Biomedical Research Education & Training
Faculty Member

Russell, William E., M.D.
Professor of Pediatrics
Cornelius Vanderbilt Chair
Professor of Cell and Developmental Biology

Lab Url: N/A

Phone Number: 615-936-1874

Email Address: bill.russell@vanderbilt.edu

Russell, William's picture
Academic history
B.S., University of Michigan, Ann Arbor, MI
M.D., Harvard Medical School, Boston, MA
, Massachusetts Gen. Hospital, Boston, MA
, Massachusetts Gen. Hospital, Boston, MA
, University of North Carolina, Chapel Hill, NC

Office Address   Mailing Address

7710 MRBIV

11136 DOT 9170


Research Keywords
Liver Regeneration; ErbB Receptors; Guanylyl Cyclase; Plasminogen Activator System

Patient Care Specialty
Pediatric Endocrinology

Research Description
The principal focus of the laboratory is to define the mechansims, both stimulatory and inhibitory, that control the regeneration of liver. The regenerating liver is used as a model in which to study the cellular and molecular mechanisms of growth control in a normal, non-neoplastic tissue. The critical issues to be understood in the process are: which signals sense the acute loss of liver mass and initiate regenerative growth; which signals maintain the differentiated functions of the liver during proliferation, and which signals stop liver growth when it has reached its appropriate mass? We aim to identify the major signals that regulate regeneration, the cells and tissues in which they are generated, and the nature of the cellular and molecular cross-talk that controls them. We study these problems in whole animals, some genetically modified to overexpress or block critical regulatory molecules, and others treated with growth factors or neutralizing antibodies; in primary cultures and lines of hepatocytes and other liver-derived cells; and in subcellular fractions of cells.


A major focus in the lab is the role of EGF-like molecules in liver growth and metabolism.


Although a potent hepatic mitogen, EGF was reported long ago to have actions that both mimic and antagonize those of insulin in the liver. The EGF receptor (EGFr) is one of a family of four related tyrosine kinase receptors: EGFr, ErbB2, ErbB3, and ErbB4. Ligands of these receptors induce hetero- and homodimers and divergent downstream signaling. Adult liver expresses only EGFr and ErbB3, while fetal liver expresses EGFr, ErbB2 and ErbB3. Ligands of both the EGFr (TGFalpha, amphiregulin, epiregulin, betacellulin, and HB-EGF) and ErbB3 (heregulins or neuregulins) are expressed in liver or pancreas. The laboratory is actively investigating the proliferative and metabolic signals generated by this important system.


ErbB2, which can dimerize with either EGFr or ErbB3 is strongly expressed in fetal and neonatal liver, but is extinguished around the time of weaning, suggesting it to be a developmental switch. The model under investigation is that the ErbB receptor family transduces growth and metabolic signals in the liver, and perhaps in other tissues, and that the various ligands and receptors in this family have different actions at different developmental stages. In addition to developmental differences in ErbB receptor expression, there are also striking zonal and circadian differences in their expression, adding to the potential richness and subtlety of ErbB signaling in the liver.


Other areas of active investigation in the laboratory include the role of receptor guanylyl cyclases, the plasminogen activator system, and also of growth inhibitors in the development and regeneration of liver.


Clinical Interests
Endocrine disorders of children from birth through adolescence.

Publications
Rosenbloom, ST, Qi, X, Riddle, WR, Russell, WE, Donlevy, SC, Giuse, D, Sedman, AB, Spooner, SA. Implementing Pediatric Growth Charts into an Electronic Health Record System. J Am Med Inform Assoc, 2006 PMCID:1513651

Romero-Gallo, J, Sozmen, EG, Chytil, A, Russell, WE, Whitehead, R, Parks, WT, Holdren, MS, Her, MF, Gautam, S, Magnuson, M, Moses, HL, Grady, WM. Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy. Oncogene, 24(18), 3028-41, 2005

