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John T. Isaacs, PhD

Department Affiliations Department of Oncology, Department of Urology, Co-Director, Pharmacology and Drug Development Program, Co-Director, Urologic Oncology Program
Rank Professor
Office Phone 410-955-7777
Lab Phone
Fax 410-614-8397
SOM Address Room 1M44 Cancer Research Building I

Jin Gao  1994 – 2000

Annastashia Mhaka  1999 – 2004

Ivan Litvinov 2000 – 2006

Research Interests

How and why cells undergo energy dependent cellular suicide, termed programmed cell death or apoptosis, is just as regulated and complicated as how and why cells proliferate. The laboratory is defining the cascade of cellular and molecular events involved in PCD using normal and malignant prostate cells as model systems. These studies are focused upon identifying potential therapeutic mechanisms for activating this PCD pathway as a new and more effective approach to prostate cancer therapy.

Prostate gland and prostate cancer cells that have metastasized to other tissues are known to secrete multiple proteases including PSA, PMSA, hK2 and others. Our lab is trying to take advantage of the aforementioned fact and design various pro-drugs, toxic small molecules bound to a peptide that can be cleaved by one or more of the secreted proteases. Such cleavage would liberate the toxic molecule and allow it to kill prostate cancer and/or normal prostate cells that are in the proximity. Secreted by the prostate proteases are known to be inactivated in blood by various inhibitors. The above assures that pro-drug would only be specifically activated only when it is near by the prostate cells.

Our laboratory has a long-standing interest in addressing and understanding signaling events that play an important role in tumorogenesis and metastasis. In particular, we are trying to improve our understanding of androgen action, various kinase and phosphatase signaling in prostate cancer cells as well as understand stroma-epithelium interactions in normal prostate and prostate cancer.


Research Profile

  • Tombal B, Weeraratna A, Denmeade S, Isaacs J. Thapsigargin induces a calmodulin/calcineurin-dependent apoptotic cascade responsible for the death of prostatic cancer cells. The Prostate 43:303-317, 2000.
  • Gao J, Arnold JT, Isaacs JT. Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells. Cancer Res 61:5038-5044, 2001.
  • Jakobsen CM, Denmeade Sr, Isaacs JT, Gady A, Olsen CE, Christensen SB. Design, synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis to prostatic cancer cells. J Med Chem 44:4696-4703, 2001.
  • Pinski J, Parikh A, Bova GS, Isaacs JT. Therapeutic implications of enhances G(0)/G(1) checkpoint control induced by coculture of prostate cancer cells with osteoblasts. Cancer Res 61:6372-6376, 2001.
  • Pinski J, Weeraratna A, Uzgare AR, Arnold JT, Denmeade SR, Isaacs JT. Trk receptor inhibition induces apoptosis of proliferating but not quiescent human osteoblasts. Cancer Res 62:986-989, 2002.
  • Tombal B, Denmeade Sr, Gillis JM, Isaacs JT. A supramicromolar elevation of intracellular free calcium ([Ca(2+)](I)) is consistently required to induce the execution phase of apoptosis. Cell Death Differ 9:561-573, 2002.
  • Denmeade SR, Isaacs JT. A History of prostate cancer treatment. Nat Rev Cancer 2:389-396, 2002.