Houjian Cai, Ph.D.

Pharmaceutical and Biomedical Sciences
Associate Professor

Pharmaceutical and Biomedical Sciences

Education

Ph.D., Microbiology, University of Tennessee (UT), 2006

Post Doctoral Fellow, Prostate cancer Biology, University of California Los Angeles, 2011

Areas of Expertise

Extracellular vesicles for protein delivery;

Protein myristoylation/lipidation regulate tumorigenic activity in prostate cancer;

Fatty acid metabolism in regulation of prostate cancer progression;

Epithelial-Stromal interaction in prostate cancer;

Targeting AR signaling.

Honors, Awards, and Achievements
  • Department of Defense, postdoctoral fellow training award, 2008-2009
  • Science Alliance Award for Outstanding Scholarly Achievement, UTK, 2006
  • Omicron Delta Kappa National Leadership Honor Society, 2006
Affiliations
  • International Society for Extracellular Vesicles
  • Society for Basic Urologic Research
  • American Society for Biochemistry and Molecular Biology
  • American Association for Cancer Research
Research Interests

The goal of my lab is to interrogate the molecular mechanisms in facilitation of tumor progression and provide the scientific rationale for cancer treatment. Numerous oncogenic proteins require fatty acyl modifications to carry out their functions in cancer cells.  Protein acylation, including myristoylation and palmitoylation, is particularly essential for leading these proteins to the correct location at the cytoplasmic membrane, thereby facilitating molecular functions. We use state-of-the-art techniques to:

