Kang Lab

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Rui Kang, M.D., Ph.D.

Dr. Kang's research is dedicated to elucidating the molecular and immunological roles of damage-associated molecular patterns (DAMPs) and pattern recognition receptors (PRRs) in inflammatory diseases. A central aspect of her research is the investigation of the receptor for advanced glycation end products (AGER, also known as RAGE), particularly focusing on its contributions to the pathogenesis and progression of severe infectious diseases and pancreatic cancer. Additionally, her research group is deeply engaged in uncovering the mechanisms underlying innate immunity responses during lethal infections, emphasizing translational relevance for improved therapeutic interventions.

Dr. Kang employs an extensive range of methodological approaches, leveraging transgenic and knockout mouse models to dissect the genetic and physiological aspects of inflammation and immunity. Her team also utilizes advanced human-derived organoid systems to closely mimic disease pathophysiology in vitro, along with various established and primary cell cultures to further explore cellular and molecular pathways. Analytical methods in her laboratory include the detailed assessment of inflammatory biomarkers, characterization of immune responses triggered by regulated cell death pathways, and comprehensive analysis of tumor microenvironment dynamics. Furthermore, her group routinely conducts rigorous evaluations of therapeutic efficacy, employing high-throughput drug screening and genome-wide studies to identify novel targets and molecular signatures critical for disease intervention and treatment.

Main Projects

1. The Role of AGER in Pancreatitis and Pancreatic Cancer 

AGER, a member of the immunoglobulin superfamily, functions as a key receptor for damage-associated molecular patterns (DAMPs) across a broad range of pathological conditions. It interacts with various ligands, including the chromatin-associated protein HMGB1. During my postdoctoral training in Dr. Herbert Zeh’s laboratory at the University of Pittsburgh, I developed the first AGER knockout (KO) mouse model on the KRAS-G12D-driven (KC) pancreatic cancer background, revealing AGER’s essential role in pancreatic tumorigenesis. Upon establishing my independent laboratory, we generated AGER flox/flox mice to investigate the tissue- and cell-type–specific roles of AGER in inflammation and cancer. Our studies have provided foundational insights into the role of AGER signaling in pancreatic cancer development and therapeutic response, particularly in relation to pancreatitis, autophagy, and regulated cell death pathways. Most recently, we demonstrated that AGER promotes resistance to KRAS-G12D inhibitors by enhancing macropinocytosis in pancreatic cancer cells.

Publications:

  • Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, Bierhaus A, Lotze MT, Zeh HJ. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010 Apr;17(4):666-76. doi: 10.1038/cdd.2009.149. Epub 2009 Oct 16. PubMed PMID: 19834494; PubMed Central PMCID: PMC3417122.
  • Kang R, Loux T, Tang D, Schapiro NE, Vernon P, Livesey KM, Krasinskas A, Lotze MT, Zeh HJ 3rd. The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia. Proc Natl Acad Sci U S A. 2012 May 1;109(18):7031-6. PubMed PMID: 22509024
  • Kang R, Hou W, Zhang Q, Chen R, Lee YJ, Bartlett DL, Lotze MT, Tang D, Zeh HJ. RAGE is essential for oncogenic KRAS-mediated hypoxic signaling in pancreatic cancer. Cell Death Dis. 2014 Oct 23;5(10):e1480. doi: 10.1038/cddis.2014.445. PMID: 25341034; PMCID: PMC4237264.
  • Kang R, Zhang Q, Hou W, Yan Z, Chen R, Bonaroti J, Bansal P, Billiar TR, Tsung A, Wang Q, Bartlett DL, Whitcomb DC, Chang EB, Zhu X, Wang H, Lu B, Tracey KJ, Cao L, Fan XG, Lotze MT, Zeh HJ 3rd, Tang D. Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice. Gastroenterology. 2014 Apr;146(4):1097-107. doi: 10.1053/j.gastro.2013.12.015. Epub 2013 Dec 17. PMID: 24361123; PMCID: PMC3965592.
  • Kang R, Chen R, Xie M, Cao L, Lotze MT, Tang D, Zeh HJ 3rd. The Receptor for Advanced Glycation End Products Activates the AIM2 Inflammasome in Acute Pancreatitis. J Immunol. 2016 May 15;196(10):4331-7. doi: 10.4049/jimmunol.1502340. Epub 2016 Apr 4. PMID: 27045109; PMCID: PMC4868774.
  • Yang L, Ye F, Liu J, Klionsky DJ, Tang D, Kang R. Extracellular SQSTM1 exacerbates acute pancreatitis by activating autophagy-dependent ferroptosis. Autophagy. 2023 Jun;19(6):1733-1744. doi: 10.1080/15548627.2022.2152209. Epub 2022 Dec 5. PMID: 36426912; PMCID: PMC10262765.
  • Li C, Liu Y, Liu C, Chen F, Xie Y, Zeh HJ, Yu C, Liu J, Tang D, Kang R. AGER-dependent macropinocytosis drives resistance to KRAS-G12D-targeted therapy in advanced pancreatic cancer. Sci Transl Med. 2025 Jan 29;17(783):eadp4986. doi: 10.1126/scitranslmed.adp4986. Epub 2025 Jan 29. PMID: 39879317.

