About

Jack Elias is a Professor of Molecular Microbiology and Immunology at Brown University, holding the Warren Alpert Professorship in the Brown Institute for Translational Science. He is affiliated with the Division of Biology and Medicine at Brown University and is involved in research within the field of molecular microbiology and immunology. His work focuses on understanding the molecular mechanisms underlying microbial and immune system functions, contributing to advancements in translational science and medical research. As a faculty member, he is engaged in teaching, mentoring, and leading research initiatives aimed at elucidating complex biological processes related to microbiology and immunology.

Research topics

• Virology
• Medicine
• Internal medicine

Selected publications

• Bispecific targeting of CHI3L1 and PD-1 as a therapeutic strategy for pulmonary fibrosis

  JCI Insight · 2026-04-28

  articleOpen access

  CHI3L1, a chitinase-like protein, is implicated in pulmonary fibrosis, yet its mechanisms incompletely understood. In this study, we demonstrated that CHI3L1 coordinates profibrotic macrophage activation and invasive myofibroblast differentiation, and their crosstalk. In vitro, CHI3L1 drove M2-like macrophage polarization as evidenced by increased CD163, CD206, and PD-L1, and amplified TGF-β1-induced fibroblast responses, including myofibroblast transformation, migration, and invasion. Mechanistically, CHI3L1 enhanced TGF-β1 signaling through SMAD, AKT, and ERK pathways, and PD-L1 was required for CHI3L1/TGF-β1-driven myofibroblast transformation. Co-culture studies further demonstrated the ability of CHI3L1 to induce profibrotic macrophage activation that enhanced myofibroblast transformation mediated via a CD44-PD-L1 axis. In vivo, following bleomycin challenge, CHI3L1 transgenic mice exhibited increased PD-L1+ M2 macrophages, PD-L1+/PDGFRα+ fibroblasts, and PD-1+ immune cells compared with wild-type controls. Therapeutically, combined anti-CHI3L1 and anti-PD-1 antibodies, as well as a bispecific anti-CHI3L1-anti-PD-1 antibody, produced greater anti-fibrotic efficacy than monotherapy. These findings demonstrate crosstalk between CHI3L1 and the PD-1/PD-L1 pathway that promotes profibrotic macrophage activation and invasive fibroblast differentiation and support dual targeting of CHI3L1 and PD-1/PD-L1 as a promising therapeutic strategy for pulmonary fibrosis.

  PublisherDOI

• CHI3L1 Expression in Chordoma: Implications for Immunotherapeutic Intervention

  Preprints.org · 2026-01-30

  preprintOpen access

  Chordomas are rare, highly morbid tumors arising from notochordal progenitor cells along the spinal axis, associated with severe neurological complications and high recurrence rates. Their resistance to conventional therapies and limited options beyond surgical resection and high-dose radiation underscore the urgent need for novel therapeutic targets. Publicly available preliminary RNA sequencing data from the Chordoma Foundation identified chitinase-3-like 1 (CHI3L1), a secreted glycoprotein implicated in immune checkpoint regulation and epithelial-mesenchymal transition (EMT), as a promising candidate for chordoma immunotherapy. Yet, the comprehensive function of CHI3L1 in chordoma immune response remains unclear. To evaluate its presence in chordoma, we employed RNA-based analyses alongside enzyme-linked immunosorbent assays (ELISA) on commercially available chordoma cell lines (JHC7, U-CH12, U-CH1, U-CH1-N) and human chordoma tumor specimens. Our results demonstrate elevated CHI3L1 expression in chordoma cells relative to notochordal precursors, with comparative analyses revealing higher CHI3L1 expression in the primary tumor relative to recurrent samples. These findings suggest the potential role of CHI3L1 in chordoma tumorigenesis, emphasizing its relevance as a biomarker and therapeutic target for primary tumors. Future studies are necessary to elucidate the mechanistic role of CHI3L1 in chordoma immune evasion and to explore targeted interventions that may improve patient outcomes in this aggressive cancer.

