Shengkan (Victor) Jin, Ph.D.
Associate Professor
Department of Pharmacology
Robert Wood Johnson Medical School
B.S., Tsinghua University, 1992
Ph.D., Cornell University, 1999

RWJMS/Piscataway R529
Office Tel: 732-235-4329
Lab Tel: 732-235-4167
Fax: 732-235-4073
Email: jinsh@umdnj.edu

 

Research Interests:

Autophagy in cancer biology, cancer therapy, and aging control

 

Research Summary:

Humans, as well as other mammals with long life spans, face a formidable challenge: the accumulation of somatic mutations over time. These mutations often manifest themselves in various diseases, which eventually lead to the demise of the individual organism. Cancer is one of these diseases, which is caused by a combination of somatic genetic changes in a single cell that together result in uncontrolled cell growth and proliferation. In essence, cancer is an aging disease. It is not surprising that age is the single most important risk factor of cancer and many cellular processes are involved in both aging control and tumor suppression. The laboratory is focused on autophagy, an incredible new cellular process that we and others have demonstrated to play a critical role in preventing both cancer development and aging.

Autophagy is a higly regulated membrane-trafficking process leading to the lysosomal degradation (as shown in the inserted figure). During autophagy, cytoplasmic components are first sequestered in double-membrane vesicles--the autophagic vacuoles or autophagosomes. These vesicles then dock and fuse to lysosomes, where they are further degraded. It is believed that autophagic degradation plays a critical role for clearing damaged organelles and protein aggregates and is essential for the maintenance of a health cell.

 

The genes involved in autophagy, known as the autophagy-related genes (Atg), have been identified and characterized. The first autophagy gene in humans identified was named Beclin 1. Interestingly, Knocking out Beclin1 gene in mice increases cancer rates. Similarly, in humans Beclin 1 is monoallelically deleted in up to 40% of prostate cancers, 50% of breast cancers, and 75% of ovarian cancers. Part of the laboratory is working on the mechanism by which autophagy defect causes cancer. In addition, the lab is also working on pharmacologically manipulating autophagy in normal and cancer cells for tumor prevention and tumor therapy.

Autophagy is also involved in aging control. Inactivation of the beclin1 gene or other autophagy genes in C. elegans would reduce the life-spans of the worms. Apparently mitochondria, the organelles that are the major sources of intracellular reactive oxygen species (ROS) and are known to be a major contributor to aging, can only be degraded through autophagy. Part of the lab is working on how autophagy specifically degrades damaged mitochondria and how that would impact aging.

The research conducted in the lab is supported by the National Cancer Institute (NCI) and National Institute of Aging (NIA) of NIH, American Cancer Society (ACS), and the Department of Defense.

