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Hong-Ji Xu, M.D., Ph.D.
The research of my laboratory focuses on searching for novel therapeutic genes for human cancer as well as applying knowledge about tumor suppressor genes and cytokine genes to the design of cancer gene therapy. The strengths of our comprehensive and dynamic research program lie in the novelty of its research. We are the first to successfully construct a single recombinant adenovirus vector that directs high-level and tetracycline-regulatable expression of human cytokines in a variety of human cells. Although further obstacles are to be circumvented, we believe that the availability of this type of vector may help to pave the way for predictable and controllable gene delivery. I am the primary inventor of 4 patents awarded or pending, including one pertinent to an N-terminal-truncated RB tumor suppressor gene for anticancer therapy (U.S. patent 5,496,731, 1996).

Our basic research is centered on the mechanisms of differential induction of apoptosis and senescence following expression of potential therapeutic genes in tumor cells. Recent studies done by us have also provided direct evidence for pRB-mediated cellular senescence and inhibition of telomerase activity. Thus, overexpression of pRB protein in tumor cells is sufficient to reverse their immortality, while the replicative life spans of normal cells are not affected. In this connection, we have committed ourselves to a phase I prostate cancer gene therapy clinical trial using a modified RB tumor suppressor gene. The clinical trial will take place at the Department of Genitourinary Medical Oncology with Dr. Christopher Logothetis as principal investigator of the clinical protocol. In a pilot project, we shall be able to generate preliminary data to support a new approach to cytokine gene-mediated in situ tumor vaccination for advanced cancers using transcriptionally targeted and regulatable vectors.

Selected Publications:
  1. Hu S-X, Ji W, Zhou YL, Logothetis C, Xu H-J. Development of an adenovirus vector with tetracycline-regulatable human TNF-gene expression. Cancer Res 57:3339-3343, 1997
  2. Li J, Hu S-X, Xu K, Perng G-S, Zhou Y, Xu K, Zhang C, Benedict WF, Xu H-J. Expression of the retinoblastoma (RB) tumor suppressor gene inhibits tumor cell invasion in vitro. Oncogene 13:2379-2386, 1996
  3. Xu H-J. Strategies for approaching retinoblastoma (RB) tumor suppressor gene therapy. In: August JT (ed). Gene Therapy, Advances in Pharmacology, vol 40, pp 369-397. San Diego: Academic Press, 1997
  4. Xu H-J, Zhou YL, Ji W, Perng GS, Kruzelock R, Bast RC, Mills GB, Li J, Hu S-X. Reexpression of retinoblastoma protein induces tumor cell senescence and telomerase inhibition. Oncogene 15:2589-2596, 1997
  5. Xu H-J, Zhou YL, Seigne J, Perng GS, Mixon M, Zhang CY, Li J, Benedict WF, Hu SX. Enhanced tumor suppressor gene therapy via replication-deficient adenovirus vectors expressing an N-terminal truncated retinoblastoma protein. Cancer Res 56:2245-2249, 1996