  PublisherOA PDFDOI

• Deficiency of GCN5 exacerbates pulmonary fibrosis by disrupting the LKB1–AMPK pathway

  Cell Communication and Signaling · 2026-04-20

  articleOpen access
  PublisherDOI

• CHI3L1 Expression in Chordoma: Implications for Immunotherapeutic Intervention

  Cells · 2026-02-22

  articleOpen access

  Chordomas are rare, highly morbid tumors arising from notochordal progenitor cells along the spinal axis, associated with severe neurological complications and high recurrence rates. Their resistance to conventional therapies and limited options beyond surgical resection and high-dose radiation underscore the urgent need for novel therapeutic targets. Publicly available preliminary RNA sequencing data from the Chordoma Foundation identified chitinase-3-like 1 (CHI3L1), a secreted glycoprotein implicated in immune checkpoint regulation and epithelial-mesenchymal transition (EMT), as a promising candidate for chordoma immunotherapy. Yet, the comprehensive function of CHI3L1 in chordoma immune response remains unclear. To evaluate its presence in chordoma, we employed RNA-based analyses alongside enzyme-linked immunosorbent assays (ELISA) on commercially available chordoma cell lines (JHC7, U-CH12, U-CH1, U-CH1-N) and human chordoma tumor specimens. Our results demonstrate elevated CHI3L1 expression in chordoma cells relative to notochordal precursors, with comparative analyses revealing higher CHI3L1 expression in the primary tumor relative to recurrent samples. These findings suggest the potential role of CHI3L1 in chordoma tumorigenesis, emphasizing its relevance as a biomarker and therapeutic target for primary tumors. Future studies are necessary to elucidate the mechanistic role of CHI3L1 in chordoma immune evasion and to explore targeted interventions that may improve patient outcomes in this aggressive cancer.

  PublisherOA PDFDOI

• The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination

  JCI Insight · 2026-02-03

  articleOpen access

  Immunosuppression and metastasis are critical hallmarks of breast cancer, often linked to poor patient outcomes. The secreted cytokine chitinase-3-like 1 (CHI3L1) is frequently overexpressed in breast cancer samples and promotes an immunosuppressed tumor microenvironment. Notably, CHI3L1 expression is elevated in metastatic patient samples when compared with the matched primary breast tumor. To investigate its role in breast cancer metastasis, we generated an inducible genetically engineered mouse model that overexpresses CHI3L1 in the mammary epithelium. Ectopic expression of CHI3L1 in the polyomavirus middle T (PyMT) mouse model of breast cancer suppressed antitumor immune responses, accelerated mammary tumor onset, and enhanced lung metastasis. Mechanistically, elevated CHI3L1 expression in the mammary epithelium enhanced neutrophil recruitment, which subsequently degraded the extracellular matrix and increased the number of circulating tumor cells. These findings reveal a key mechanism driving metastatic dissemination and argue that therapeutically targeting Chi3l1 could enhance antitumor immunity and suppress metastasis.

  PublisherDOI

• Abstract 7024: Simultaneous targeting of CHI3L1 and PD-1/PD-L1 axis to overcome drug resistance and immune tolerance of EGFR non-small cell lung cancer.

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Background: Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer(NSCLC) accounts for 85% of all lung cancers. The overall prevalence rate of NSCLC with epidermalgrowth factor receptor (EGFR) mutations are significantly increasing in US. Oncogenic EGFR is atransmembrane protein which gets auto-phosphorylated to cause EGFR mutations (L858R, T790M, exon-19-deletion) in exon 18-21. Tyrosine kinase inhibitors (TKIs) are effectively targeted to treat mutated EGFRlung cancer. These TKIs showed favorable responses on patient’s treatments for 9-18 months but duringthe treatment, patients acquired EGFR mutations which results into the TKIs drug resistance and at thatpoint TKIs stops its efficacy for further treatment. Thus, there is a high medical unmet need for a newtherapeutic strategy to overcome drug resistance in patients with EGFR mutations. CHI3L1 expressed bymacrophages, neutrophils, epithelial cells, smooth muscle cells, chondrocytes including other immune cells.The levels of circulating CHI3L1 are increased in many malignancies including cancers of the prostate,colon, rectum, ovary, kidney, breast, glioblastomas, malignant melanoma, and lung cancer. CHI3L1contributes to pulmonary metastasis and spread via the regulation of immune-checkpoint (ICP) molecules.Our studies showed that CHI3L1 regulates and is a potent stimulator of PD-1/PD-L1 and PD-L2. CHI3L1stimulates the EGFR physiologic ligands EGF or TGF-a, a well-defined growth factors that stimulate EGFRphosphorylation. EGFR-YAP/TAZ signaling plays a growth-promoting role in cancers harboring EGFRalterations, and that inhibition of YAP/TAZ in combination with EGFR might be beneficial to prevent TKIdrug resistance and cancer recurrence. Methods: We analyzed EGFR mutant and resistant cells using techniques qPCR, protein accumulation,immuno-pull-down assay, immunofluorescence, FACS and therapeutic effect of YAP inhibitors in-vitroand in-vivo. Results: We identified that CHI3L1 augments YAP/TAZ nuclear translocation in EGFR mutant and TKIresistant cells. Also, YAP/TAZ inhibitors and agonists (Verteporfin, K-975) able to block YAP/TAZactivation and that suppress PD-1/PD-L1 in EGFR mutant and TKI resistant cells. Conclusion: These findings led us to understand that CHI3L1 and PD-1/PD-L1 axis mediated throughactivation of Hippo-YAP/TAZ signaling pathways play an essential role in TKIs drug resistance andimmune tolerance that enhances the progression of EGFR NSCLC. Additionally, simultaneous targeting ofCHI3L1 and PD-1/PD-L1 axis employing bispecific antibody (CHI3L1xPD-1) may provide a bettertherapeutic option to overcome TKI resistance and immune tolerance of EGFR NSCLC. Citation Format: Suchitra Kamle, Bing Ma, Brianna Pham, Isabella Fish, Marlo Hulnick, Taka Sadanaga, Hanseok Jeong, Mara Hofstetter, Hina Khan, Christopher Azzoli, Katerina A. Politi, Roy S. Herbst, Chun Geun Lee, Jack Elias. Simultaneous targeting of CHI3L1 and PD-1/PD-L1 axis to overcome drug resistance and immune tolerance of EGFR non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7024.

