About

Jefferson Chan is an Associate Professor of Chemistry and the Principal Investigator at the Chan Lab. He completed his postdoctoral research at UC Berkeley and earned his PhD in Chemistry from Simon Fraser University (SFU). His professional contact is jeffchan at illinois.edu. The page lists him as the lead faculty member of the research group but does not provide further details about his specific research focus, background, or key contributions.

Research topics

• Chemistry
• Biology
• Optics
• Biochemistry
• Internal medicine
• Cancer research
• Nanotechnology
• Pathology
• Medicine
• Chromatography
• Organic chemistry

Selected publications

• Activatable Porphyrin-Based Sensors, Photosensitizers and Combination Therapeutics

  JACS Au · 2025-01-15 · 21 citations

  reviewOpen accessSenior authorCorresponding

  Porphyrins, known as the "pigments of life", have evolved from their natural roles into versatile tools for biomedical applications. The development of activatable porphyrins has significantly expanded their utility, enabling precise responses to a carefully selected target analyte. These advances have broadened their use in imaging, diagnosis, and therapy. These capabilities are driven by activity-based sensing (ABS), which enhances the selectivity and sensitivity to various disease biomarkers. However, their design and implementation are intrinsically complex. This perspective provides an easy-to-follow roadmap that details how such molecules can be developed. Furthermore, we highlight recent progress in ABS-modified porphyrins, focusing on how specific modifications achieve these remarkable properties across various biomedical platforms. The ongoing evolution of activatable porphyrins holds great promise for the development of sophisticated, responsive systems, offering more effective diagnostic and therapeutic tools.

  PublisherDOI

• Author response for "Logic-gated approach for targeted delivery and site-selective activation of photothermal agents in precision cancer treatment"

  2025-01-22

  peer-reviewSenior author
  PublisherDOI

• Logic-gated approach for targeted delivery and site-selective activation of photothermal agents in precision cancer treatment

  Chemical Science · 2025-01-01 · 5 citations

  articleOpen accessSenior authorCorresponding

  Logic-gated strategies represent a promising approach to achieving highly selective cancer therapies. In this work, we present LG-AB (Logic-Gated Aza-BODIPY), an OFF-ON photothermal therapy (PTT) agent designed to selectively target cancer cells. LG-AB undergoes a red-shift in its maximum absorbance wavelength when activated in the tumor microenvironment, enabling the molecule to precisely generate heat in the cancerous tissue upon light irradiation. Unlike conventional activatable agents that rely on a single biomarker, LG-AB employs an AND logic-gated design, where glucose transporter 1 (GLUT1) overexpression facilitates targeted cellular uptake in cancer cells, followed by activation through elevated glutathione (GSH) levels. Beyond demonstrating photothermal efficacy in human lung cancer and murine breast cancer cells, we show that LG-AB effectively attenuates cancer progression through heat-induced apoptosis, with minimal off-target effects to surrounding tissues. The versatility of this strategy is further demonstrated through the development and application of LG-CPT (Logic-Gated Camptothecin), which utilizes the same logic-gated design. Our results show that enhancing specificity and limiting collateral damage can be broadly applied across different therapeutic agents.

  PublisherOA PDFDOI

• Donor-PeT Control of Intersystem Crossing Enables ALDH1A1-Activated Photodynamic Therapy

  ACS Chemical Biology · 2025-12-16 · 1 citations

  articleOpen accessSenior authorCorresponding

  Aldehyde dehydrogenase 1A1 (ALDH1A1) is highly expressed in therapy-resistant and metastatic cancers and represents a clinically relevant biomarker for selective activation strategies. We report AAP, an OFF-ON photosensitizer activated through ALDH1A1-mediated oxidation that produces singlet oxygen upon light exposure. AAP uses a donor photoinduced electron transfer (d-PeT) mechanism to suppress intersystem crossing in its unreacted benzaldehyde form, which minimizes background activity. Oxidation by ALDH1A1 disrupts d-PeT and restores phototoxicity. AAP showed minimal off-target activation by other ALDH isoforms or oxidative stress. In vivo, AAP suppressed tumor growth in two non-small cell lung cancer (NSCLC) models. In the first, intratumoral delivery into established tumors confirmed efficacy and ALDH1A1 dependence. In the second, liposomal AAP enabled intravenous delivery to early stage lesions with limited vascularization where treatment remained effective. These findings establish d-PeT suppression of intersystem crossing as an effective chemical biology strategy for enzyme-activated photodynamic therapy.