  1. Manufacture extracellular vesicles encapsulating CRISPR machinery for treatment of prostate cancer. We have developed a novel strategy to encapsulate the CRISPR Cas9/sgRNA ribonucleoprotein (RNP) complexes into extracellular vesicles. This project is to silence oncogenic event as a single therapy for treatment of cancers including castration resistant prostate cancer.
  2. Investigate how protein acylation regulates oncogenic signaling and tumor progression. High fat diets provide a tremendous source of fatty acids for the acceleration of oncogenic signaling. This project is to understand the molecular mechanisms behind if and how high fat diets are associated with cancer progression.
  3. Investigate molecular mechanisms of how protein acylation facilitates tumorigenesis, and identify therapeutic approaches of targeting protein acylation for cancer treatment. The expression and activity of enzymes that facilitate protein acylation are usually elevated in cancers. We are working to identify lead compounds that exhibit biological efficacy in the inhibition of protein acylation and thereby cancer progression. This project will allow us to develop potential drugs for chemotherapy.
Selected Publications
  1. Yongjie Ma, Junyi Zha, XiangKun Yang, Qianjin Li, Qingfu Zhang, Amelia Yin, Zanna Beharry, Hanwen Huang, Jiaoti Huang, Michael Bartlett, Kaixiong Ye, Hang Yin, Houjian Cai (2021). Long chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation, Oncogene, 40:1806-1820.
  2. Yongjie Ma, Xiaohan Zhang, Essilvo Sulejmani, Junyi Zha, Zanna Beharry, Hanwen Huang, Michael Bartlett, Zachary Lewis, Houjian Cai. (2020) Long-chain acyl-CoA synthetase 4-mediated fatty acid metabolism sustains androgen receptor pathway-independent prostate cancer. Molecular Cancer Research. DOI:1158/1541-7786
  3. Rai S, Alsaidan OA, Yang H, Cai H*, Wang L*. (2019) Heparan sulfate inhibits transforming growth factor β signaling and functions in cis and in trans to regulate prostate stem/progenitor cell activities. 2019, Dec 12; PMID: 31829419 (*co-corresponding author)
  4. Sungjin Kim, Xiangkun Yang, Amelia Yin, Junyi Zha, Zanna Beharry, Aiping Bai, Alicja Bielawska, Michael G. Bartlett, Hang Yin, Houjian Cai. (2019) Dietary palmitate cooperates with Src kinase to promote prostate tumor progression. Prostate, Jun;79(8):896-908.
  5. Qianjin Li, Omar A Alsaidan, Sumit Rai, Meng Wu, Huifeng Shen, Zanna Beharry, Martin E. Fernandez-Zapico, Lianchun Wang, Houjian Cai. (2018) Stromal Gli signaling regulates the activity and differentiation of prostate stem and progenitor cells, JBC, May 17. PMID: 29773652
  6. Qianjin Li, Omar Awad Alsaidn, Yongjie Ma Sungjin Kim, Junchen Liu, Thomas Albers, Kebin Liu, Zanna Beharry, Shaying Zhao, Fen Wang, Iryna Lebedyeva, Houjian Cai (2018) Pharmacologically targeting the myristoylation of the scaffold protein FRS2α inhibits FGF/FGFR-mediated oncogenic signaling and tumor progression, Journal of Biological Chemistry, 293(17):6434-6448. PMC5925806
  7. Essilvo Sulejmani and Houjian Cai (2018) Targeting protein myristoylation for the treatment of prostate cancer, Oncoscience, 5(1-2):3-5 (mini-review).
  8. Qianjin Li, Lishann Ingram, Zanna Beharry, A Cooper, Houjian Cai. (2018) Paracrine Fibroblast Growth Factor Initiates Oncogenic Synergy with Epithelial FGFR/Src Transformation in Prostate Tumor Progression, Neoplasia, 20(3):233-243. PMC5814375
  9. Sungjin Kim, Omar Awad Alsaidan, Octavia Goodwin, Qianjin Li, Zhen Han, Aiping Bai, Thomas Albers, Zanna Beharry, George Zheng, James S. Norris, Zdzislaw M. Szulc, Alicja Bielawska, Iryna Lebedyeva, Scott D. Pegan, Houjian Cai. (2017) Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression. Cancer Research, 77(24):6950-62. PMC5732839
  10. Sungjin Kim, Xiangkun Yang, Qianjin Li, Meng Wu, Leah Costyn, Zanna Beharry, Alicja Bielawska, Michael G. Bartlett, Houjian Cai (2017). Myristoylation of Src kinase mediates Src-induced and high-fat diet-accelerated prostate tumor progression in mice, Journal of Biological Chemistry, 292(45):18422-18433. PMC5682955
  11. Xiangkun Yang, Yongjie Ma, Ning Li, Houjian Cai, and Michael G. Bartlett (2017). Development of a Method for the Determination of Acyl-CoA Compounds by Liquid Chromatography Mass Spectrometry to Probe the Metabolism of Fatty Acids. Analytical Chemistry, 89 (1):813–821. PMC5679003
  12. Meng Wu, Qianjin Li, Ezequiel J. Tolosa, Lishann Ingram, Sungjin Kim, Demetri D. Spyropoulos, Zanna Beharry, Martin E. Fernandez-Zapico, Houjian Cai (2016). Gli Transcription Factors Mediate the Oncogenic Transformation of Prostate Basal Cells Induced by a Kras-Androgen Receptor Axis. Journal of Biological Chemistry, 291(49): 25749-25760. PMC5207270
  13. Verweij FJ, de Heus C, Kroeze S, Cai H, Kieff E, Piersma SR, Jimenez CR, Middeldorp JM, Pegtel DM. (2015). Exosomal sorting of the viral oncoprotein LMP1 is restrained by TRAF2 association at signalling endosomes. J Extracell Vesicles, 4:26334. PMC4394166
  14. Houjian Cai, Sanaz Memarzadeh, Tanya Stoyanova, Andrew S Kraft, Owen Witte 2012 Collaboration of Kras and AR signaling promotes EZH2 expression and proliferation of tumor propagating cells in prostate cancer. Cancer Research, 72(18):4672-4681 (Corresponding author).
  15. Houjian Cai, Daniel A. Smith, Sanaz Memarzadeh, Clifford A. Lowell, Jonathan Cooper, and Owen N. Witte, Differential transformation capacity of Src Family Kinases during the initiation of prostate cancer, Proc Natl Acad Sci USA, 2011. Apr 19; 108(16):6579-84.
  16. Houjian Cai, Ivan Babic , Xiao Wei , Jiaoti Huang, Owen N. Witte 2011 Invasive prostate carcinoma driven by c-Src and androgen receptor synergy, Cancer research, 71(3): 862-872.
  17. Stoyanova T, Goldstein AS, Cai H,  Drake JM, Huang J, Witte ON, Regulated Proteolysis of Trop2 Drives Epithelial Hyperplasia and Stem Cell Self-Renewal via β-catenin Signaling. Genes and Development, 2012, 15;26(20):2271-85.
  18. Mulholland DJ, Tran LM, Li Y, Cai H, Morim A, Wang S, Plaisier S, Garraway IP, Huang J,  Graeber TG, Wu H, Cell Autonomous Role of PTEN in Regulating Castration-Resistant Prostate Cancer Growth, Cancer cell, 2011 Jun 14; 19(6):792-804.
  19. Justin M. Drake, Nicholas A. Graham, Tanya Stoyanova, Amir Sedghi, Andrew S. goldstein, Houjian Cai, Daniel A. Smith, Hong Zhang, Evangelia Komisopoulou, Jiaoti Huang, Thomas G. Graeber, and Owen N. Witte, Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression, Proc Natl Acad Sci USA, 2012. Jan 31;109(5):1643-1648.
  20. Sanaz Memarzadeh, Houjian Cai, Deanna Janzen, Li Xin, Rita Lukacs, Mireille Riedinger, Yang Zong, Karel De Gendt, Guido Verhoeven, Jiaoti Huang, Owen N. Witte, Role of autonomous androgen receptor signaling in prostate cancer initiation is dichotomous and dependent on the oncogenic signal, Proc Natl Acad Sci USA, 2011 May 10;108(19):7962-7.
Grant Support
  • National Institutes of Health
  • The Georgia Research Alliance
  • American Institute for Cancer Research
  • Regenerative Engineering & Medicine Center, Georgia

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