Hinkle, CL, Sunnarborg, SW, Loiselle, D, Parker, CE, Stevenson, M, Russell, WE, Lee, DC. Selective roles for tumor necrosis factor alpha-converting enzyme/ADAM17 in the shedding of the epidermal growth factor receptor ligand family: the juxtamembrane stalk determines cleavage efficiency. J Biol Chem, 279(23), 24179-88, 2004

Lee, DC, Sunnarborg, SW, Hinkle, CL, Myers, TJ, Stevenson, MY, Russell, WE, Castner, BJ, Gerhart, MJ, Paxton, RJ, Black, RA, Chang, A, Jackson, LF. TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Ann N Y Acad Sci, 995, 22-38, 2003

Carver, RS, Stevenson, MC, Scheving, LA, Russell, WE. Diverse expression of ErbB receptor proteins during rat liver development and regeneration. Gastroenterology, 123(6), 2017-27, 2002

Mathew, Revi P, Najjar, Jennifer L, Lorenz, Rodney A, Mayes, Darrel E, Russell, William E. Premature pubarche in girls is associated with functional adrenal but not ovarian hyperandrogenism. J Pediatr, 141(1), 91-8, 2002

Scheving, Lawrence A, Stevenson, Mary C, Taylormoore, Jonathan M, Traxler, Peter, Russell, William E. Integral role of the EGF receptor in HGF-mediated hepatocyte proliferation. Biochem Biophys Res Commun, 290(1), 197-203, 2002

Sunnarborg, SW, Hinkle, CL, Stevenson, M, Russell, WE, Raska, CS, Peschon, JJ, Castner, BJ, Gerhart, MJ, Paxton, RJ, Black, RA, Lee, DC. Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J Biol Chem, 277(15), 12838-45, 2002

NIH Consensus Development Panel. Osteoporosis Prevention, Diagnosis, and Therapy. JAMA, 285, 785-795, 2001

Scheving, L A, Russell, W E. Insulin and heregulin-beta1 upregulate guanylyl cyclase C expression in rat hepatocytes: reversal by phosphodiesterase-3 inhibition. Cell Signal, 13(9), 665-72, 2001

Busse D, Doughty RS, Ramsey TT, Russell WE, Price JO, Flanagan WM, Shawver LK, and Arteaga CL. Reversible G1 arrest induced by inhibition of the EGF receptor tyrosine kinase requires up-regulation of p27KIP1 independent of MAPK activity. J. Biol. Chem., 275, 6987-6995, 2000

Busse, D, Doughty, R S, Ramsey, T T, Russell, W E, Price, J O, Flanagan, W M, Shawver, L K, Arteaga, C L. Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent of MAPK activity. J Biol Chem, 275(10), 6987-95, 2000

Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J, and the Genentech, Inc., Cooperative Study Group. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: randomized, multicenter trial. J. Clin Endocrinol Metab, 85, 3653-3660, 2000

Carver RS, Russell WE. A diversity of EGF-like ligands and receptors in liver. Fleig W (ed). Normal and Malignant Liver Cell Growth-Falk Workshop Kluwer Academic Publishers, 33-46, 1999

Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, Russell WE, Castner BJ, Johnson RS, Fitzner JN, Boyce RW, Nelson N, Kozlosky CJ, Wolfson MF, Rauch CT, Cerretti DP, Paxton RJ, March CJ, Black RA. An essential role for ectodomain shedding mammalian development. Science , 282, 1281-1284, 1998

Peschon, JJ, Slack, JL, Reddy, P, Stocking, KL, Sunnarborg, SW, Lee, DC, Russell, WE, Castner, BJ, Johnson, RS, Fitzner, JN, Boyce, RW, Nelson, N, Kozlosky, CJ, Wolfson, MF, Rauch, CT, Cerretti, DP, Paxton, RJ, March, CJ, Black, RA. An essential role for ectodomain shedding in mammalian development. Science, 282(5392), 1281-4, 1998

Roselli HC, Su M, Washington K, Kerins DM, Vaughan DE, Russell WE. Liver regeneration is delayed in urokinase- deficient mice. Am J Physiol (GI and Liver Physiol 38). , 275, G1472-G1479, 1998

Roselli, H T, Su, M, Washington, K, Kerins, D M, Vaughan, D E, Russell, W E. Liver regeneration is transiently impaired in urokinase-deficient mice. Am J Physiol, 275(6 Pt 1), G1472-9, 1998

Russell WE, Carver RS. The EGF/TGF family of growth factors and their receptors. Strain AJ, andDiehl AM (eds) Liver Growth and Repair: From Basic Science to Clinical Practice. London: Chapman & Hall, Ltd., 185-218, 1998

Carver RS, Mathew PM, Russell WE. Hepatic expression of ErbB3 is repressed by insulin in a pathway sensitive to PI-3 kinase inhibitors. Endocrinology, 138, 5195-5201, 1997

Carver, R S, Mathew, P M, Russell, W E. Hepatic expression of ErbB3 is repressed by insulin in a pathway sensitive to PI-3 kinase inhibitors. Endocrinology, 138(12), 5195-201, 1997

Berkowitz EA, Seroogy KB, Schroeder JA, Russell WE, Evans EP, Riedel RF, Phillips HK, Harrison CA, Lee DC, Luetteke NC. Characterization of the mouse TGF gene: its expression during eyelid development and in waved-1 tissues. Cell Growth & Diff, 7, 1271-1282, 1996

Berkowitz, EA, Seroogy, KB, Schroeder, JA, Russell, WE, Evans, EP, Riedel, RF, Phillips, HK, Harrison, CA, Lee, DC, Luetteke, NC. Characterization of the mouse transforming growth factor alpha gene: its expression during eyelid development and in waved 1 tissues. Cell Growth Differ, 7(9), 1271-82, 1996

Carver, R S, Sliwkowski, M X, Sitaric, S, Russell, W E. Insulin regulates heregulin binding and ErbB3 expression in rat hepatocytes. J Biol Chem, 271(23), 13491-6, 1996

Carver, R. S., Sliwkowski, M. X., Sitaric, S., Russell, W. E. Insulin regulates ErbB3 and heregulin binding in rat hepatocytes. J. Biol. Chem., 271, 13491-13496, 1996

Russell, W E, Kaufmann, W K, Sitaric, S, Luetteke, N C, Lee, D C. Liver regeneration and hepatocarcinogenesis in transforming growth factor-alpha-targeted mice. Mol Carcinog, 15(3), 183-9, 1996

Russell, W. E., Kaufmann, W. K., Sitaric, S., Luetteke, N. C., Lee, D. C. Liver regeneration and hepatocarcinogenesis in TGFalpha targeted mice. Molecular , 15, 183-189, 1996

Scheving LA, Russell WE, Chong K-M. Structure, glycosylation and localization of rat intestinal heat-stable enterotoxin receptor/guanylyl cyclase C: Modulation by fasting. Am J Physiol (Gastrointest Liver Physiol 34), 271, G959-968, 1996

Scheving, L A, Russell, W E. Guanylyl cyclase C is up-regulated by nonparenchymal cells and hepatocytes in regenerating rat liver. Cancer Res, 56(22), 5186-91, 1996

Scheving, L A, Russell, W E, Chong, K M. Structure, glycosylation, and localization of rat intestinal guanylyl cyclase C: modulation by fasting. Am J Physiol, 271(6 Pt 1), G959-68, 1996

Scheving, L.A., Russell, W.E. Guanylyl cyclase C is up-regulated by nonparenchymal cells and hepatocytes in regenerating rat liver. Cancer Research , 56, 5186-5191, 1996

Barnard, J A, Beauchamp, R D, Russell, W E, Dubois, R N, Coffey, R J. Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology. Gastroenterology, 108(2), 564-80, 1995

Duddy SK, Earp HS, Russell WE, Smith GJ, Grisham JW. Differential dependence of the tumorigenicity of chemically transformed rat liver epithelial cells on autocrine production of transforming growth factor alpha. Cell Growth & Differentiation , 251-261, 1995

