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John T. Isaacs
Department Affiliation: Primary: Oncology; Secondary: Urology; Chemical and Biomolecular Engineering, The Whiting School of Engineering
Degree: Ph.D., Emory University
Telephone Number: 443-287-0553
Fax Number: 410-614-8397
E-mail address: firstname.lastname@example.org
Johns Hopkins Hospital Address: Bunting-Blaustein CRB1, Room 1M44, 1650 Orleans Street, Baltimore, MD 21231
Anti-cancer drug development; Normal and malignant stem cell biology
While there has been an explosion of knowledge about human carcinogenesis over the last 2 decades, unfortunately, this has not translated into the development of effective therapies for either preventing or treating the common human cancers. The goal of the Isaacs’ lab is to change this situation by translating theory into therapy for solid malignancies, particularly Prostate cancer. Presently, a series of drugs discovered in the Isaacs’ lab are undergoing clinical trials in patients with metastatic cancer. The ongoing drug discovery in the lab continues to focus upon developing agents to eliminate the cancer initiating stem cells within metastatic sites of cancer. To do this, a variety of bacterial and natural product toxins are being chemically modified to produce “prodrugs” whose cytotoxicity is selectively activated by proteases produced in high levels only by cancer cells or tumor associated blood vessel cells. In this way, these prodrugs can be given systemically to metastatic patients without un-acceptable toxicity to the host while being selectively activated to potent killing molecules within metastatic sites of cancer. Such a “Trojan Horse” approach is also being developed using allogeneic bone marrow derived Mesenchymal Stem cells which are genetically engineered to secrete “prodrugs” so that when they are infused into the patient, they selectively “home” to sites of cancers where the appropriate enzymatic activity is present to liberate the killing toxin sterilizing the cancer “neighborhood”.
- Denmeade, S.R., Isaacs, J.T. The SERCA pump as a therapeutic target: Making a “Smart Bomb” for prostate cancer. Cancer Biol Ther (4) 14-22, 2005. Pub Med Publication
Williams, S.A., Merchant, R.F., Garrett-Mayer, E., Isaacs, J.T., Buckley, J.T., Denmeade, S.R. A prostate-specificantigen-activated channel-forming toxin as therapy for prostatic disease. J Natl Cancer Inst. 99: 376-385, 2007. Pub Med Reference
Singh, P., Hallur, G., Anchoori, R.K., Bakare, O., Kageyama, Y., Khan, S.R., Isaacs, J.T. Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer. Prostate 68:1570-1581, 2008. Pub Med Reference
Vander Griend, D.J., Karthaus, W.L., Dalrymple, S., Meeker, A., DeMarzo, A.M., Isaacs, J.T. The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells. Cancer Res. 68:9703-9711, 2008. Pub Med Reference
Vander Griend, D.J., Antony, L., Dalrymple, S.L., Xu, Y., Christensen, S.B., Denmeade, S.R., Isaacs, J.T. Amino-acid containing thapsigargin analogs deplete androgen receptor protein via synthesis inhibition and induces the death of prostate cancer cells. Molecular Cancer Therapeutic 8:1340-1349, 2009. Pub Med Reference
- Isaacs, J.T. The long and winding road for the development of tasquinimod as an oral second- generation quinoline-3-carboxamide antiangiogenic drug for the treatment of prostate cancer. Expert Opin Investig Drugs 19:1235-1243, 2010. Pub Med Reference
Denmeade, S.R., Isaacs, J.T. Bipolar androgen therapy: The rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer. Prostate 70:1600-1607, 2010. Pub Med Reference
Other graduate programs in which Dr. Isaacs participates: