Brooklyn, New York, United States
Please see my biosketch in Marquis "Who's Who in the World". Our current major interest is in Cancer Stem Cells (CSCs), their role in determining tumor cure/recurrence, and an assay we have developed (the Hybrid Spheroid Assay (HSA), patented and patents pending) for measurement of their numbers and sensitivity to proposed cancer treatments for individual patients. The HSA also could save onco-pharmaceutical companies $Billions by testing new agents for their effectiveness against CSCs before going to clinical trials costing $100s of millions per new drug, 85-90% of which trials fail. If the drug does not affect CSCs, the tumor will recur. We are currently seeking funding to automate this assay to (1) perform clinical trials that would enable us to optimize cancer treatments for each individual patient based on their cancer stem cell sensitivities to possible treatment agents, and (2) to reduce the cost of new anti-cancer agent development. We have also provided the first visualization of a solid tumor CSC niche (microenvironment) and are investigating cell:cell signaling within the niche. We are also testing the predictions of our models for CSC growth and differentiation. For endometrial cancer patients our HSA has correctly predicted clinical outcomes (recurrence/local control) for 100% (7/7) of our patients.
Director of Radiation Research, Associate Director of Residency Program, (2010-2016: Associate Chair of Radiation Oncology Department). Showed that the Kinetics of DNA DSB repair can predict mammalian cell radiation survival curves. Developed and patented an assay for the measurement of individual patient cancer stem cell fraction in their tumor as well as the sensitivity of these cells to proposed treatments, thereby making possible the individualization of cancer treatment for each patient. First visualized the cancer stem cell niche for a solid tumor, showed that it is affected by irradiation, and proposed the niche as an additional target for cancer therapy. Proposed (with JY Ostashevsky) the "Clustered Loop Model" of mammalian chromosome structure and demonstrated that it explains both the dynamics and statics of higher eukaryote chromosomes in vivo (unperturbed live cells), in situ (using fluorescent in situ hybridization), in nucleoids, and in solution (using viscoelastometry) as both chromatin and naked DNA.
First demonstrated (contemporaneously with Arthur Cole) the repair of DNA double-strand breaks in mammalian cells and the consequences for cell survival. This was held to be the most important discovery in 20th century radiobiology. Showed that tissue polarity (in planarians) is controlled by bio-electrophoresis of a protein produced in the brain that inhibits stem cell differentiation into brain tissue. This model also has relevance for chicken embryo development, frog limb regeneration, and possibly, human bone healing.
Sabbatical year with Prof. Bruno H. Zimm. Work on Viscoelastometry and sedimentation theory, and their use in the study of mammalian chromosome structure and DNA damage and repair.
Continued previous work and also investigated host cell reactivation of viruses as a surrogate for DNA repair in mammalian cells. Recent revisiting of this work led to explaining why Herpes virus infections can appear after radiation therapy of cancer patients, and we recommended a protocol to prevent this and protect patients AND clinical staff from incurring these infections. Acted as Resident Statistician, during the 6-month absence of CW Gilbert, to advise colleagues on statistical analysis of their data. Taught Radiobiology in the training program for certification in Medical Radiation Therapy (DMRT course).
Research on Stem Cells, showing that survival of the organism (animal) can be understood in terms of the survival of the stem cells responsible for maintaining the vital tissue, the failure of which leads to death. Demonstrated that two equations quantitatively relate stem cell survival to organismal survival. This work led to our current understanding of radiation effects on dose-limiting normal tissues (e.g., gastro-intestinal and lung) and its application in radiation oncology. This work explained The Cellular Basis of Radiation-induced Organ/Tissue Failure and Organismal Lethality. Also explained why animals age even though their stem cells are immortal.