He Research

Fedoroff M, Zhao L, Wang S, Bhushan A, Yang H, Bussard K, Peiper S, He J*. Amino acid transporter LAT1 (SLC7A5) promotes metabolic rewiring in TNBC progression through the L-Trp/QPRT/NAD+ pathway. J Exp Clin Cancer Res. 2025. July 3; 44 (1):190.

L-type amino acid transporter 1 (LAT1) is a cross-membrane transporter that functions in uptake of large neutral amino acids into cells. Importantly, LAT1 is regarded as a cancer-specific amino acid transporter with its protein expression predominantly localized to the plasma membrane of cancer cells, which makes LAT1 a promising molecular target for cancer treatment. In this study, we identified that the inhibition of LAT1 through a small molecule inhibitor JPH203 effectively suppresses cell proliferation, migration, and tumor growth in TNBC model. Mechanistically, we found LAT1 promotes NAD+ de novo synthesis for glycolysis through its substrate L-Tryptophan and a rate limiting enzyme QPRT expression.

Li X, Wang S, Mu W, Barry J, Han A, Carpenter RL, Jiang BH, Peiper SC, Mahoney MG, Aplin AE, Ren H, He J*. Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway. J Exp Clin Cancer Res. 2022 Jan 27; 41(1):41.

Our findings demonstrate a novel mechanism, ROS-induced down-regulation of miR-155-5p, by which tumors modulate the microenvironment in favor of tumor progression. Understanding the negative impact of ROS on the tumor immune response will improve current therapeutic strategies. Targeting miR-155-5p can be an alternative approach to prevent formation of an immunosuppressive TME through downregulation of PD-L1 and other immunosuppressive factors.

Ge X*, He J*, Wang L, Zhao L, Wang Y, Wu G, Liu W, Shu Y, Gong W, Ma XL, Wang Y, Jiang BH, Liu LZ. Epigenetic alterations of CXCL5 in Cr (VI)-induced carcinogenesis. Sci Total Environ. 2022 Sep 10; 838:155713. *co-first author

Through a population-based cross-sectional study, we identified that the expression levels of CXCL5 were highly upregulated in PBMCs samples from workers with occupational exposure to Cr (VI) compared with those in control subjects, and the CXCL5 levels were positively correlated with total Cr concentrations in subjects' toenails. Mechanistic studies showed that elevated CXCL5 expression levels were regulated by Cr (VI)-induced histone modifications and DNA hypomethylation, and that the c-Myc/p300 complex was a key upstream regulator of histone H3 acetylation. CXCL5 overexpression promoted Cr(VI)-induced EMT by upregulating zinc finger E-box binding homeobox 1 (ZEB1) to promote tumor development.

Shen H, Wang GC, Li X, Ge X, Wang M, Shi ZM, Bhardwaj V, Wang ZX, Zinner RG, Peiper SC, Aplin AE, Jiang BH, He J*. S6K1 blockade overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer. Oncogene, 2020, October 9.

In this study, we identified S6K1/MDM2 signaling axis as a novel bypass mechanism for the development of EGFR-TKI resistance. The observation of S6K1 as a candidate mechanism for resistance to EGFR TKI therapy was investigated by interrogation of public databases and a clinical cohort to establish S6K1 expression as a prognostic/predictive biomarker. The role of S6K1 in TKI resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models. Blockade of S6K1 by a specific inhibitor PF-4708671 synergistically enhanced the efficacy of TKI without showing toxicity. The mechanistic study showed the inhibition of EGFR caused nuclear translocation of S6K1 for binding with MDM2 in resistant cells. MDM2 is a downstream effector of S6K1-mediated TKI resistance. 

Complete list of published work in Dr. He's bibliography: