Nancy L. R. Bucher, M.D.

Professor Emeritus

Contact Information:

Email: busmpath@bu.edu

Education:

1935 A.B. Bryn Mawr College, Bryn Mawr, Pennsylvania

1943 M.D., Johns Hopkins Medical School, Baltimore, Maryland

Postdoctoral Training:

Award:

Active member of American Association for the Advancement of Science, since 1986

Active member of American Academy of Arts and Sciences, since 1991

The Distinguished Scientific Achievement award from the American Liver Foundation, 2001

Accomplishments:

• Upon graduation from Johns Hopkins in 1943, she undertook an internship at Boston University School of Medicine – Boston City Hospital and participated, under the direction of Chester Keefer, MD Chief of Medicine, in a nationwide study of a new wonder drug. Dr. Bucher commented that “In administering this new medicine (penicillin), we saw a miracle every day.”
• Dr. Bucher’s contributions to the study of liver regeneration, the understanding of growth factors and the cholesterol synthesis pathway led to her being recognized, by name, in two Nobel Laureate Prize acceptance speeches. Drs. Feodor Lynen and Konrad Bloch 1964, recipients of the Nobel Prize in Physiology or Medicine.
• Dr. Bucher became an elected fellow of the American Academy of Arts and Sciences (AAAS), a nationwide honor society chartered in 1780 and dedicated to scholarship and the advancement of learning. Nancy’s prestigious appointment as a fellow in the AAAS (until recent years, a rare woman fellow). Other Fellows in the Academy include Presidents George Washington, John Adams, and Thomas Jefferson and Ben Franklin.
• Dr. Bucher successfully fan an independent laboratory at Harvard Medical School until she reached a mandatory retirement age at the age of 65. She moved to the Shiners Hospital to continue her work and mandated to retire at the age of 70. She then was recruited to the BU School of Medicine where she worked until she was 98. As an Emeritus Professor, Dr. Bucher was the oldest member of the department of Pathology & Laboratory Medicine. She passed away at the age of 103 in 2017.
• A recent article “The Aging Human Liver: The Weal and Woe of Evolutionary Legacy”, Robert K Gieseler, Thomas Schreiter, Ali Canbay Z Gastroenterol 2023; 61(01): 83-94 made a dedication as follows: “This contribution is dedicated to the memory of the one who started it all: Nancy Leslie Rutherford Bucher, M.D. (1913 – 2017”

Research Interests or Interests:

My long term research project has focused on liver regeneration and its regulation.

Cancer is a form of uncontrolled growth. We are exploring growth controls by studying readily inducible, but perfectly controlled growth in a normal organ, namely rat liver, in which liver regeneration is readily induced by partial hepatectomy. For in depth investigation we and others have found that cultures of freshly isolated hepatocytes as three-dimensional spheroids, which can realistically reflect aspects of hepatocytes functions in vivo. Synthesis is suppressed despite presence of a potent growth factor (EGF) and expression of the immediate early genes is shut off as in normal liver. These genes are activated during the cell isolation, but gain normal quiescence after a few days in the spheroids. On the contrary, if the cells are cultured as monolayers, they completely fail to exhibit any normal hepatocytes behaviors. The hepatocytes spheroids have been proposed as the cell source in a variety of diagnostic, discovery and therapeutic applications, as a bioartifical liver.

Representative Publications

• Bucher, N.L.R. and Glinos, A.D.: The effects of age on regeneration of rat liver. Cancer Res. 10:324-332, 1950.
  
• Bucher, N.L.R., Scott, J.F. and Aub, J.C.: Regeneration of the liver in parabiotic rats. Cancer Res. 11: 457-465, 1951.
  
• Bucher, N.L.R.: The formation of radioactive cholesterol and fatty acids from C14-labeled acetate by rat liver homogenates. J. Am. Chem. Soc. 75:498, 1953.
  
• Bucher, N.L.R. and McGarrahan, K.E.: The biosynthesis of cholesterol from acetate-1-C14 by cellular fractions of rat liver. J. Biol. Chem. 222:1-15, 1956.
  
• Bucher, N.L.R., Overath, P. and Lynen, F.: ß-Hydroxy ß-methyl-glutaryl coenzyme A reductase, cleavage and condensing enzymes in relation to cholesterol formation in rat liver. Biochim. Biophys. Acta 40: 491-501, 1960.
  
