Cell Chemical Biology  ·  01 Apr 2024  ·  doi:10.1016/j.chembiol.2024.02.008
Cooperative involvement of zipper-interacting protein kinase ZIPK and the dual-specificity cell-division cycle 14A phosphatase CDC14A in vascular smooth muscle cell migration
Cooperative involvement of zipper-interacting protein kinase (ZIPK) and the dual-specificity cell-division cycle 14A phosphatase (CDC14A) in vascular smooth muscle cell migration
Abdulhameed Al-Ghabkari, David A. Carlson, Timothy A. J. Haystead, Justin A. MacDonald
openRxiv  ·  09 Mar 2024  ·  doi:10.1101/2024.03.06.583600
Targeting Borrelia burgdorferi HtpG with a berserker molecule, a strategy for anti-microbial development
Targeting Borrelia burgdorferi HtpG with a berserker molecule, a strategy for anti-microbial development
Dave L. Carlson, Mark Kowalewski, Khaldon Bodoor, Adam D. Lietzan, Philip F. Hughes, …, Jennifer C. Miller, Christine Jacobs-Wagner, Matthew R. Redinbo, Neil Spector, Timothy A.J. Haystead
Cell Chemical Biology  ·  01 Mar 2024  ·  doi:10.1016/j.chembiol.2023.10.004

2023

Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein
Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein
Timothy Haystead, Eric Lee, Kirstin Cho, Gail Gullickson, Philip Hughes, Greta Krafsur, Robert Freeze, Scott Scarneo
Scientific Reports  ·  18 Dec 2023  ·  doi:10.1038/s41598-023-49077-2
Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis
Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis
Swarna Bale, Priyanka Verma, Bharath Yalavarthi, Scott Arthur Scarneo, Philip Hughes, …, Pei-Suen Tsou, Dinesh Khanna, Timothy A.J. Haystead, Swati Bhattacharyya, John Varga
JCI Insight  ·  24 Jul 2023  ·  doi:10.1172/jci.insight.165358

2022

Expression of membrane Hsp90 is a molecular signature of T cell activation
Expression of membrane Hsp90 is a molecular signature of T cell activation
Scott A. Scarneo, Aaron P. Smith, Jacob Favret, Robert O’Connell, Joy Pickeral, …, Bryan Scott, Debashish Roy, Barton F. Haynes, Jesse J. Kwiek, Timothy A. J. Haystead
Scientific Reports  ·  27 Oct 2022  ·  doi:10.1038/s41598-022-22788-8
Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatment of Inflammatory Arthritis
Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatment of Inflammatory Arthritis
Scott Scarneo, Philip Hughes, Robert Freeze, Kelly Yang, Juliane Totzke, Timothy Haystead
ACS Chemical Biology  ·  02 Mar 2022  ·  doi:10.1021/acschembio.1c00788

2021

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
Ria Goswami, Veronica S. Russell, Joshua J. Tu, Charlene Thomas, Philip Hughes, …, Justin Steppe, Scott M. Palmer, Timothy Haystead, Maria Blasi, Sallie R. Permar
iScience  ·  01 Dec 2021  ·  doi:10.1016/j.isci.2021.103412
Expression of ectopic heat shock protein 90 in male and female primary afferent nociceptors regulates inflammatory pain
Expression of ectopic heat shock protein 90 in male and female primary afferent nociceptors regulates inflammatory pain
Yaomin Wang, Scott A. Scarneo, Shin Hyung Kim, Xin Zhang, Jiegen Chen, Kelly W. Yang, Philip Hughes, Timothy Haystead, Andrea G. Nackley
Pain  ·  12 Oct 2021  ·  doi:10.1097/j.pain.0000000000002511
Understanding the sources of errors in ex vivo Hsp90 molecular imaging for rapid-on-site breast cancer diagnosis
Understanding the sources of errors in ex vivo Hsp90 molecular imaging for rapid-on-site breast cancer diagnosis
Roujia Wang, Daniel A. Alvarez, Brian T. Crouch, Aditi Pilani, Christopher Lam, Caigang Zhu, Philip Hughes, David Katz, Timothy Haystead, Nirmala Ramanujam
Biomedical Optics Express  ·  23 Mar 2021  ·  doi:10.1364/BOE.418818

