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Research Focus

The work of Dr. Sell and his laboratory is directed at four key areas of adult stem sells in cancer and aging.

1. The role of bone marrow and tissue stem cells in repair of liver injury and as the cells of origin of liver cancer are being examined in different models of liver toxicity and carcinogenesis in rats and mice. Different injury and carcinogenesis models induce different patterns of cellular response indicating that cells at different stages of stem cell to hepatocyte differentiation may give rise to liver cancer. The possibility that bone marrow stem cells may be cells of origin of liver cancer is being tested using bone marrow transplantation.
2. The hypothesis that aging is determined by the number or properties of stem cells in the bone marrow is being tested by transplanting bone marrow cells from early aging mice to normal mice and by transplanting normal bone marrow to early aging mice.
3. The plasticity of a fetal mouse fibroblast cell line to transdifferentiate into other tissues and to be accepted across histocompatibility barriers is being tested in rat and mouse models of injury and repair. Our preliminary data indicate that the tissue niche may determine if these cells demonstrate immune privileged and differentiation into different cell types upon transplantation.
4. The mechanisms of the interplay of the major risk factors for human liver cancer were examined in mouse models of hepatocarcinogenesis and the critical role of glutationine-s-transferase in metabolism of aflatoxin was identified as the most important factor for susceptibility to aflatoxin carcinogenesis. We are now deriving a GST knockout mouse line to examine further this critical pathway.
5. Finally the contribution of bone marrow stem cells to breast cancer is being tested using transplantation of bone marrow from male donors with strong oncogenes under the control of breast specific promoters to normal female mice.

Ongoing Research

• Cancer: To determine if bone marrow derived mesenchymal stem cells influence the development of cancers in other tissues.
• Cancer: To block proliferation of breast cancer stem cells by small molecular inhibitors or inhibitory RNA. This is a critical step to preventing re-growth of breast cancer after chemotherapy or radiation therapy.
• Carcinogenesis: To study the metabolism of aflatoxin and development of liver cancer in mice lacking glutathionine-S-transferase.
• Aging: To compare the ability of young vs. old bone marrow derived stem cells to reconstitute and provide long term survival after lethal irradiation and transplantation, and the ability of wild-type bone marrow to prolong life of early aging mice.

Honors and Awards

• Listed in Current Contents as one of 1,000 most quoted scientists, 1981
• Paper listed as “Citation Classic” by Current Contents, 1984
• Philip S. Hench Distinguished Alumnus Award, U. Pittsburgh School of Medicine, 1988
• Distinguished Scientist Award, International Academy of Tumor Marker Oncology, 1998
• Gary J. Miller Memorial Award for excellence in teaching, AACR, 2002
• Rudolph L. K. Virchow Award, LeadershipMedica, ITALY, 2005
• Legacy Laureate, University of Pittsburgh (Highest Honor for Alumni), 2005.
• Paper cited as Scientific Landmark in Cancer Research by the American Association for Cancer Research, 2007
• Abbott Award of the International Society for Oncodevelopmental biology and Medicine, 2007
• Keynote Speaker, International Academy of Pathology, Athens, Greece, 2008

Selected Publications

• Sell, S. and Gell, P.G.H. Studies on rabbit lymphocytes in vitro. I. Stimulation of blast transformation with an antiallotype serum. J. Exp. Med. 122:423-441, 1965.

A CURRENT CONTENTS CITATION CLASSIC

• Sell, S. and Pierce, G.B. Biology of Disease: Maturation arrest of stem cell differentiation is a common pathway for the cellular orgin of teratocarcinomas and epithelial cancers. Lab. Invest. 70:6-21, 1994. AN AACR SCIENTIFIC LANDMARK
• Sell, S. Stem cell origin of cancer and differentiation therapy. Crit. Rev. Oncology and Hematology, 52:1-28, 2004.
• Crawford, DR, Ostrowski, S., Vakharia, D., Ilic, Z., Sell, S. Separate evolution of hepatitis B virus negative foci and hepatocellular carinomas in transgenic HBsAg (_alb/psx_) mice. Am. J. Pathology, 169:223-232, 2006.
• Sell S. Potential gene therapy for cancer stem cells. Current Gene Therapy. 6:579-591, 2006.
• Sell S. Cancer and Stem Cell Signaling: A Guide to Preventive and Therapeutic Strategies for Cancer Stem Cells. Stem Cell Reviews, 3:1-6, 2007.
• Sell S., Leffert HL. Liver Cancer Stem Cells. J. Clin. Oncology. 26:2800-2805, 2008
• Sell, S. alpha-fetoprotein, Stem Cells, and Cancer. The Abbot Award Lecture. Tumor Biology, 29:161-180, 2008.