Prof. in Blood Cancers and Immunotherapy, Cell Biology

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center

Institute of Infection and Immunity, Translational Medicine Institute, Xi’an Jiaotong University Health Science Center

Email: jinsong.hu@xjtu.edu.cn

Tel: +86-187 1090 5160

Wechat:

ORCID:0000-0003-0565-4567 

I first became captivated by the complexities of cancer and immunology during my undergraduate degree at Shaanxi Normal Univeirsity, which led me to a PhD in Prof Zhinan Chen’s lab at the Fourth Military Medical University (Xi’an China) investigating roles of CD147 in T cell biology, and roles of the ER stress signaling pathways in protecting multiple myeloma (MM) cells from proteasome inhibitors-induced death in Prof. Karin Vanderkerken's lab at Virje Universiteit Brussel(Free University of Brussels, Brussels, Belgium). I retained a keen interest in NK (Natural killer) cell-based immunotherapy for MM during my postdoctoral research in Prof. Michale O’Dwuer's lab at the University of NUIG in Ireland, by collaborating with a  startup biotechnology company ONK Therapeutics. It was during this time in we developed novel NK cell immunotherpy options for blood cancers. This research led to one of the first PCT patent to improve NK cell ability to kill cancer cells.

Since 2014, I have secured two National Natural Science Foundation of China Awards to study drug resistance mechanisms of MM cells, and the bone protection/formation roles of proteasome inhibitors in MM. And, secured one international grant supported by ONK Therapeutics to study the effects of tumor microenvironment factors on NK cells. During COVID-19 pandemic, I also COVID-19 committed to the studies of the immunopathology of SARS-CoV 2, with support of XJTU-QINLONG grant.

My research topics are at the forefront of MM, NK cells fileds, and have published high impact studies. We were the first to characterize bone marrow tumor hypoxia can be target for MM therapy (Blood, 2010, 2012; Molecular Cancer Therapy, 2014). Our research has also made key contributions for understanding the drug resistance mechanisms of MM cells to proteasome inhibitors, and the  mechanisms of proteasome inhibitor-induced osteogenesis (Blood,2012; Stem Cell & Therapy, 2020). Focusing on the effects of tumor hypoxia, we dissected the cells signaling changes that impairing NK cytotoxicity (Journal of Immunology Research, 2020). In 2021, we published two highlighted articles in Journal of Leukocyte Biology, discovered that hyperactivated peripheral blood monocytes is the key determinant of the severity of COVID-19.

1. Pathology of multiple myeloma and drug resistance mechanisms: multiple myeloma is the second most frequent hematological malignancy. Although significant survival improvements in the years have been seen, relapsed/refractory is still very challenging, with poor response rates and no chance for cure. Drug resistance is the leading cause of a relapsed/refractory disease, and it can ultimately decrease survival. MM patients can develop drug resistance after a few cycles of therapy in a variable manner.Our data show that the activation of autophagy, especially mitophagy and ER-phagy, are important for the developing of drug resistance. We are investigating how mitophagy and ER-phagy work with ER stress signaling to modulate MM cell survival.

2. NK-based immunotherapy for cancers: our immune system is important for our health protecting us from infection/cancer, but inappropriate immune responses cause us harm. My research group wants to understand how to control immune cells and is now revealing the importance of cellular metabolism. We are revealing novel strategies to modulate immune cell function through targeting cellular metabolism and new therapeutic opportunities are being explored. Our data show following activation NK cells, with important anti-cancer and anti-viral functions, undergo robust metabolic changes.We are exploring how NK cell metabolism might be manipulated to improve NK cell-based anti-cancer immunotherapies.

3. Antiviral Immunology

2022

1. Shang Y, Jin Y, Liu H, Ding L, Tong X, Tu H, Zang L, Lin C, Hu J, Zhou F. Evaluation of prognostic staging systems of multiple myeloma in the era of novel agents. Hematol Oncol. 2022 Apr;40(2):212-222.

2021

1. Liu R, Shen Y, Hu J, Wang X, Wu D, Zhai M, Bai J, He A. Comprehensive Analysis of m6A RNA Methylation Regulators in the Prognosis and Immune Microenvironment of Multiple Myeloma. Front Oncol. 2021 Nov 4;11:731957. doi: 10.3389/fonc.2021.731957.
2. Wu D, Miao J, Hu J, Li F, Gao D, Chen H, Feng Y, Shen Y, He A. PSMB7 Is a Key Gene Involved in the Development of Multiple Myeloma and Resistance to Bortezomib. Front Oncol. 2021 Jul 23;11:684232. doi: 10.3389/fonc.2021.684232.
3. Shen Y, Feng Y, Li F, Jia Y, Peng Y, Zhao W, Hu J, He A. lncRNA ST3GAL6AS1 promotes invasion by inhibiting hnRNPA2B1mediated ST3GAL6 expression in multiple myeloma. Int J Oncol. 2021 Apr;58(4):5.
4. Wang J, Xu Y, Zhang X, Wang S, Peng Z, Guo J, Jiang H, Liu J, Xie Y, Wang J, Li X, Liao J, Wan C, Yu L, Hu J, Liu B, Liu Z. Leptin correlates with monocytes activation and severe condition in COVID-19 patients. J Leukoc Biol. 2021 Jul;110(1):9-20. (Highlighted)
5. Lei L, Zhang Y, Jian Q, Lei L, Lv N, Williamson RA, Chen P, Zhang D, Hu J. Resistance of osteosarcoma cells to the proapoptotic effects of carfilzomib involves activation of mitogen activated protein kinase pathways. Exp Physiol. 2021 Feb;106(2):438-449.
6. Zhang D, Guo R, Lei L, Liu H, Wang Y, Wang Y, Qian H, Dai T, Zhang T, Lai Y, Wang J, Liu Z, Chen T, He A, O'Dwyer M, Hu J. Frontline Science: COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes. J Leukoc Biol. 2021 Jan;109(1):13-22. (Highlighted)