  PublisherOA PDFDOI

• 384 | PROGNOSTIC AND FUNCTIONAL IMPACT OF EGF‐JAK/STAT PATHWAY MUTATIONS IN ANGIOIMMUNOBLASTIC T‐CELL LYMPHOMA

  Hematological Oncology · 2025-06-01

  articleOpen access

  J. Lim equally contributing author. Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) with limited therapeutic options and poor prognosis. While mutations in epigenetic regulators and T-cell receptor (TCR) signaling genes are well characterized, the role of the epidermal growth factor (EGF)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in AITL remains unclear. We investigated the prognostic and functional implications of EGF-JAK/STAT pathway mutations in AITL. Methods: Whole-exome sequencing and targeted deep sequencing were performed on two independent AITL cohorts: National Cancer Centre Singapore (NCCS, n = 137) and Atlas of Blood Cancer Genomes (ABCG, n = 118). Kaplan-Meier and Cox proportional hazard models were used to assess survival impact. Molecular dynamics (MD) simulations and immunohistochemistry (IHC) were conducted to characterize structural and expression changes in EGFR mutants. Functional validation was performed in 293T cells overexpressing wild-type and mutant EGFR (R803W, A864V). Western blot analysis was used to examine activation of downstream signaling pathways and response to EGFR inhibitors gefitinib and osimertinib. Results: EGF-JAK/STAT pathway mutations were identified in 20.3% (52/255) of AITL cases. EGFR was the only gene significantly associated with worse progression-free survival (PFS) in both NCCS and ABCG cohorts (p < 0.05). The recurrent EGFRR803W mutation was located in dominant tumor clones and was associated with elevated EGFR expression by IHC. MD simulations showed that R803W disrupted juxtamembrane (JM) interactions, leading to destabilization of the inactive conformation. In vitro, EGFRR803W and EGFRA864V enhanced phosphorylation of STAT5 compared to wild-type EGFR, supporting activation of the JAK/STAT pathway. Treatment with gefitinib and osimertinib inhibited STAT3 and extracellular signal-regulated kinase (ERK) phosphorylation, suggesting that EGFR mutations are targetable. Conclusions: EGFR mutations define a distinct subset of AITL with poor prognosis and aberrant activation of JAK/STAT signaling. Their presence in dominant tumor clones and their ability to activate oncogenic signaling suggest a driver role in AITL. The suppression of signaling by EGFR inhibitors supports the potential for targeted therapies in EGFR-mutant AITL. These findings highlight the importance of EGF-JAK/STAT pathway mutations as novel prognostic and therapeutic targets in AITL. Research funding declaration: The study was supported by grants from the NCCS Research Fund, Singapore Ministry of Health’s National Medical Research Council, Tanoto Foundation Professorship in Medical Oncology, New Century International Pte Ltd, and Ling Foundation. Keywords: genomics, epigenomics, and other -omics; aggressive T-cell non-Hodgkin lymphoma; diagnostic and prognostic biomarkers No potential sources of conflict of interest.

  PublisherOA PDFDOI

• 666 | OUTCOMES OF RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA IN AN ASIAN MULTIETHNIC COHORT

  Hematological Oncology · 2025-06-01

  articleOpen accessSenior author

  Background: Though the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured following first- line rituximab-based chemoimmunotherapy, approximately one-third of patients will experience refractory disease or relapse (R/R) after the initial response. Recently, several novel agents, such as bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy, have been approved for R/R DLBCL. However, the high costs of these new therapies present a challenge for widespread implementation, particularly across many Asian countries. Aims: We aim to characterise patients with R/R DLBCL treated at the National Cancer Centre Singapore and Singapore General Hospital to appraise the real-world clinical need to adopt new therapeutics in this disease entity. Methods: Overall survival (OS) and progression-free survival (PFS) estimates were compared using the Kaplan- Meier method and log-rank test. Results: 1071 patients diagnosed with DLBCL between 2010 and 2022 were retrospectively reviewed, with a final cohort of 227 patients included in the final analysis after excluding those treated with CAR-T therapy, incomplete data, and dual malignancy. 139 (61.2%) were male, and 152 (67.0%) were older than 60 years at the time of R/R disease. 150 (66.1%) patients were found to have relapsed within 1 year from completion of initial therapy, the majority of whom relapsed within 6 months (n = 104). In this group of patients, median PFS was 3.2 months compared to 15.3 months for those who relapsed beyond 1 year (HR 2.00, 95% CI: 1.49 to 2.68, p < 0.0001). Median OS was 8.6 months and 34.2 months, respectively (HR 1.73, 95% CI: 1.26 to 2.37, p = 0.0007). We focused on 123 patients identified using criteria defined by the SCHOLAR-1 study, including those refractory to first-line therapy (n = 57), refractory to second line- therapy and beyond (n = 57), and relapsing within 12 months after transplant (n = 9). From the time of diagnosis of R/R DLBCL, median OS for patients in the whole SCHOLAR-1 cohort who received further salvage therapy (90 of 123, 73.2%) was significantly improved over supportive care alone at 9.2 and 4.5 months, respectively (HR 2.33, 95% CI: 1.40 to 3.88, p = 0.0011). In terms of survival outcomes for patients who received further salvage therapy, median OS was only 7.4 months from the time of treatment initiation and was particularly dismal in the primary refractory group at 4.7 months, and in those refractory to second line-therapy and beyond at 8.7 months. Notably, for the majority of patients who did not achieve complete response to salvage therapy (84.8%), the median OS was only 5.3 months Summary/Conclusion: Our study builds on the evidence outlined by the SCHOLAR-1 study, which suggests that despite conventional treatment modalities, patients with R/R DLBCL have dismal outcomes. These data provide a real-world benchmark and justifies the compelling need for greater accessibility to novel therapies for R/R DLBCL. Encore Abstract: EHA 2025 Keywords: aggressive B-cell non-Hodgkin lymphoma No potential sources of conflict of interest.