• Bucher, N.L.R. and Swaffield, M.N.: Rate of incorporation of (6-14C) orotic acid into uridine 5′-triphosphate and cytidine 5′-triphosphate and nuclear ribonucleic acid in regenerating rat liver. Biochim. Biophys. Acta 108: 551-567, 1965.
  
• Moolten, F.L. and Bucher, N.L.R.: Regeneration of rat liver: transfer of “humoral” agent by cross circulation. Science 158:272-274, 1967
  
• Bucher, N.L.R.: Experimental aspects of hepatic regeneration. New Engl. J. Med. 277:686-696; 738-746, 1967.
  
• Bucher, N.L.R. and Swaffield, M.N.: Regeneration of liver in rats in the absence of portal splanchnic organs and a portal blood supply. Cancer Res. 33:3189-3194, 1973.
  
• Bucher, N.L.R. and Swaffield, M.N.: Synergistic action of glucagon and insulin in relation to hepatic regeneration. In: Advances in Enzyme Regulation: George Weber (Ed.), Pergamon Press, Inc., New York, Volume 13, 1975, pp. 281-293.
  
• Bucher, N.L.R. and Swaffield, M.N.: Synergistic action of insulin and glucagon in hepatic regeneration. Lancet i:646, 197
  
• Farivar, M., Wands, J.D., Isselbacher, K.J. and Bucher, N.L.R.: Effects of insulin and glucagon on fulminant murine hepatitis. New Engl. J. Med. 295:1517-1519, 1976.
  
• Bucher, N.L.R.: Combined influences of insulin and glucagon upon hepatocytes in rats with liver loss or viral injury. In: Glucagon: Its Role in Physiology and Medicine. Foa, P.P., Bajaj, J.S. and Foa, N.L. (Eds.), Springer-Verlag, New York, 1977, pp. 393-402.
  
• McGowan, J.A., Strain, A.J. and Bucher, N.L.R.: DNA synthesis in primary cultures of adult rat hepatocytes in a defined medium: effects of epidermal growth factor, insulin, glucagon, and cyclic-AMP. J. Cell. Physiol. 108: 353-363, 1981.
  
• McGowan, J.A. and Bucher, N.L.R.: Hepatotrophic Activity of Pyruvate. In Isolation, characterization and use of hepatocytes: R.A. Harris and N.W. Cornell (Eds.) 1983. Elsevier Science Publishing Co., New York pp. 165-170.
  
• Russell, W.E., McGowan, J.A. and Bucher, N.L.R.: Biological properties of a hepatocyte growth factor from rat platelets. J. Cell Physiol. 119:193-197, 1984.
  
• McGowan, J.A., Russell, W.E. and Bucher, N.L.R.: Hepatocyte DNA replication: effect of nutrients and intermediary metabolites. Fed. Proc. 43:131-133, 1984.
  
• Ben Ze’ev, A., Robinson, G.S., Bucher, N.L.R. and Farmer, S.R.: Cell-cell and cell matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of adult rat hepatocytes. Proc. Natl. Acad. Sci (USA) 85:2161-2165, 1988.
  
• Bucher, N.L.R., Robinson, G.S. and Farmer, S.R.: Effects of extracellular matrix on hepatocyte growth and gene expression In Seminars in Liver Disease. 10:11-19, 1990.
  
• Mischoulon, D., Kotliar, N., Pilch, P.F., Bucher, N.L.R. and Farmer, S.R. Differential regulation of glucose transporter mRNAs (GLUT-1 and GLUT-2) in response to growth factors and extracellular matrix in primary cultures of rat hepatocytes, J. Cell Physiol. 153:288-296, 1992.
  
• B Rana, D Mischoulon, Y Xie, N L Bucher, and S R Farmer: Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors. Mol Cell Biol. 1994 Sep; 14(9):5858-69.
  
• Rana, B. Xie, Y., Bucher, N.L.R., and Farmer, SR. Growth-Related Changes in the Binding Activity of Hepatic Nuclear Proteins that Associate with the C/EBP Regulatory Domain within the C/EBPa Gene. J. Biol Chem. 270: 18123-181 32,1995
  
• Boyce, F.M. and Bucher, N.L.R. Baculovirus-mediated Gene Transfer into Mammalian Cells. Proc. Nat’I Acad. Sci. USA 93: 2348-2352, 1996
  
• Schadinger SE. Bucher NL. Schreiber BM. Farmer SR. PPAR2 regulates lipogensis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 288: E1195-E1205, 2005