2020

1. Zhang D, De Veirman K, Fan R, Jian Q, Zhang Y, Lei L, Evans H, Wang Y, Lei L, Wang B, Williamson RA, Chantry A, He P, Li A, De Raeve H, Vanderkerken K, He A, Hu J. ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation. Stem Cell Res Ther. 2020 Nov 30;11(1):516.
2. Teng R, Wang Y, Lv N, Zhang D, Williamson RA, Lei L, Chen P, Lei L, Wang B, Fu J, Liu X, He A, O'Dwyer M, Hu J. Hypoxia Impairs NK Cell Cytotoxicity through SHP-1-Mediated Attenuation of STAT3 and ERK Signaling Pathways. J Immunol Res. 2020 Jun 19;2020:4598476.
3. Yang X, Dai T, Zhou X, Qian H, Guo R, Lei L, Zhang X, Zhang D, Shi L, Cheng Y, Hu J, Guo Y, Zhang B. Naturally activated adaptive immunity in COVID-19 patients. J Cell Mol Med. 2020 Nov;24(21):12457-12463.
4. Lei L, Qian H, Yang X, Zhang X, Zhang D, Dai T, Guo R, Shi L, Cheng Y, Zhang B, Zhou X, Hu J, Guo Y. The phenotypic changes of gamma-delta T cells in COVID-19 patients. J Cell Mol Med. 2020 Oct;24(19):11603-11606.
5. Zhang D, Teng R, Lv N, Lei L, Wang Y, Williamson RA, Chen P, Gao P, O'Dwyer M, Li A, Hu J. A novel CD2 staining-based flow cytometric assay for assessment of natural killer cell cytotoxicity. J Clin Lab Anal. 2020 Dec;34(12):e23519.
6. Zhang D, Teng R, Lv N, Lei L, Wang Y, Williamson RA, Chen P, Gao P, O'Dwyer M, Li A, Hu J. A novel CD2 staining-based flow cytometric assay for assessment of natural killer cell cytotoxicity. J Clin Lab Anal. 2020 Dec;34(12):e23519.
7. Wang H, Lei L, Hu J, Li Y. Oncostatin M upregulates Livin to promote keratinocyte proliferation and survival via ERK and STAT3 signalling pathways. Exp Physiol. 2020 Jul;105(7):1151-1158.
8. Peng Y, Li F, Zhang P, Wang X, Shen Y, Feng Y, Jia Y, Zhang R, Hu J, He A. IGF-1 promotes multiple myeloma progression through PI3K/Akt-mediated epithelial-mesenchymal transition. Life Sci. 2020 May 15;249:117503.
9. Huang L, Wang Y, Bai J, Yang Y, Wang F, Feng Y, Zhang R, Li F, Zhang P, Lv N, Lei L, Hu J, He A. Blockade of HSP70 by VER-155008 synergistically enhances bortezomib-induced cytotoxicity in multiple myeloma. Cell Stress Chaperones. 2020 Mar;25(2):357-367.
10. Huang LJ, Shen Y, Bai J, Wang FX, Feng YD, Chen HL, Peng Y, Zhang R, Li FM, Zhang PH, Lei XR, Xue F, Ma YP, Hu JS, He AL. High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma. Acta Haematol. 2020;143(3):279-288.
11. Sarkar S, Chauhan SKS, Daly J, Natoni A, Fairfield H, Henderson R, Nolan E, Swan D, Hu J, Reagan MR, O'Dwyer M. The CD38low natural killer cell line KHYG1 transiently expressing CD16F158V in combination with daratumumab targets multiple myeloma cells with minimal effector NK cell fratricide. Cancer Immunol Immunother. 2020 Mar;69(3):421-434.

2019

1. Jia X, Zhao Q, Zhang Y, Dong Y, Lei L, Williamson RA, Lei Y, Tan X, Zhang D, Hu J. Identification of a Five-CpG Signature with Diagnostic Value in Thyroid Cancer. J Comput Biol. 2019 Dec;26(12):1409-1417.
2. Zhang D, Cui G, Sun C, Lei L, Lei L, Williamson RA, Wang Y, Zhang J, Chen P, Wang A, Fan R, Han S, Wang Y, Hu J. Hypoxia promotes osteosarcoma cell proliferation and migration through enhancing platelet-derived growth factor-BB/platelet-derived growth factor receptor-b axis. Biochem Biophys Res Commun. 2019 Apr 30;512(2):360-366.