2020

TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases
TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases
Juliane Totzke, Scott A. Scarneo, Kelly W. Yang, Timothy A. J. Haystead
Open Biology  ·  01 Sep 2020  ·  doi:10.1098/rsob.200099
Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors
Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors
Kensuke Kaneko, Takuya Osada, Michael A. Morse, William R. Gwin, Joshua D. Ginzel, …, Márcio A. Diniz, Khaldon Bodoor, Philip F. Hughes, Timothy AJ. Haystead, H. Kim Lyerly
Communications Biology  ·  08 May 2020  ·  doi:10.1038/s42003-020-0956-7
A highly selective inhibitor of interleukin-1 receptor associated kinases 1 4 IRAK-1 4 delineates the distinct signaling roles of IRAK-1 4 and the TAK1 kinase
A highly selective inhibitor of interleukin-1 receptor–associated kinases 1/4 (IRAK-1/4) delineates the distinct signaling roles of IRAK-1/4 and the TAK1 kinase
Scott A. Scarneo, Philip F. Hughes, Kelly W. Yang, David A. Carlson, Deepak Gurbani, Kenneth D. Westover, Timothy A.J. Haystead
Journal of Biological Chemistry  ·  01 Feb 2020  ·  doi:10.1074/jbc.RA119.011857

2019

Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice
Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice
Scott A. Scarneo, Liesl S. Eibschutz, Phillip J. Bendele, Kelly W. Yang, Juliane Totzke, Philip Hughes, David A. Fox, Timothy A. J. Haystead
Arthritis Research & Therapy  ·  01 Dec 2019  ·  doi:10.1186/s13075-019-2073-x
Exploiting heat shock protein expression to develop a non-invasive diagnostic tool for breast cancer
Exploiting heat shock protein expression to develop a non-invasive diagnostic tool for breast cancer
Brian T. Crouch, Jennifer Gallagher, Roujia Wang, Joy Duer, Allison Hall, Mary Scott Soo, Philip Hughes, Timothy Haystead, Nirmala Ramanujam
Scientific Reports  ·  05 Mar 2019  ·  doi:10.1038/s41598-019-40252-y

2018

Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development
Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development
Len Neckers, Brian Blagg, Timothy Haystead, Jane B. Trepel, Luke Whitesell, Didier Picard
Cell Stress and Chaperones  ·  01 Jul 2018  ·  doi:10.1007/s12192-018-0877-2
Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity
Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity
Dora Posfai, Amber L. Eubanks, Allison I. Keim, Kuan-Yi Lu, Grace Z. Wang, Philip F. Hughes, Nobutaka Kato, Timothy A. Haystead, Emily R. Derbyshire
Antimicrobial Agents and Chemotherapy  ·  01 Apr 2018  ·  doi:10.1128/AAC.01799-17

2017

i In Vivo i Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior
In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior
Takuya Osada, Kensuke Kaneko, William R. Gwin, Michael A. Morse, Amy Hobeika, Brian W. Pogue, Zachary C. Hartman, Philip F. Hughes, Timothy Haystead, H. Kim Lyerly
Clinical Cancer Research  ·  14 Dec 2017  ·  doi:10.1158/1078-0432.CCR-17-1453
Fluorescent-Linked Enzyme Chemoproteomic Strategy FLECS for Identifying HSP70 Inhibitors
Fluorescent-Linked Enzyme Chemoproteomic Strategy (FLECS) for Identifying HSP70 Inhibitors
T. A. J. Haystead
Methods in Molecular Biology  ·  26 Nov 2017  ·  doi:10.1007/978-1-4939-7477-1_6
Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer
Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer
Caigang Zhu, Amy F. Martinez, Hannah L. Martin, Martin Li, Brian T. Crouch, David A. Carlson, Timothy A. J. Haystead, Nimmi Ramanujam
Scientific Reports  ·  23 Oct 2017  ·  doi:10.1038/s41598-017-14226-x
Cellular fatty acid synthase is required for late stages of HIV-1 replication
Cellular fatty acid synthase is required for late stages of HIV-1 replication
Manjusha M. Kulkarni, Annette N. Ratcliff, Menakshi Bhat, Yazan Alwarawrah, Philip Hughes, …, David Loiselle, Jordi B. Torrelles, Nicholas T. Funderburg, Timothy A. Haystead, Jesse J. Kwiek
Retrovirology  ·  29 Sep 2017  ·  doi:10.1186/s12977-017-0368-z
A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy i in Vivo i
A Fluorescent Hsp90 Probe Demonstrates the Unique Association between Extracellular Hsp90 and Malignancy in Vivo
Lauren B. Crowe, Philip F. Hughes, David A. Alcorta, Takuya Osada, Aaron P. Smith, …, Jose Roques, David Darr, H. Kim Lyerly, Neil L. Spector, Timothy A.J. Haystead
ACS Chemical Biology  ·  23 Feb 2017  ·  doi:10.1021/acschembio.7b00006