Laboratory Personnel:
Selected Publications
  1. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, White E. (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21(13):1621-35.
  2. Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, Chen G, Jin S, White E. (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 21(11):1367-81.
  3. Zhang Y, Qi H, Taylor R, Xu W, Liu LF, Jin S. (2007) The Role of Autophagy in Mitochondria Maintenance: Characterization of Mitochondrial Functions in Autophagy-Deficient S. cerevisiae Strains. Autophagy. 9;3(4)
  4. Shengkan Jin* and Eileen White. (2007) Role of Autophagy in Cancer: Management of Metabolic Stress. Autophagy 3 (1), 28-31 (* SJ is a Co- corresponding author)
  5. Jin S, Dipaola RS, Mathew R, White E. (2007). Metabolic catastrophe as a means to cancer cell death. J Cell Sci.120:379-83.
  6. Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, Levine AJ. (2007) The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 67(7):3043-53.
  7. Eszter S. Hars, Haiyan Qi, Shengkan Jin, Li Cai, Chengcheng Hu and Leroy F. Liu. (2007). Autophagy Regulates Ageing in C. elegans. Autophagy. 3(2):93-5
  8. Shengkan Jin. (2006) Autophagy, Mitochondria Quality Control, and Oncogenesis. Autophagy. 2(2): 80-84. [Full Text PDF]
  9. Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D, Chen, G., Mukherjee, C., Shi, Y., Nelson, D.A., Jin, S., and White, E. (2006). Autophagy Promotes Tumor cell Survival and Restricts Necrosis, Inflammation, and Tumorigenesis. Cancer Cell. 10(1):51-64
  10. Arnold J. Levine, Zhaohui Feng, Tak W. Mak, Han You, and Shengkan Jin.(2006) Coordination and Communication between the p53 and IGF-1-AKT-TOR Signal Transduction Pathways. Genes and Development. 20 (3): 267-75. [Full Text PDF]
  11. Haiyan Zhang, Claude E. Monken, John Lenard, Noboru Mizushima, Edmund C. Lattime, and Shengkan Jin. (2006) Cellular Autophagy Machinery is not Required for Vaccinia Virus Replication and Maturation. Autophagy, 2(2): 91-95. [Full Text PDF]
  12. Changyou Li, Elizabeth Capan, Yani Zhao, Jianping Zhao, Donna Stolz, Simon C. Watkins, Shengkan Jin and Binfeng Lu. (2006) Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J. Immunology. 177(8):5163-8
  13. William N. Hait, Hao Wu, Shengkan Jin and Jin-Ming Yang. (2006). Elongation Factor-2 Kinase: Its Role in Protein Synthesis and Autophagy. Autophagy, 2 (4).
  14. William N. Hait, Shengkan Jin and Jin-Ming Yang. (2006) A Matter of Life and Death (or Both): Understanding Autophagy in Cancer. Clinical Cancer Research. 12:1961-5.
  15. Wu H, Yang JM, Jin S, Zhang H, and Hait WN. (2006) Elongation factor-2 kinase regulates autophagy in human glioblastoma cells. Cancer Research. 66(6):3015-23.
  16. Zhaohui Feng, Shengkan Jin*, A. Zupnick, J. Hoh, E. de Stanchina, S. Lowe, C. Prives, and Arnold J. Levine. (2006) p53 tumor suppressor protein regulates the levels of huntingtin gene expression. (*S.J. is an equal contribution first author). Oncogene. 25(1):1-7 [Full Text PDF]
  17. Shengkan Jin. (2005) p53, Autophagy, and Tumor Suppression. Autophagy. 1 (3). 34-36. [Full Text PDF].
  18. Feng Z, Zhang H, Levine AJ, Jin S. (2005) The coordinate regulation of the p53 and mTOR pathways in cells.Proc Natl Acad Sci. 102(23):8204-9. [Full Text PDF]
  19. Zhenyu Yue, Shengkan Jin, Chingwen Yang, Arnold J. Levine, Nathaniel Heintz. (2003). Beclin1, an autophagy gene essential for early embryo development, is a tumor suppressor. Proc. Nat. Acad. Sci. 100 (25): 15077-15082 [ Abstract | Full Text PDF ]
  20. Shengkan Jin, Markus Kalkum, Michael Overholtzer, Archontoula Stoffel, Brian T. Chait and Arnold J. Levine. (2003) CIAP1 and the Serine Protease HTRA2 are Involved in a Novel p53-dependent Apoptotic Pathway in Mammals. Genes and Development 17:359-367. [ Abstract | Full Text PDF ]
  21. J. Hoh, S. Jin*, T. Parrado, J. Edington, A. J. Levine, J. Ott (*S. Jin is a co-first author). (2002) The p53MH algorithm and its application in detecting p53-responsive genes. Proc. Nat. Acad. Sci. 99 (13): 8467-8472. [ Abstract | Full Text PDF ]
  22. Shengkan Jin and Arnold J. Levine. (2001) p53 Function Circuit. Journal of Cell Science 114 ( 23): 4139-40. [ Abstract | Full Text PDF ]
  23. Shengkan Jin, Sebastian Martinek, Jennifer R. Wortman, Woo S. Joo, Nebojsa Mirkovic, Andrej Sali, Nikola P. Pavletich, Mark D. Yandell, Michael W. Young and Arnold J. Levine. (2000) Identification and Characterization of a p53 Homologue in Drosophila melanogaster. Proc. Nat. Acad. Sci. Vol. 97 (13): 7301-7306. [ Abstract | Full Text PDF ]
  24. Shengkan Jin, Barbara Gorfajn, Glynn Faircloth and Kathleen W. Scotto. (2000) Ecteinascidin 743, an Antitumor Agent with Novel Mechanism, Inhibits the Transcriptional Activation of the MDR1Gene. Proc. Nat. Acad. Sci. Vol. 97 (12): 6775-6779. [ Abstract | Full Text PDF ]
  25. Zhen Hu, Shengkan Jin and Kathleen W. Scotto. (2000) Transcriptional Activation of the MDR1 Gene by UV Irradiation: Role of NF-Y and SP1. Journal of Biological Chemistry. Vol. 275(4): 2979-2985. [ Abstract | Full Text PDF ]
  26. Shengkan Jin and Kathleen W. Scotto. (1998) Transcriptional Regulation of the MDR1 Gene by Histone Acetyltransferase and Histone Deacetylase is mediated by NF-Y. Molecular and Cellular Biology. Vol. 18 (7): 4377-4384. [ Abstract | Full Text PDF ]
Lab Positions Available:

The lab has several positions available for motivated postdoctoral fellow, technician, and graduate student.

Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey