About

Timothy Arthur James Haystead is a Professor of Pharmacology and Cancer Biology at Duke University. He is also an Associate Professor in Pathology and a member of the Duke Cancer Institute. His roles involve leading research in pharmacology and cancer biology, contributing to the academic and scientific community at Duke. His primary faculty position is based at the Duke University Medical Center in Durham, North Carolina, where he is engaged in advancing understanding in his fields of expertise.

Research topics

• Biology
• Cell biology
• Medicine
• Cancer research
• Internal medicine
• Immunology
• Genetics
• Oncology
• Biochemistry
• Chemistry

Selected publications

• Pharmacological inhibition of transforming growth factor-β activated kinase 1 (TAK1) prevents chemotherapy induced peripheral neuropathy (CIPN)

  Journal of Pain · 2026-03-31 · 1 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Mechanism of Impaired Protein Homeostasis in Kidney Grafts Following Cold Storage and Transplantation (Abstract ID: 162640)

  Journal of Pharmacology and Experimental Therapeutics · 2025-03-01

  article
  PublisherDOI

• An Inhibitor of Death-Associated Protein Kinase 3 (DAPK3) Disrupts Hippo Signaling and Intestinal Epithelial Regeneration in Murine DSS-Induced Colitis

  Digestive Diseases and Sciences · 2025-11-07

  articleOpen access
  PublisherOA PDFDOI

• Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome

  Cell chemical biology · 2024-03-15 · 17 citations

  articleOpen access
  PublisherOA PDFDOI

• TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers

  Cell Death and Disease · 2024-04-17 · 12 citations

  articleOpen access

  Poor survival and lack of treatment response in glioblastoma (GBM) is attributed to the persistence of glioma stem cells (GSCs). To identify novel therapeutic approaches, we performed CRISPR/Cas9 knockout screens and discovered TGFβ activated kinase (TAK1) as a selective survival factor in a significant fraction of GSCs. Loss of TAK1 kinase activity results in RIPK1-dependent apoptosis via Caspase-8/FADD complex activation, dependent on autocrine TNFα ligand production and constitutive TNFR signaling. We identify a transcriptional signature associated with immune activation and the mesenchymal GBM subtype to be a characteristic of cancer cells sensitive to TAK1 perturbation and employ this signature to accurately predict sensitivity to the TAK1 kinase inhibitor HS-276. In addition, exposure to pro-inflammatory cytokines IFNγ and TNFα can sensitize resistant GSCs to TAK1 inhibition. Our findings reveal dependency on TAK1 kinase activity as a novel vulnerability in immune-activated cancers, including mesenchymal GBMs that can be exploited therapeutically.

  PublisherOA PDFDOI

• Cooperative involvement of zipper-interacting protein kinase (ZIPK) and the dual-specificity cell-division cycle 14A phosphatase (CDC14A) in vascular smooth muscle cell migration

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-09

  preprintOpen access

  Zipper-interacting protein kinase (ZIPK) is a Ser/Thr protein kinase with regulatory involvement in vascular smooth muscle cell (VSMC) actin polymerization and focal adhesion assembly dynamics. ZIPK silencing can induce cytoskeletal remodeling with disassembly of actin stress fiber networks and coincident loss of focal adhesion kinase (FAK)-pY397 phosphorylation. The link between ZIPK inhibition and FAK phosphorylation is unknown, and critical interactor(s) and regulator(s) are not yet defined. In this study, we further analyzed the ZIPK-FAK relationship in VSMCs. The application of HS38, a selective ZIPK inhibitor, to coronary artery vascular smooth muscle cells (CASMCs) suppressed cell migration, myosin light chain phosphorylation (pT18&pS19) and FAK-pY397 phosphorylation as well. This was associated with the translocation of cytoplasmic FAK to the nucleus. ZIPK inhibition with HS38 was consistently found to suppress the activation of FAK and attenuate the phosphorylation of other focal adhesion protein components (i.e., pCas130, paxillin, ERK). In addition, our study showed a decrease in human cell-division cycle 14A phosphatase (CDC14A) levels with ZIPK-siRNA treatment and increased CDC14A with transient transfection of ZIPK. Proximity ligation assays (PLA) revealed CDC14A localized with ZIPK and FAK. Silencing CDC14A showed an increase of FAK-pY397 phosphorylation. Ultimately, the data presented herein strongly support a regulatory mechanism of FAK in CASMCs by a ZIPK-CDC14A partnership; ZIPK may act as a key signal integrator to control CDC14A and FAK during VSMC migration.