  PublisherDOI

• Chitinase 3-like-1 <i>(CHI3L1):</i> A potential prognostic biomarker for immunotherapy (IO) in non-small cell lung cancer (NSCLC).

  Journal of Clinical Oncology · 2025-05-28 · 3 citations

  articleSenior author

  e20622 Background: CHI3L1 is a member of the 18-glycosyl hydrolase gene family and is produced by a variety of cells including tumors and immune cells. It is overexpressed in several cancers and involved in cell death, innate immunity and tissue repair. Recent preclinical studies report that CHI3L1 regulates anti-tumor immune responses by inducing PD-1, PD-L1/2 and CTLA-4. Here we present the largest real-world dataset, investigating the association of tumor CHI3L1 RNA expression and clinical outcomes with immune checkpoint inhibitors in NSCLC. Methods: A total of 26,100 NSCLC specimens with paired DNA and RNA underwent gene expression profiling at Caris Life Sciences (Phoenix, AZ). Samples were stratified into quartiles based on CHI3L1 expression: top (Q4) and bottom (Q1). Tumors with known oncogenic drivers (DP) and lacking driver alterations (DN) were studied. PD-L1 expression was analyzed by IHC (22c3). Survival was calculated from claims data using Kaplan-Meier estimates as follows: survival on IO (IO-OS) from initiation of IO to last contact; and Pembrolizumab time on treatment (Pembro-ToT) from initiation to termination of Pembrolizumab. Hazard ratios (HR) and p-values were calculated using Cox proportional hazards model and log-rank test. Multiple hypothesis corrections were made where applicable (q &lt; 0.05). Results: Compared to Q1, patients with Q4 tumors had a higher median age (70 vs 68), more females (54 vs 44%), non-smokers (5 vs 3%) and predominantly adenocarcinoma (AD) histology (67 vs 54%), all q &lt; 0.05. Among drivers, KRAS (31 vs 25%) BRAF (5 vs 3%) and ALK alterations (6 vs 1%) were more prevalent in Q4 (all q &lt; 0.05). Mutations in RB1 (6 vs 11%) , KEAP1 (9 vs 18%), STK11 (9 vs 16%) and TP53 (62 vs 71%, all q &lt; 0.05) were less prevalent in Q4. In keeping with our report that CHI3L1 stimulates immune checkpoints, PD-L1+ (TPS &gt; 50%: 37 vs 22% and 1-49%: 32 vs 26%, both q &lt; 0.05) was more prevalent in Q4 and immune checkpoint expression ( CTLA4 , CD274 , HAVCR2 , IDO1 : 2.5-3.2 fold higher) and immune cell infiltrates (B-cells, neutrophils, M1 and M2 macrophages: 1.2-2 fold higher) were enriched in Q4 (all q &lt; 0.05). Importantly, the enhanced expression of CHI3L1 in Q4 patients was associated with favorable IO-OS and Pembro-ToT; across AD and squamous histology and across DP and DN tumors (Table). Conclusions: CHI3L1 is a compelling biomarker in NSCLC that associates enhanced expression of immune checkpoints and tumor and microenvironment inflammation. Notably, high CHI3L1 is also associated with longer IO-OS and Pembro-ToT, likely due to the effects of CHI3L1 on tumor and microenvironment inflammation. Further studies correlating CHI3L1 expression are warranted, to establish its utility as a biomarker for OS and IO response. Survival in Q4 vs. Q1- only statistically significant associations displayed. HR IO-OS Pembro-ToT AD 0.7 0.8 SQ 0.8 0.8 KRAS+ 0.6 0.8 Driver- 0.8 0.8