  PublisherOA PDFDOI

• Activity-based sensing reveals elevated labile copper promotes liver aging via hepatic ALDH1A1 depletion

  Nature Communications · 2025-02-20 · 16 citations

  articleOpen accessSenior author

  Oxidative stress plays a key role in aging and related diseases, including neurodegeneration, cancer, and organ failure. Copper (Cu), a redox-active metal ion, generates reactive oxygen species (ROS), and its dysregulation contributes to aging. Here, we develop activity-based imaging probes for the sensitive detection of Cu(I) and show that labile hepatic Cu activity increases with age, paralleling a decline in ALDH1A1 activity, a protective hepatic enzyme. We also observe an age-related decrease in hepatic glutathione (GSH) activity through noninvasive photoacoustic imaging. Using these probes, we perform longitudinal studies in aged mice treated with ATN-224, a Cu chelator, and demonstrate that this treatment improves Cu homeostasis and preserves ALDH1A1 activity. Our findings uncover a direct link between Cu dysregulation and aging, providing insights into its role and offering a therapeutic strategy to mitigate its effects. Copper (Cu) dysregulation contributes to aging and oxidative stress. Here the authors develop imaging probes to detect labile hepatic Cu, revealing age-related increases that deplete ALDH1A1 activity, and show that chelation therapy restores Cu homeostasis, offering a potential strategy to mitigate liver aging.

  PublisherOA PDFDOI

• Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells

  Cancer Letters · 2025-10-29 · 4 citations

  articleOpen access
  PublisherOA PDFDOI

• Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-02 · 5 citations

  preprintOpen access

  Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME). Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast cancer cells, resulting in loss of adherence, increased migratory capacity and resistance to cytotoxic chemotherapy. Decreased microRNAs (miRs) within the sEVs resulted in activation of the WNT/β-catenin signaling pathway in recipient cells and suggest that this may be a predominant pathway for stem-like phenotype and EMT. Our findings underscore a novel mechanism by which 27HC-modulated neutrophils contribute to breast cancer pathophysiology through EV-mediated intercellular communication, suggesting potential therapeutic targets in cancer treatment.

  PublisherOA PDFDOI

• Structural and computational analysis of Y0.88Ni3-xMnx compounds to understand the localization of Mn atoms

  HAL (Le Centre pour la Communication Scientifique Directe) · 2024-07-02

  articleOpen access

  National audience

  PublisherOA PDF

Recent grants

• NIH Grant R56CA091907

  NIH · $331k · 2009

• NIH Grant R01NS065223

  NIH · $1.6M · 2015

• Molecular and metabolic pathology of CNC-bZIP knockouts

  NIH · $3.4M · 2003–2016

• NIH Grant K08DK002603

  NIH · $593k · 2003

• CAREER: Photoacoustic Imaging Probes to Study the Biology of Metal Ions

  NSF · $625k · 2018–2023

Frequent coauthors

• Christopher J. Chang

  Colorado State University

  24 shared

• Melissa Y. Lucero

  University of Illinois Urbana-Champaign

  21 shared

• Anuj K. Yadav

  21 shared

• Christopher J. Reinhardt

  Scripps Research Institute

  17 shared

• Sarah H. Gardner

  University of Illinois Urbana-Champaign

  13 shared

• Shengzhang Su

  University of Washington

  13 shared

• Andrew J. Bennet

  Simon Fraser University

  11 shared

• Amanda K. East

  University of Illinois Urbana-Champaign

  10 shared

Labs

• CHAN LABPI

Awards & honors

• Helen Corley Petit Scholar (2021)
• Teachers Ranked as Excellent (2021)
• Teachers Ranked as Excellent (2020)
• Beckman Fellow Award (2019)
• Thieme Chemistry Journal Award (2018)