  PublisherOA PDFDOI

• Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models

  Journal of Pain Research · 2024-06-01 · 3 citations

  articleOpen access

  Purpose: Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA) and gout, persistent inflammation due to long-term overexpression of several key cytokines has been linked to neuronal hypersensitivity and damage within the joints. Ultimately, a subset of patients develop chronic pain. Pharmacologic treatment of joint pain involves the use of analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, as well as intra-articular injections of corticosteroids and hyaluronic acid. However, NSAIDs are short-acting and fail to alleviate severe pain, opioids are generally ineffective at managing chronic pain, and all therapeutic options involve increased risks of serious side effects. Methods: We explored the therapeutic and analgesic effects of transforming growth factor-β-activated kinase 1 (TAK1) inhibition in both the monoiodoacetate (MIA) and monosodium urate (MSU) models of joint pain as an innovative strategy for alleviating chronic inflammatory pain. Mechanical allodynia (Von Frey), weight-bearing and histological changes were measured in separate groups of rats receiving either the selective TAK1 inhibitor, HS-276, gabapentin or vehicle. Results: Our data support that TAK1 inhibition effectively prevented the development of mechanical allodynia and differential weight-bearing in the MIA model. In the MSU model of gouty arthritis, treatment with HS-276 significantly reduced mechanical allodynia and knee edema in female rats, but not male rats. Histological evaluation of effected joints in both models showed that HS-276 treatment significantly reduced disease-induced degradation of the joint. Conclusion: Our results support that TAK1 is a critical signaling node in inflammatory joint diseases such as OA and gouty arthritis. Selective pharmacological inhibition significantly attenuated several aspects of the disease, including joint degeneration and mechanical pain. Thus, TAK1 is a novel therapeutic target for the treatment of painful inflammatory joint diseases. Perspective: This article reports on the therapeutic potential of TAK1 in the treatment of chronic inflammatory joint diseases such as OA and gout. Using the selective TAK1 inhibitor, HS-276, we show the therapeutic and analgesic effects of TAK1 inhibition in two preclinical murine models of inflammatory joint pain.

  PublisherOA PDFDOI

• Death‐associated protein kinase 3 regulates the myogenic reactivity of cerebral arteries

  Experimental Physiology · 2023-04-21 · 8 citations

  articleOpen access

  NEW FINDINGS: -sensitization of vascular smooth muscle contraction: does this protein kinase participate in the myogenic response of cerebral arteries? What is the main finding and its importance? Small molecule inhibitors of DAPK3 effectively block the myogenic responses of cerebral arteries. HS38-dependent changes to vessel constriction occur independent of LC20 phosphorylation, and therefore DAPK3 appears to operate via the actin cytoskeleton. A role for DAPK3 in the myogenic response was not previously reported, and the results support a potential new therapeutic target in the cerebrovascular system. ABSTRACT: sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. A slow return of myogenic tone was observed during the sustained ex vivo exposure of cerebral arteries to HS38. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signalling compensation in response to attenuation of DAPK3 activity. Additional experiments with VSM cells revealed HS38- and siDAPK-dependent effects on the actin cytoskeleton and focal adhesion kinase phosphorylation status. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38-dependent attenuation of myogenic reactivity found for human pial vessels.

  PublisherOA PDFDOI

• Supplementary Figure Legends from <i>In Vivo</i> Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior

  2023-03-31

  preprintOpen access

  <p>Figure Legends for Supplementary Figures 1-4</p>

  PublisherDOI

• Supplementary Figure 4 from <i>In Vivo</i> Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior

  2023-03-31

  preprintOpen access

  <p>HSP90 surface expression on Breast Cancer Cell Lines</p>

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AI08952604

  NIH · $764k · 2015

• NIH Grant P01HL019242

  NIH · $25.4M · 2010

• NIH Grant R01DK052378

  NIH · $2.1M · 2006

• NIH Grant R01AI089526

  NIH · $3.4M · 2016

• NIH Grant R01DK065954

  NIH · $1.2M · 2010

Frequent coauthors

• Philip F. Hughes

  Duke University

  95 shared

• Justin A. MacDonald

  University of Calgary

  84 shared

• Christopher N. Fortner

  SUNY Upstate Medical University

  59 shared

• David R. Loiselle

  Duke University

  58 shared

• Thomas M. Coffman

  Duke-NUS Medical School

  55 shared

• Susan B. Gurley

  University of Southern California

  54 shared

• Matthew A. Sparks

  Georgetown University

  53 shared

• Thu H. Le

  University of Rochester Medical Center

  50 shared