Trosko, James E.

About

After receiving a Ph.D. in radiation genetics, Dr. Trosko did a postdoctoral fellowship at Oak Ridge National Laboratory (1963-66) under Drs. Ernest Chu, Sheldon Wolf and Richard B. Setlow in DNA damage/repair and in vitro mutagenesis. He published the first paper showing that normal human cells could repair their UV-damaged DNA [1]. He went to Michigan State University (1966) to work on the xeroderma pigmentosum (which he & Dr. James E. Cleaver first showed that cells from these patients did not repair their UV-damaged DNA [2]), Cockaynes [3] and Blooms [4] syndromes (human genetic, sun-sensitive syndromes, predisposed to either cancer or premature aging) and to work on anti-cancer drug, cisplatin, with the late Dr. Barnett Rosenberg [5]. Later, after receiving a NCI-Career Development award, he went to work at the McArdle Laboratory for Cancer Research-University of Wisconsin on chemical carcinogenesis under the late Dr.Van R. Potter, where he discovered that the tumor promoter, TPA, was not genotoxic but inhibited gap junctional intercellular communication GJIC) [6]. After returning to MSU,  Trosko’s  lab developed 4 new in vitro assays to detect non-genotoxic chemicals that had teratogenic, tumor promoting, immuno-modulatory, neuro-, cardiovascular -and reproductive- toxic effects [7-10]. He was featured on the cover of Cancer Research as one of the investigators who linked gap junctions to the carcinogenesis process.

He coined the term, “epigenetic toxicology” [11], after showing that most of the toxic chemicals in the environment (TCDD, PBB, PCB, DDT, Dieldrin, Adrin, toxaphene, pthalates, PFOA, etc.) were (a) not genotoxic and (b) could inhibit GJIC, reversibly at non-cytotoxic concentrations.[12] Also, his lab discovered that oncogenes, such as src, ras, raf, neu,[13] could stably inhibit GJIC, while tumor suppressor genes [14], as well as multiple cancer chemo-preventive agents ( green tea components, caffeic acid ethyl ester, genistein, beta-sitosterol, resveratrol, retinoids, carotinoids, kaempherol, etc.) [15-20], and even some chemotherapeutic agents ( Lovastatin ,SAHA) [21, 22], could either prevent the inhibition of GJIC by tumor promoters or increase GJIC in tumor cells, deficient in GJIC.

All this was done based on assuming the “stem cell theory of cancer”. That led his lab to search for the few stem cells that must exist in normal tissues of cancer-generating organs. Together with Dr. Chia- Cheng Chang, they discovered, in 1986, a human adult stem cell from the kidney [23]. It was based on assuming stem cells had no functional gap junctions. Later, they discovered human breast epithelial stem cells [24, 25, 26], and other adult stem cells (pancreas, mesenchyme, liver) [27]. This led Dr. Trosko to hypothesize that the adult stem cell was the target for breast (and other cancers) and he successfully demonstrated this in his paper showing the adult human breast stem cell could be immortalized and subsequently neoplastically transformed [ 28].

In 1990-92, Dr. Trosko was Chief of Research at the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan. After returning to MSU, he demonstrated that Oct4A was a biomarker for human adult stem cells and that the human adult breast stem cell was the target cell for breast neoplastic transformation and the probable origin of the human breast “cancer stem cell”.[28] He spent a sabbatical studying human prostate stem cells and the Mediterranean diet at ARNAS-Civic Cancer Institute, Palermo, Sicily [29 ] and 6 months at Seoul National University in the Human Adult Stem Cell Laboratory , where he is continuing his studies on characterizing adult human stem cells for their potential uses in drug discovery & toxicity assessment. [30]

He plans to characterize the human “cancer stem cell” for possible specific cancer targeted chemopreventive and chemotherapy [15-22, 30] in order not to harm normal adult stem cells. Moreover, he has been the pioneer in providing a new concept to provide a mechanistic explanation of the “Barker Hypothesis”, namely that events early in embryonic/fetal/neonatal development can alter the risk to chronic diseases, such as cancer , to the individual later in life , simply by altering the quantity of adult stem cells in utero [31,32]. He has been recognized as a model teacher [ one specific example is his first graduate student’s achievement, Dr. Stephen Warren, discover of the cloned Fragile X gene] and a internationally-recognized basic science cancer researcher , in the fact that  Dr. Trosko has given over 700 lectures around the world .and research mentor by awards such as the MSU-Teacher Scholar; MSU Distinguished Professor; NCI- Career Development Awardee; Sigma Xi Senior Research Scholar; Japan Society for the Promotion of Science; Korean Ministry of Science & Technology’s “Brain Pool” Awardee; and Seoul National University “World Class University Invited Professorship”.

 

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