2016

An inducible heat shock protein 70 small molecule inhibitor demonstrates anti-dengue virus activity, validating Hsp70 as a host antiviral target
An inducible heat shock protein 70 small molecule inhibitor demonstrates anti-dengue virus activity, validating Hsp70 as a host antiviral target
Matthew K. Howe, Brittany L. Speer, Philip F. Hughes, David R. Loiselle, Subhash Vasudevan, Timothy A.J. Haystead
Antiviral Research  ·  01 Jun 2016  ·  doi:10.1016/j.antiviral.2016.03.017
Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2 Breast Cancer
Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2 + Breast Cancer
Yazan Alwarawrah, Philip Hughes, David Loiselle, David A. Carlson, David B. Darr, …, J. Will Thompson, Manjusha M. Kulkarni, Annette N. Ratcliff, Jesse J. Kwiek, Timothy A.J. Haystead
Cell Chemical Biology  ·  01 Jun 2016  ·  doi:10.1016/j.chembiol.2016.04.011

2015

Pregnancy and Smoothelin-like Protein 1 SMTNL1 Deletion Promote the Switching of Skeletal Muscle to a Glycolytic Phenotype in Human and Mice
Pregnancy and Smoothelin-like Protein 1 (SMTNL1) Deletion Promote the Switching of Skeletal Muscle to a Glycolytic Phenotype in Human and Mice
Beata Lontay, Khaldon Bodoor, Adrienn Sipos, Douglas H. Weitzel, David Loiselle, …, James Devente, Robert C. Hickner, Donald P. McDonnell, Thomas Ribar, Timothy A. Haystead
Journal of Biological Chemistry  ·  01 Jul 2015  ·  doi:10.1074/jbc.M115.658120

2014

Identification of an Allosteric Small-Molecule Inhibitor Selective for the Inducible Form of Heat Shock Protein 70
Identification of an Allosteric Small-Molecule Inhibitor Selective for the Inducible Form of Heat Shock Protein 70
Matthew K. Howe, Khaldon Bodoor, David A. Carlson, Philip F. Hughes, Yazan Alwarawrah, …, Theodore A. Gobillot, Dennis J. Thiele, Jeffrey L. Brodsky, Neil L. Spector, Timothy A.J. Haystead
Chemistry & Biology  ·  01 Dec 2014  ·  doi:10.1016/j.chembiol.2014.10.016

2013

Fluorescence Linked Enzyme Chemoproteomic Strategy for Discovery of a Potent and Selective DAPK1 and ZIPK Inhibitor
Fluorescence Linked Enzyme Chemoproteomic Strategy for Discovery of a Potent and Selective DAPK1 and ZIPK Inhibitor
David A. Carlson, Aaron S. Franke, Douglas H. Weitzel, Brittany L. Speer, Philip F. Hughes, …, Cindy Sutherland, Jing Ti Deng, Michael P. Walsh, Justin A. MacDonald, Timothy A. J. Haystead
ACS Chemical Biology  ·  17 Oct 2013  ·  doi:10.1021/cb400407c
Optical and Radioiodinated Tethered Hsp90 Inhibitors Reveal Selective Internalization of Ectopic Hsp90 in Malignant Breast Tumor Cells
Optical and Radioiodinated Tethered Hsp90 Inhibitors Reveal Selective Internalization of Ectopic Hsp90 in Malignant Breast Tumor Cells
Jared J. Barrott, Philip F. Hughes, Takuya Osada, Xiao-Yi Yang, Zachary C. Hartman, …, Nimmi Ramanujam, Ganesan Vaidyanathan, Michael R. Zalutsky, H. Kim Lyerly, Timothy A. Haystead
Chemistry & Biology  ·  01 Sep 2013  ·  doi:10.1016/j.chembiol.2013.08.004
Hsp90, an unlikely ally in the war on cancer
Hsp90, an unlikely ally in the war on cancer
Jared J. Barrott, Timothy A. J. Haystead
The FEBS Journal  ·  24 Feb 2013  ·  doi:10.1111/febs.12147

