Areas of Interest

Research Interests

Signaling Mechanism of Cancer-induced Fat Loss

Cancer cachexia syndrome is characterized by systemic inflammation, body weight loss, remodeling of adipose tissue, and skeletal muscle wasting. Consequently, it results in reduced quality of life, decreased survival, and increased complications due to cancer treatment. Cachexia is the main cause of death in approximately 20% to 30% of all patients with cancer. In cancer cachexia patients, impairment of adipose tissue lipid metabolism has been demonstrated and longitudinal studies have established that AT loss precedes muscular atrophy.

Toll-like receptor4 (TLR4) mediates cancer-induced muscle wasting by directly activating muscle catabolism as well as stimulating an innate immune response in mice bearing tumors, and targeting TLR4 effectively abrogate muscle wasting. We show that TLR4 has essential roles in cancer-induced adipose tissue wasting. Both genetic ablation and pharmacological inhibition of TLR4 are able to attenuate the main clinical markers of cancer-induced fat loss. We further use in vitro and in vivo models of cancer to elucidate detailed molecular mechanisms of cancer-induced fat loss, and eventually to ameliorate or reverse the syndrome.

Publications

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  • Zou S, Qin B, Yang Z, Wang W, Zhang J, Zhang Y, Meng M, Feng J, Xie Y, Fang L, Xiao L, Zhang P, Meng, X, Choi HH, Wen W, Pan Q, Ghesquiere B, Lan P, Lee MH, Fang L.  (2022).  CSN6 mediates nucleotide metabolism to promote tumor development and chemoresistance in colorectal cancer. Cancer Res, 83(3):414–42.
  • Chou PC*, Choi HH*, Huang Y, Fuentes-Mattei E, Velazquez-Torres G, Zhang F, Phan L, Lee J, Shi Y, Bankson JA, Wu Y, Wang H, Zhao R, Yeung SJ, Lee MH. (2021). Impact of diabetes on promoting the growth of breast cancer. Cancer Communications, 41(5): 414–431.
    PMCID: PMC8118590. * equally contributed 
  • Choi HH, Zou S, Wu JL, Wang H, Phan L, Li K, Zhang P, Chen D, Liu Q, Qin B, Nguyen TAT, Yeung SJ, Fang L, Lee MH. (2020). EGF relays signals to COP1 and facilitates FOXO4 degradation to promote tumorigenesis. Advanced Science.
  • Velazquez-Torres G*, Fuentes-Mattei E*, Choi HH*, Yeung SJ, Meng X, Lee MH. (2020). Diabetes mellitus type 2 drives metabolic reprogramming to promote pancreatic cancer growth. Gastroenterology Report. 8(4):261-276. * equally contributed
  • Qin B, Zou S, Li K, Wang H, Wei W, Zhang B, Xiao L, Choi HH, Tang Q, Huang D, Liu Q, Pan Q, Meng M, Fang L, Lee MH. (2020). CSN6-TRIM21 axis instigates cancer stemness during tumorigenesis. Br J Cancer. 122(11):1673-1685.
  • Choi HH and Lee MH. (2019). C-type lectin receptors as potential targets for the treatment of gastrointestinal diseases related with fungal infection. Gastroenterology Report. 7(5):376-377.
  • Ko EJ, Oh YL, Kim HY, Eo WK, Kim H, Kim KH, Koh SB, Ock MS, Choi YH, Kim A, Choi HH, Park EJ, Cha HJ. (2019). Correlation of constitutive photomorphogenic 1 (COP1) and p27 tumor suppressor protein expression in ovarian cancer. Genes & Genomics.41(8):879-884.
  • Choi HH and Lee MH.  (2019). Targeting host-microbe interaction in the mucus layer : a potential treatment option for diseases. Gastroenterology Report.  7(1):1-2.
  • Liu Y*, Xu J*, Choi HH*, Han C, Fang Y, Li Y, Van der Jeught K, Xu H, Zhang L, Frieden M, Wang L, Eyvani H, Sun Y, Zhao G, Zhang Y, Liu S, Wan J, Huang C, Ji G, Lu X, He X. Zhang X. (2018). Targeting 17q23 amplicon to overcome the resistance to anti-HER2 therapy in HER2+ breast cancer. Nature Communications. 9(1):4718.* equally contributed
  • Han C*, Yang L*, Choi HH*, Baddour J, Achreja A, Liu Y, Li Y, Li J, Wan G, Huang C, Ji G, Zhang X, Nagrath D, Lu X. (2016). Amplification of USP13 drives ovarian tumor metabolism. Nature Communications. 7:13525  * equally contributed