  PublisherDOI

• Switch-like methylation of functional pathways distinguishes COPD and idiopathic pulmonary fibrosis

  medRxiv · 2025-12-19

  preprintOpen access

  Abstract Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are phenotypically divergent disorders arising from similar exposures (including cigarette smoke). Differences in DNA methylation may drive the exposed lung towards COPD vs. IPF. To characterize differential methylation in COPD and IPF lung tissue relative to controls, we conducted epigenome-wide association studies of COPD and IPF in lung tissue from the Lung Tissue Research Consortium (N=1029), adjusting for age, sex, smoke exposure, ancestry, estimated cell type composition, and plate. “Switch probes” were defined as CpGs differentially methylated in COPD vs. control and IPF vs. control in opposite directions. Gaussian graphical models were used to mine network properties of switch probes. Differential methylation of genes related to COPD/IPF in the literature was assessed. Switch probe methylation was compared with previously reported gene expression to identify multi-omic switches. We found 13,313 CpGs were associated with COPD and 43,359 with IPF (3,163 overlapping). We identified 1,091 switch CpGs enriched for endocytosis, glycosphingolipid biosynthesis, and pathways in cancer. 24 genes exhibited multi-omic switch behavior, many related to lipid metabolism ( ACSL1 ; FASN ; LPCAT1 ; MED27 ; NCOR2 ). LPCAT1 is of particular interest due to its role in maintaining phosphatidylcholine, the majority component of surfactant. Further related to surfactant, we observed strong divergent methylation and expression of ATP11A , which facilitates endocytosis of surfactant lipids. CONCLUSIONS Our findings suggest multi-omic switch-like regulation may underlie differential COPD/IPF etiology. Future investigation of LPCAT1 and ATP11A could provide new mechanistic understanding and therapeutic avenues.

  PublisherOA PDFDOI

• Kasugamycin inhibits melanoma lung metastasis and regulates CHI3L1-driven M2-like tumor-associated macrophage differentiation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-28 · 1 citations

  preprintOpen access

  CHI3L1, a chitinase-like protein, is a potent immune modulator involved in various diseases, including lung cancer. While recent studies have demonstrated that kasugamycin (KSM) is a pan-chitinase inhibitor with strong anti-fibrotic activity, its effects on specific chitinase-like proteins remain undefined. This study shows that KSM effectively abrogates CHI3L1-stimulated cellular signaling and bioactivities. In a B16/F10 melanoma lung metastasis model, where CHI3L1 plays a critical role, KSM treatment significantly reduced melanoma lung metastasis dose-dependently. The anti-tumor effect of KSM was found to be CHI3L1-specific, as CHI3L1 overexpression enhanced melanoma lung colony formation, which was effectively blocked by KSM. In melanoma-challenged lungs, KSM treatment significantly reduced the elevation of M2 macrophages expressing CD206, CD163, and PD-L1. In studies using human monocytic THP-1 cells, CHI3L1 promoted M2 macrophage differentiation, which KSM significantly suppressed. Bulk RNA sequencing of differentiated macrophages revealed that CHI3L1 highly induced the expression of epidermal growth factor receptor (EGFR), and this induction was counter-regulated by KSM, and CHI3L1-driven M2 macrophage activation was reduced with EGFR blocker treatment. These findings reveal a novel anti-tumor mechanism of KSM, which inhibits M2-like tumor-associated macrophage differentiation, potentially through the CHI3L1-EGFR axis.

  PublisherOA PDFDOI

• Supplementary Table 1 from Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma

  2025-11-24

  articleOpen access

  &lt;p&gt;Supplementary Table 1&lt;/p&gt;

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL078744

  NIH · $2.0M · 2010

• NIH Grant R01HL054989

  NIH · $1.2M · 1999

• NIH Grant R01HL061904

  NIH · $1.5M · 2002

• NIH Grant R01HL079328

  NIH · $3.2M · 2013

• NIH Grant R01HL064242

  NIH · $3.1M · 2009

Frequent coauthors

• Chun Geun Lee

  525 shared

• Robert J. Homer

  170 shared

• Suchitra Kamle

  University of Rhode Island

  141 shared

• Chang-Min Lee

  Brown University

  103 shared

• Bing Ma

  98 shared

• Zhou Zhu

  Chinese Academy of Medical Sciences & Peking Union Medical College

  98 shared

• Bedia Akosman

  80 shared

• Yang Zhou

  Central South University

  73 shared

Education

• MD, Medical School

  University of Pennsylvania

  1976

• B.A., Biology

  University of Pennsylvania

  1973

Awards & honors

• Warren Alpert Professorship in the Brown Institute for Trans…