Duddy, SK, Earp, HS, Russell, WE, Smith, GJ, Grisham, JW. Differential dependence of the tumorigenicity of chemically transformed rat liver epithelial cells on autocrine production of transforming growth factor alpha. Cell Growth Differ, 6(3), 251-61, 1995

Russell WE, Dempsey PJ, Sitaric S, Peck AJ, Coffey Jr, RJ. Transforming growth factor- concentrations increase in regenerating rat liver: Evidence for a delayed accumulation of mature TGF-. Endocrinology , 133, 1731-1738, 1993

Russell, W E, Dempsey, P J, Sitaric, S, Peck, A J, Coffey, R J. Transforming growth factor-alpha (TGF alpha) concentrations increase in regenerating rat liver: evidence for a delayed accumulation of mature TGF alpha. Endocrinology, 133(4), 1731-8, 1993

Russell, WE. Protect your assets from future claims. CDS Rev, 86(4), 14-5, 1993

Polk, W H, Dempsey, P J, Russell, W E, Brown, P I, Beauchamp, R D, Barnard, J A, Coffey, R J. Increased production of transforming growth factor alpha following acute gastric injury. Gastroenterology, 102(5), 1467-74, 1992

Millard WJ, Romano TO, Layden MP, Russell WE, Martin RJ. Growth hormone secretion in the obese male rat: Modulation by the gonadal and thyroid axes. Growth Dev & Aging , 55, 91-103, 1991

Millard, WJ, Romano, TM, Layden, MP, Russell, WE, Martin, RJ. Growth hormone secretion in the obese male rat: modulation by the gonadal and thyroid axes. Growth Dev Aging, 55(2), 91-103, 1991

Coffey, R J, Russell, W E, Barnard, J A. Pharmacokinetics of TGF beta with emphasis on effects in liver and gut. Ann N Y Acad Sci, 593, 285-91, 1990

Cunningham, JJ, Lydon, MK, Russell, WE. Calorie and protein provision for recovery from severe burns in infants and young children. Am J Clin Nutr, 51(4), 553-7, 1990

Donaghue KC, Badger TO, Millard WJ, Frisch LS, Russell WE. Absence of ultradian rhythm or diurnal variation in insulin-like growth factor-I (IGF-I) in rats. Neuroendocrinol, 52, 1-8, 1990

Donaghue, KC, Badger, TM, Millard, WJ, Frisch, LS, Russell, WE. Absence of ultradian rhythm or diurnal variation in insulin-like growth factor-I in rats. Neuroendocrinology, 52(1), 1-8, 1990

Maiter, DM, Gabriel, SM, Koenig, JI, Russell, WE, Martin, JB. Sexual differentiation of growth hormone feedback effects on hypothalamic growth hormone-releasing hormone and somatostatin. Neuroendocrinology, 51(2), 174-80, 1990

Gabriel, SM, Millard, WJ, Koenig, JI, Badger, TM, Russell, WE, Maiter, DM, Martin, JB. Sexual and developmental differences in peptides regulating growth hormone secretion in the rat. Neuroendocrinology, 50(3), 299-307, 1989

Smith, EP, Russell, WE, French, FS, Wilson, EM. A form of basic fibroblast growth factor is secreted into the adluminal fluid of the rat coagulating gland. Prostate, 14(4), 353-65, 1989

Lin S-H, Russell WE. Two Ca2+-dependent ATPases in rat liver plasma membrane: The previously purified Ca2+(Mg2+)- ATPase is not a Ca2+-pump but an ecto-ATPase. J Biol Chem , 263, 12253-12258, 1988

Lin, SH, Russell, WE. Two Ca2+-dependent ATPases in rat liver plasma membrane. The previously purified (Ca2+-Mg2+)-ATPase is not a Ca2+-pump but an ecto-ATPase. J Biol Chem, 263(25), 12253-8, 1988

Russell WE. Transforming growth factor beta (TGF-?) inhibits hepatocyte DNA synthesis independent of EGF binding and EGF receptor phosphorylation. J Cell Physiol, 135, 253-261, 1988

Russell WE, Coffey RJ, Jr, Ouellette AJ, Moses HL. Type ? transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci USA, 85, 5126-5130, 1988

Russell, WE. Transforming growth factor beta (TGF-beta) inhibits hepatocyte DNA synthesis independently of EGF binding and EGF receptor autophosphorylation. J Cell Physiol, 135(2), 253-61, 1988

Russell, WE, Coffey, RJ, Ouellette, AJ, Moses, HL. Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci U S A, 85(14), 5126-30, 1988 PMCID:281701

Cleveland, RH, Kushner, DC, Russell, WE, Herman, TE, Kim, SH, Crawford, J. Lipoid cell tumor of the ovary: a cause of virilization in girls. Am J Dis Child, 141(7), 716-8, 1987

Coughlin, JP, Austen, WG, Donahoe, PK, Russell, WE. Liver regeneration during immunosuppression. J Pediatr Surg, 22(6), 566-70, 1987

Peters, MA, Lau, EP, Snitman, DL, Van Wyk, JJ, Underwood, LE, Russell, WE, Svoboda, ME. Expression of a biologically active analogue of somatomedin-C/insulin-like growth factor I. Gene, 35(1-2), 83-9, 1985

Russell WE, D'Ercole AJ, Underwood LE. Somatomedin C/Insulinlike growth factor-I during liver regeneration in the rat. Am J Physiol (Endocrinol Metab 11). , 248, E618-E623, 1985

Russell, WE. Growth hormone, somatomedins, and the liver. Semin Liver Dis, 5(1), 46-58, 1985

Russell, WE, D'Ercole, AJ, Underwood, LE. Somatomedin C/insulinlike growth factor I during liver regeneration in the rat. Am J Physiol, 248(5 Pt 1), E618-23, 1985

McGowan, JA, Russell, WE, Bucher, NL. Hepatocyte DNA replication: effect of nutrients and intermediary metabolites. Fed Proc, 43(1), 131-3, 1984

Russell WE, Van Wyk JJ, Pledger WJ. Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin-C. Proc Natl Acad Sci USA, 81, 2389-2392, 1984

Russell, WE, McGowan, JA, Bucher, NL. Partial characterization of a hepatocyte growth factor from rat platelets. J Cell Physiol, 119(2), 183-92, 1984

Russell, WE, McGowan, JA, Bucher, NL. Biological properties of a hepatocyte growth factor from rat platelets. J Cell Physiol, 119(2), 193-7, 1984

Russell, WE, Van Wyk, JJ, Pledger, WJ. Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci U S A, 81(8), 2389-92, 1984 PMCID:345065

Van Wyk, JJ, Russell, WE, Li, CH. Synthetic somatomedin C: comparison with natural hormone isolated from human plasma. Proc Natl Acad Sci U S A, 81(3), 740-2, 1984 PMCID:344911

Kingsnorth, AN, Russell, WE, McCann, PP, Diekema, KA, Malt, RA. Effects of alpha-difluoromethylornithine and 5-fluorouracil on the proliferation of a human colon adenocarcinoma cell line. Cancer Res, 43(9), 4035-8, 1983

Russell WE, Bucher NLR. Vasopressin modulates liver regeneration in the Brattleboro rat. Am J Physiol (Gastrointest Liver Physiol 8), 245, G321-G324, 1983

Russell, WE, Bucher, NL. Vasopressin modulates liver regeneration in the Brattleboro rat. Am J Physiol, 245(2), G321-4, 1983

McFadden, D, Jeffress, LA, Russell, WE. Individual differences in sensitivity to interaural differences in time and level. Percept Mot Skills, 37(3), 755-61, 1973

Russell, WE. Insolubilization and activation of arterial actomyosin by bivalent cations. Eur J Biochem, 33(3), 459-66, 1973


Postdoctoral Position Available
no

Postdoctoral Position Details
N/A

Updated Date
01/27/2009