2. Mechanisms of Adaptive Immune Resistance in Cancer Progression

Adaptive immune resistance is a dynamic process through which cancer cells alter their phenotype in response to cytotoxic or proinflammatory immune pressure, thereby evading immune-mediated destruction. This adaptation is typically initiated by antigen-specific recognition by T cells, followed by the release of immune-stimulating cytokines within the tumor microenvironment. Recent findings from our laboratory reveal that activation of cyclin-dependent kinases (CDK1/2/5) or heat shock protein 90 (HSP90) plays a pivotal role in driving this adaptive immune resistance in pancreatic cancer. These results suggest that therapeutic targeting of CDK1/2/5 or HSP90 may potentiate the efficacy of immune checkpoint blockade by disrupting tumor-intrinsic mechanisms of immune escape. Additionally, we have identified a novel autophagy receptor responsible for STING1 degradation, which impairs antitumor immunity by limiting cytosolic DNA sensing and type I interferon responses.

Publications: 

  • Huang J, Chen P, Liu K, Liu J, Zhou B, Wu R, Peng Q, Liu ZX, Li C, Kroemer G, Lotze M, Zeh H, Kang R, Tang D. CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer. Gut. 2021 May;70(5):890-899. doi: 10.1136/gutjnl-2019-320441. Epub 2020 Aug 14. PMID: 32816920.
  • Liu J, Zhu S, Zeng L, Li J, Klionsky DJ, Kroemer G, Jiang J, Tang D, Kang R. DCN released from ferroptotic cells ignites AGER-dependent immune responses. Autophagy. 2021 Dec 29:1-14. doi: 10.1080/15548627.2021.2008692. Epub ahead of print. PMID: 34964698.
  • Liu K, Huang J, Liu J, Li C, Kroemer G, Tang D, Kang R. HSP90 Mediates IFNγ-Induced Adaptive Resistance to Anti-PD-1 Immunotherapy. Cancer Res. 2022 May 16;82(10):2003-2018. doi: 10.1158/0008-5472.CAN-21-3917. PMID: 35247909.
  • Mender I, Siteni S, Barron S, Flusche AM, Kubota N, Yu C, Cornelius C, Tedone E, Maziveyi M, Grichuk A, Venkateswaran N, Conacci-Sorrell M, Hoshida Y, Kang R, Tang D, Gryaznov S, Shay JW. Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma. Mol Cancer Ther. 2023 Jun 1;22(6):737-750. doi: 10.1158/1535-7163.MCT-23-0039. PMID: 37070671; PMCID: PMC10233358.
  • Han L, Meng L, Liu J, Xie Y, Kang R, Klionsky DJ, Tang D, Jia Y, Dai E. Macroautophagy/autophagy promotes resistance to KRASG12D-targeted therapy through glutathione synthesis. Cancer Lett. 2024 Nov 1;604:217258. doi: 10.1016/j.canlet.2024.217258. Epub 2024 Sep 12. PMID: 39276914; PMCID: PMC11890192.
  • Zhang R, Yu C, Zeh HJ, Kroemer G, Klionsky DJ, Tang D, Kang R. TAX1BP1-dependent autophagic degradation of STING1 impairs anti-tumor immunity. Autophagy. 2025 Mar 3:1-22. doi: 10.1080/15548627.2025.2471736. Epub ahead of print. PMID: 40000606.