2018 - 2010 （Selected）

1. Zhu M, Tian Y, Zhang H, Ma X, Shang B, Zhang J, Jiao Y, Zhang Y, Hu J, Wang Y. Methylphenidate ameliorates hypoxia-induced mitochondrial damage in human neuroblastoma SH-SY5Y cells through inhibition of oxidative stress. Life Sci. 2018 Mar 15;197:40-45.
2. Hu J, Van Valckenborgh E, Dehui X, Menu E, De Raeve H, De Bruyne E, Xu S, Van Camp B, Handisides D, Hart CP, Vanderkerken K. Synergistic induction of apoptosis in multiple myeloma cells by bortezomib and hypoxia-activated prodrug TH-302, in vivo and in vitro. Mol Cancer Ther. 2013;12(9):1763-1773.  
3. Xu D, Hu J, Xu S, De Bruyne E, Menu E, Van Camp B, Vanderkerken K, Van Valckenborgh E. Dll1/Notch activation accelerates multiple myeloma disease development by promoting CD138+ MM-cell proliferation. Leukemia. 2012;26(6):1402-5.      
4. Azab AK, Hu J, Quang P, Azab F, Pitsillides C, Awwad R, hompson B, Maiso P, Sun JD, Hart CP, Roccaro AM, acco A, Ngo HT, Lin CP, Kung AL, Carrasco DR, Vanderkerken K, Ghobrial IM. Hypoxia promotes dissemination of multiple myeloma through acquisition of endothelial to mesenchymal transition-like features. Blood. 2012;119(24):5782-94.    
5. Xu D, Hu J, Bruyne ED, Menu E, Schots R, Vanderkerken K, Van Valckenborgh E. Dll1/Notch activation contributes to bortezomib resistance by upregulating CYP1A1 in multiple myeloma. Biochem Biophys Res Commun. 2012;428(4):518-24.     
6. Xu S, Evans H, Buckle C, De Veirman K, Hu J, Xu D, Menu E, De Becker A, Vande Broek I, Leleu X, Camp BV, Croucher P, Vanderkerken K, Van Riet I. Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway. Leukemia. 2012;26(12):2546-9.
7. Hu J, Van Valckenborgh E, Menu E, De Bruyne E, Vanderkerken K. Understanding the hypoxic niche of multiple myeloma: therapeutic implications and contributions of mouse models. Dis Model Mech. 2012;5(6):763-71.            
8. Hu J, Dang N, Menu E, De Bryune E, Xu D, Van Camp B, Van Valckenborgh E, Vanderkerken K. Activation of ATF4 mediates unwanted Mcl-1 accumulation by proteasome inhibition. Blood. 2012;119(3):826-37.    
9. Hu J, Dang N, Song T, Vanderkerken K. Mcl-1 reduction due to caspase-dependent cleavage during endoplasmic reticulum stress-induced apoptosis. J Biol Chem. 2011;286(44):le24.  
10. Hu J, Handisides DR, Van Valckenborgh E, De Raeve H, Menu E, Vande Broek I, Liu Q, Sun JD, Van Camp B, Hart CP, Vanderkerken K. Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrug. Blood. 2010;116(9):1524-7.     

1. Teaching courses

（1）Cell biology (graduate course)

（2）Medical genetics (graduate course)

（3）Medical genetics (postgraduate course)

2. Textbook author

（1）Medical Cell Biology (4th edition), (ISBN 978-7-04-051711-8)（2019）

（2）Medical Cell Biology (4th edition), (ISBN 978-7-03-061547-3 )（2019）

（3）Medical Genetics (4th edition), (ISBN 978-7-5659-1780-6)（2018）

（4）Medical Genetics (4th edition),(ISBN 978-7-117-26939-1)（2018）

（5）Medical Biology (9th edition),(ISBN 978-7-117-26344-3)（2018）

胡劲松，（双）博士、教授。

西安交通大学医学部基础医学院细胞生物学与遗传学系、西安交通大学医学部转化医学研究院感染与免疫研究所PI。

西安交通大学医学部基础医学院基础医学实验教学中心副主任。

主要从事恶性血液肿瘤、NK细胞免疫治疗血液肿瘤、抗病毒免疫机制方面的研究。既往研究成功解析了多发性骨髓瘤骨髓微环境特征、蛋白酶体抑制剂耐药以及促成骨发生机制，以及COVID-19单核细胞过度活化的免疫病理机制，相关成果发表在专业领域权威期刊Blood, Leukemia, Stem Cell Research & Therapy,Journal of Leukocyte Biology等。以第一作者或通讯作者共发表论文30余篇，被引用>1200次，H index=16。在NK细胞肿瘤免疫领域获得国际专利授权1项，国家专利授权4项。

主持国家自然科学基金面上项目2项、国际合作项目1项、省部级课题3项。