2012

A highly selective Hsp90 affinity chromatography resin with a cleavable linker
A highly selective Hsp90 affinity chromatography resin with a cleavable linker
Philip F. Hughes, Jared J. Barrott, David A. Carlson, David R. Loiselle, Brittany L. Speer, Khaldon Bodoor, Lauretta A. Rund, Timothy A.J. Haystead
Bioorganic & Medicinal Chemistry  ·  01 May 2012  ·  doi:10.1016/j.bmc.2012.03.043
Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer
Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer
Qing Cheng, Jeffrey T Chang, Joseph Geradts, Leonard M Neckers, Timothy Haystead, Neil L Spector, H Kim Lyerly
Breast Cancer Research  ·  17 Apr 2012  ·  doi:10.1186/bcr3168

2011

Smoothelin-like 1 Protein Is a Bifunctional Regulator of the Progesterone Receptor during Pregnancy
Smoothelin-like 1 Protein Is a Bifunctional Regulator of the Progesterone Receptor during Pregnancy
Khaldon Bodoor, Beata Lontay, Rachid Safi, Douglas H. Weitzel, David Loiselle, Zhengzheng Wei, Szabolcs Lengyel, Donald P. McDonnell, Timothy A. Haystead
Journal of Biological Chemistry  ·  01 Sep 2011  ·  doi:10.1074/jbc.M111.270397
Phosphorylation-dependent control of ZIPK nuclear import is species specific
Phosphorylation-dependent control of ZIPK nuclear import is species specific
Douglas H. Weitzel, Jenica Chambers, Timothy A.J. Haystead
Cellular Signalling  ·  01 Jan 2011  ·  doi:10.1016/j.cellsig.2010.09.016

2010

Smoothelin-like 1 Protein Regulates Myosin Phosphatase-targeting Subunit 1 Expression during Sexual Development and Pregnancy
Smoothelin-like 1 Protein Regulates Myosin Phosphatase-targeting Subunit 1 Expression during Sexual Development and Pregnancy*
Beata Lontay, Khaldon Bodoor, Douglas H. Weitzel, David Loiselle, Christopher Fortner, Szabolcs Lengyel, Donghai Zheng, James Devente, Robert Hickner, TimothyA.J. Haystead
Journal of Biological Chemistry  ·  01 Sep 2010  ·  doi:10.1074/jbc.M110.143966
Application of Chemoproteomics to Drug Discovery: Identification of a Clinical Candidate Targeting Hsp90
Application of Chemoproteomics to Drug Discovery: Identification of a Clinical Candidate Targeting Hsp90
Patrick Fadden, Kenneth H. Huang, James M. Veal, Paul M. Steed, Amy F. Barabasz, …, James Otto, Gijsbertus J. Pronk, Katleen Verleysen, Timothy A. Haystead, Steven E. Hall
Chemistry & Biology  ·  01 Jul 2010  ·  doi:10.1016/j.chembiol.2010.04.015

2008

Deletion of the Protein Kinase A Protein Kinase G Target SMTNL1 Promotes an Exercise-adapted Phenotype in Vascular Smooth Muscle
Deletion of the Protein Kinase A/Protein Kinase G Target SMTNL1 Promotes an Exercise-adapted Phenotype in Vascular Smooth Muscle
Anne A. Wooldridge, Christopher N. Fortner, Beata Lontay, Takayuki Akimoto, Ronald L. Neppl, …, Robert C. Hickner, Thomas M. Coffman, Avril V. Somlyo, Zhen Yan, Timothy A.J. Haystead
Journal of Biological Chemistry  ·  01 Apr 2008  ·  doi:10.1074/jbc.M708628200
Murine CD7 Shares Antigenic Cross-Reactivity with HSP-60
Murine CD7 Shares Antigenic Cross-Reactivity with HSP-60
Brandon A. Howard, Gregory D. Sempowski, Richard M. Scearce, Hua-Xin Liao, David M. Lee, Gordon K. Lam, Haiyen Chen, Patrick Fadden, Timothy Haystead, Barton F. Haynes
Hybridoma  ·  01 Apr 2008  ·  doi:10.1089/hyb.2007.0553