Stressing Out Therapy Resistant Cancers

Speaker

Xi Chen Ph.D.

Baylor College of Medicine

• Baylor College of Medicine Associate Professor
• Cullen Duncan McAshan Endowed Chair in Cancer Research

About Dr. Chen:

Dr. Chen Xi is an Associate Professor at Baylor College of Medicine and holds the Cullen Duncan McAshan Endowed Chair in Cancer Research. The Chen laboratory specializes in studying the function and mechanism of the Endoplasmic Reticulum (ER) protein quality control machinery in cancer progression, metastasis, and therapy resistance. They also have expertise in ER stress, Unfolded Protein Response (UPR), biochemistry, transgenic and preclinical animal models, as well as cancer biology and immunology.

Dr. Chen's research aims to understand the molecular mechanisms underlying oncogenic signaling, regulated proteostasis, and their significance in cancer progression, therapy resistance, and anti-tumor immunity. They are dedicated to developing mechanism-based novel therapies to overcome therapy resistance and transform cancer into a manageable chronic disease (Nat Rev Cancer, 2021).

In a recent study published in JCI, the Chen laboratory revealed the critical role of the IRE1a/XBP1 branch of the UPR in mediating chemotherapy resistance. This discovery has led to the initiation of the first-in-human clinical trial of an IRE1a RNase inhibitor.

Another research focus of the Chen laboratory is on ER Associated Degradation (ERAD). They recently made a significant discovery regarding the crosstalk between the ERAD complex and UPR in maintaining proteostasis and niche interactions (Nat Cell Biol, 2020; eLife, 2021).

Selected Publications:

[1] Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors. Science. 2023 Sep 8;381(6662)

[2] Protein quality control through endoplasmic reticulum-associated degradation maintains haematopoietic stem cell identity and niche interactions. Nat Cell Biol. 2020 Oct 22;22(10):1162-1169.

[3] Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer. J Clin Invest. 2018;128(4):1283-1299.

[4] Endoplasmic reticulum stress signals in the tumour and its microenvironment. Nat Rev Cancer. 2020 Nov 19

[5] Notch-induced endoplasmic reticulum-associated degradation governs mouse thymocyte β-selection. eLife. 2021 Jul 9

Learn More

https://www.bcm.edu/people-search/xi-chen-19356