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John T. Isaacs, Ph.D.

Photo of Dr. John T. Isaacs, Ph.D.

Co-director, Pharmacology and Drug Development Program

Professor of Oncology

Expertise: Benign Prostatic Hyperplasia

Research Interests: Normal and malignant stem cell biology; Anti-cancer drug development; Prostate cancer drug development; Molecular biology of prostate cancer ...read more

Contact for Research Inquiries

Bunting-Blaustein CRB1
1650 Orleans Street
Baltimore, MD 21231 map
Phone: 443-287-0553
Fax: 410-614-8397

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Background

Dr. John T. Isaacs is a professor of urology and oncology at the Johns Hopkins School of Medicine, as well as professor of chemical and biomolecular engineering at Johns Hopkins.

Dr. Isaacs' research focuses on the development of therapies, specifically drug therapies, for the treatment of prostate and breast cancers. His goal is to translate recent advances in theoretical knowledge regarding human carcinogenesis into therapy for solid malignancies.

He completed his undergraduate degree in natural sciences at the Johns Hopkins University and received his Ph.D. in biochemistry from the Emory University School of Medicine in Atlanta, GA. After completing a postdoctoral fellowship in pharmacology and experimental therapeutics at the Johns Hopkins School of Medicine, he joined the Johns Hopkins faculty in 1980 as an assistant professor of oncology and urology. He became an associate professor in 1986, and, in 1993, accepted the designation of professor.

Dr. Isaacs has authored or co-authored over 250 published articles, has been an invited speaker or keynote presenter at more than two dozen international conferences and has received several awards for his research. He is the Editor-in-Chief of The Prostate. Dr. Isaacs is a member of several professional organizations including the American Association for Cancer Research, the American Urological Society and the European Society for Urological Oncology and Endocrinology, and has served on numerous professional committees.

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Titles

  • Co-director, Pharmacology and Drug Development Program
  • Co-director, Urologic Oncology Program
  • Professor of Oncology
  • Professor of Urology

Education

Additional Training

The Johns Hopkins University School of Medicine, Baltimore, MD, 1980, Pharmacology and Experimental Therapeutics

Research & Publications

Research Summary

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”.

Lab

Dr. Isaacs leads two distinct labs, one through the Department of Pharmacology and Molecular Sciences and one through the graduate program in Cellular and Molecular Medicine. Both labs seek to translate recent advances in theoretical knowledge regarding human carcinogenesis into therapy for solid malignancies, particularly prostate cancer.

The Pharmacology and Molecular Sciences lab focuses on 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.

The Isaacs Cellular and Molecular Medicine lab is defining the cascade of cellular and molecular events involved in Paraneoplastic cerebellar degeneration (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.

Additionally, the laboratory has an interest in addressing and understanding signaling events that play an important role in tumorogenesis and metastasis. Thus the lab is working understand androgen action, various kinase and phosphatase signaling in prostate cancer cells as well as stroma-epithelium interactions in normal prostate and prostate cancer.

Selected Publications

View all on Pubmed

Antony L, van der Schoor F, Dalrymple SL, Isaacs JT. Androgen receptor (AR) suppresses normal human prostate epithelial cell proliferation via AR/β-catenin/TCF-4 complex inhibition of c-MYC transcription. Prostate. 2014 Aug;74(11):1118-31. doi: 10.1002/pros.22828. Epub 2014 Jun 9. PMID: 24913829 [PubMed - in process]

Doan NT, Paulsen ES, Sehgal P, Møller JV, Nissen P, Denmeade SR, Isaacs JT, Dionne CA, Christensen SB. Targeting thapsigargin towards tumors. Steroids. 2014 Jul 24. pii: S0039-128X(14)00179-2. doi: 10.1016/j.steroids.2014.07.009. [Epub ahead of print] PMID: 25065587

Brennen WN, Rosen DM, Chaux A, Netto GJ, Isaacs JT, Denmeade SR. Pharmacokinetics and toxicology of a fibroblast activation protein (FAP)-activated prodrug in murine xenograft models of human cancer. Prostate. 2014 Jul 22. doi: 10.1002/pros.22847. [Epub ahead of print] PMID: 25053236

Brennen WN, Drake CG, Isaacs JT. Enhancement of the T-cell armamentarium as a cell-based therapy for prostate cancer. Cancer Res. 2014 Jul 1;74(13):3390-5. doi: 10.1158/0008-5472.CAN-14-0249. Epub 2014 Apr 18. PMID: 24747912

Regter S, Hedayati M, Zhang Y, Zhou H, Dalrymple S, Koch CJ, Isaacs JT, DeWeese TL. Androgen withdrawal fails to induce detectable tissue hypoxia in the rat prostate. Prostate. 2014 Jun;74(8):805-10. doi: 10.1002/pros.22803. Epub 2014 Mar 27. PMID: 24677180

Academic Affiliations & Courses

Graduate Program Affiliation

Pharmacology and Molecular Sciences

Cellular and Molecular Medicine

Activities & Honors

Honors

  • 4th Annual Research Award, Foundation for the Cure of Prostate Cancer (CapCure), 1996
  • 3rd Annual Research Award, Foundation for the Cure of Prostate Cancer (CapCure), 1995
  • 2nd Annual Research Award, Foundation for the Cure of Prostate Cancer (CapCure), 1994
  • 1st Annual Research Award, Foundation for the Cure of Prostate Cancer (CapCure), 1993
  • Sigma Xi Award for the best research by an Emory Graduate Student, Emory University, 1976 - 1977

Memberships

  • American Association for Cancer Research
  • American Association for the Advancement of Science
  • American Society of Andrology
  • American Urological Society
  • Endocrine Society
  • European Society for Urological Oncology and Endocrinology
  • Society for Basic Urologic Research
  • Society for Experimental Biology and Medicine
  • Urological Research
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