3. Mechanisms and Applications of Cell Death in Cancer Therapy  

Evasion of regulated cell death is a hallmark of cancer that enables malignant cells to survive under stress, resist therapeutic interventions, and sustain uncontrolled proliferation. Restoring or inducing cell death in cancer cells is therefore a fundamental objective of anticancer therapies. Traditional approaches such as chemotherapy and radiotherapy primarily activate apoptosis, a form of programmed cell death; however, many cancers acquire resistance to apoptosis through genetic alterations in TP53, BCL2 family members, or caspases. To address this challenge, our current research is focused on exploiting non-apoptotic forms of regulated cell death, including ferroptosis (iron-dependent lipid peroxidation-mediated death), cuproptosis (copper-induced mitochondrial dysfunction), and alkaliptosis (pH-dependent cell death). These alternative pathways offer promising therapeutic opportunities, particularly for apoptosis-resistant tumors. Importantly, certain forms of non-apoptotic cell death can also promote antitumor immunity by releasing DAMPs, thereby enhancing the effectiveness of immune checkpoint blockade and other immunotherapies.

Publications:

  • Song X, Zhu S, Xie Y, Liu J, Sun L, Zeng D, Wang P, Ma X, Kroemer G, Bartlett DL, Billiar TR, Lotze MT, Zeh HJ, Kang R, Tang D. JTC801 Induces pH-dependent Death Specifically in Cancer Cells and Slows Growth of Tumors in Mice. Gastroenterology. 2018 Apr;154(5):1480-1493. doi: 10.1053/j.gastro.2017.12.004. Epub 2017 Dec 14. PMID: 29248440; PMCID: PMC5880694.
  • Kuang F, Liu J, Xie Y, Tang D, Kang R. MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells. Cell Chem Biol. 2021 Jun 17;28(6):765-775.e5. doi: 10.1016/j.chembiol.2021.01.006. Epub 2021 Feb 3. PMID: 33539732.
  • Chen X, Song X, Li J, Zhang R, Yu C, Zhou Z, Liu J, Liao S, Klionsky DJ, Kroemer G, Liu J, Tang D, Kang R. Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis. Autophagy. 2022 Apr 10:1-21. doi: 10.1080/15548627.2022.2059170. Epub ahead of print. PMID: 35403545.
  • Chen X, Hung J, Yu C, Liu J, Gao W, Li J, Song X, Zhou Z, Li C, Xie Y, Kroemer G, Liu J, Tang, D, Kang R. The noncanonical function of EIF4E limits ALDH1B1 activity to increase susceptibility to ferroptosis. Nat Commun. 2022 Oct 23;13(1):6318. doi: 10.1038/s41467-022-34096-w. PMID: 36274088; PMCID: PMC9588786.
  • Li J, Liu J, Zhou Z, Wu R, Chen X, Yu C, Stockwell B, Kroemer G, Kang R, Tang D. Tumor-specific GPX4 degradation enhances ferroptosis-initiated antitumor immune response in mouse models of pancreatic cancer. Sci Transl Med. 2023 Nov;15(720):eadg3049. doi: 10.1126/scitranslmed.adg3049. Epub 2023 Nov 1. PMID: 37910602.
  • Song X, Zhou Z, Liu J, Li J, Yu C, Zeh HJ, Klionsky DJ, Stockwell BR, Wang J, Kang R, Kroemer G, Tang D. Cytosolic cytochrome c represses ferroptosis. Cell Metab. 2025 Apr 8:S1550-4131(25)00149-4. doi: 10.1016/j.cmet.2025.03.014. Epub ahead of print. PMID: 40233758.
  • Chen F, Tang H, Li C, Kang R, Tang D, Liu J. CYP51A1 drives resistance to pH-dependent cell death in pancreatic cancer. Nat Commun. 2025 Mar 7;16(1):2278. doi: 10.1038/s41467-025-57583-2. PMID: 40055353; PMCID: PMC11889236.

4. The Immunopathology of Sepsis and Potential Therapeutic Targets

My laboratory is dedicated to advancing the understanding of immunology and coagulation mechanisms in lethal infections and developing innovative anti-inflammatory strategies. Our key findings include: 1) Excessive Pyroptosis in Macrophages: We have established that heightened pyroptosis in macrophages significantly accelerates the inflammatory response in sepsis, thereby exacerbating the condition (Nature Communications, 2014, 2016; Cell Host & Microbe, 2018; Frontiers in Immunology, 2019; Science Advances, 2019). 2) Inflammasome Activation and Coagulation: Our research indicates that excessive activation of inflammasomes intensifies the coagulation response in sepsis, presenting a critical target for modulating disease outcomes (Immunity, 2018; Cell Host & Microbe, 2020). We have identified STING1/TMEM173 as a pivotal driver of immunocoagulation in sepsis and septic shock, underscoring its role in linking immune activation and coagulation processes (Science Translational Medicine, 2017; Cell Host & Microbe, 2020; Immunity, 2023). 3) Extracellular SQSTM1 and Septic Death: Our studies reveal that extracellular SQSTM1 serves as a mediator of septic death, suggesting its potential as a biomarker and therapeutic target in sepsis management (Nature Microbiology, 2020). 4) Circadian Regulation of Immune Responses: We have demonstrated that the circadian clock regulates immune checkpoint pathways in sepsis, which could influence the timing and effectiveness of therapeutic interventions (Cell Reports, 2018). These discoveries contribute significantly to our understanding of sepsis pathophysiology and offer promising avenues for developing targeted therapeutic strategies.

Publications: 

  • Zeng L, Kang R, Zhu S, Wang X, Cao L, Wang H, Billiar TR, Jiang J, Tang D. ALK is a therapeutic target for lethal sepsis. Sci Transl Med. 2017 Oct 18;9(412):eaan5689. doi: 10.1126/scitranslmed.aan5689. PMID: 29046432; PMCID: PMC5737927.
  • Kang R, Zeng L, Zhu S, Xie Y, Liu J, Wen Q, Cao L, Xie M, Ran Q, Kroemer G, Wang H, Billiar TR, Jiang J, Tang D. Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host Microbe. 2018 Jul 11;24(1):97-108.e4. doi: 10.1016/j.chom.2018.05.009. Epub 2018 Jun 21. PMID: 29937272; PMCID: PMC6043361.
  • Chen R, Zeng L, Zhu S, Liu J, Zeh HJ, Kroemer G, Wang H, Billiar TR, Jiang J, Tang D, Kang R. cAMP metabolism controls caspase-11 inflammasome activation and pyroptosis in sepsis. Sci Adv. 2019 May 22;5(5):eaav5562. doi: 10.1126/sciadv.aav5562. PMID: 31131320; PMCID: PMC6531004.
  • Zhang H, Zeng L, Xie M, Liu J, Zhou B, Wu R, Cao L, Kroemer G, Wang H, Billiar TR, Zeh HJ, Kang R, Jiang J, Yu Y, Tang D. TMEM173 Drives Lethal Coagulation in Sepsis. Cell Host Microbe. 2020 Apr 8;27(4):556-570.e6. doi: 10.1016/j.chom.2020.02.004. Epub 2020 Mar 5. PMID: 32142632; PMCID: PMC7316085.
  • Zhou B, Liu J, Zeng L, Zhu S, Wang H, Billiar TR, Kroemer G, Klionsky DJ, Zeh HJ, Jiang J, Tang D, Kang R. Extracellular SQSTM1 mediates bacterial septic death in mice through insulin receptor signalling. Nat Microbiol. 2020 Dec;5(12):1576-1587. doi: 10.1038/s41564-020-00795-7. Epub 2020 Oct 19. PMID: 33077977; PMCID: PMC7977680.
  • Wu R, Liu J, Wang N, Zeng L, Yu C, Chen F, Wang H, Billiar TR, Jiang J, Tang D, Kang R. Aconitate decarboxylase 1 is a mediator of polymicrobial sepsis. Sci Transl Med. 2022 Aug 24;14(659):eabo2028. doi: 10.1126/scitranslmed.abo2028. Epub 2022 Aug 24. PMID: 36001682.
  • Zhang R, Yu C, Zeh HJ, Wang H, Kroemer G, Klionsky DJ, Billiar TR, Kang R, Tang D. Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis. Immunity. 2023 Dec 12;56(12):2736-2754.e8. doi: 10.1016/j.immuni.2023.11.001. Epub 2023 Nov 27. PMID: 38016467; PMCID: PMC10842782.
  • Wang N, Liu J, Wu R, Chen F, Zhang R, Yu C,  Zeh HJ,  Xiao X,  Wang H,   Billiar TR, Zeng L, Jiang J,  Tang D,  Kang R. A neuroimmune pathway drives bacterial infection. Sci Adv. 2025. doi: 10.1126/sciadv.adr2226.

Publications

View a complete list of Kang Lab publications. 

Contact

  • Room H7.102A
  • UT Southwestern Medical Center
  • 5323 Harry Hines Blvd Dallas, TX 75390-9160
  • Email