Benjamin L. Clarke, PhD
Biomed Sci Medical School Duluth
1035 University Dr
Duluth, MN 55812
Biomedical Sciences, Department of
Biochemistry, Molecular Biology, and Biophysics
Immunology, Center for (CFI)
Masonic Cancer Center (MCC)
PhD, University of Texas Medical Branch, 1986
My research interest is immunoendocrinology, with an emphasis on the role of neuroendocrine peptide hormones as autocrine regulators of immune function. This work is based on the effects of adrenocorticotropic hormone (ACTH) on lymphocytes. Lymphocytes produce ACTH when activated by mitogen. Lymphocytes also respond to exogenous ACTH added to in vitro cultures. However, ACTH alone does not stimulate lymphocytes, but in conjunction with a mitogen or IL2 it has a biphasic effect on lymphocyte proliferation and the secretion of immunoglobulin.
This response pattern is hypothesized to result from the opposing effects of the ACTH-induced second messengers cAMP and calcium influx. Future work will be directed toward characterizing the ACTH receptor on rat lymphocytes and determining how ACTH is capable of modulating the activation of lymphocytes by IL2.
See also: PubMed
Selected Peer Reviewed Journals:
S. Akbulut, C.A. Byersdorfer, S.L. Zimmer, C. Larsen, T.D. Humphreys and B.L. Clarke. Expression of the Melanocortin 5 Receptor on Rat Lymphocytes. Accepted by Biochemical Biophysical Research Communications, February 11, 2001.
Wermerskirchen, A.S., LaTocha, D.H. and Clarke, B.L.; "Adrenocorticotropic Hormone controls Concanavalin A activation of rat lymphocytes by modulating IL-2 production". Life Sciences 67(18), 2177-87.
Clarke, B.L.; (1999) "Binding and Processing of 125I-ACTH by Isolated rat splenic lymphocytes."Biochemical Biophysical Research Communications 266, 542-6.
Clarke, B.L., Moore, D.R., and Blalock, J.E.; (1994), "Adrenocorticotropic hormone stimulates a transient calcium uptake in rat lymphocytes." Endocrinology. 135, 1780-6.
Weigent, D.A., Clarke, B.L., and Blalock, J.E.; (1994), "Peptide design using a genetically patterned binary code: Growth hormone releasing hormone as a model." Complementary Peptides: Applications in Immunology and as Antibody Mimetics. Immunomethods 5, 91-7.
Carr, D.J.J., Woolley, T.W., and Clarke, B.L.; (1994), "The relationship between the hypotha-lamic pituitary adrenal axis and oral-induced immunosuppression." International J. Neuroscience 76, 151-64.
Clarke, B.L., Gebhardt, B.M., and Blalock, J.E.; (1993), "Mitogen-stimulated lymphocytes release biologically active corticotropin." Endocrinology 132, 983-8.
Marchase, R.B., Burkart, M.F., Rivera, A.A., Clarke, B.L., Shur, B.D., Overmeyer, G.T., and Shaw, D.R.D.; (1991), "Beta-phosphorothiolate analogues of nucleotide sugars are resistant to hydrolytic degradation and utilized efficiently by glycosyltransferases." Analytical Biochemistry 197, 40-6.
Clarke, B.L. and Bost, K.L.; (1991), "A monoclonal anti-peptide antibody mimics adrenocorticotropic hormone activity." Immunology Letters 28, 175-180.
Bost, K.L., Clarke, B.L., Xu, J., Kiyono, H., McGhee, J.R., and Pascual, D.; (1990). "Modulation of IgM secretion and H chain mRNA expression in CH12.LX.C4.5F5 B cells by adrenocorticotropic hormone."J. Immunology 145, 4326-31.
Clarke, B.L. and Blalock, J.E.; (1990), "Corticotropic activity generated by a peptide encoded from the reversed sequence of the mRNA for ACTH." Proceedings National Academy of Sciences (USA) 87, 9708-11.
Clarke, B.L. and Bost, K.L.; (1990), "A monoclonal antipeptide antibody recognizes the adreno-corticotropic receptor." Biochemical Biophysical Research Communications 168, 1020-6.
McAbee, D.D., Clarke, B.L., Oka, J.A., and Weigel, P.H.; (1990), "The activity of the same subpopulation of surface galactosyl receptors on isolated rat hepatocytes is modulated by colchicine, monensin, ATP-depletion, and chloroquine." J. Biological Chemistry 265, 629-35.
Clarke, B.L., Naylor, C., and Lennarz, W.J.; (1989), "Comparative studies on mannosylphos-phoryldolichol and glucosylphosphoryldolichol synthases." Chemistry and Physics of Lipids 51, 239-47.
Clarke, B.L. and Weigel, P.H.; (1989), "Differential effects of leupeptin, monensin and colchicine on ligand degradation mediated by the two asialoglycoprotein receptor pathways in isolated rat hepatocytes." Biochemistry J. 262, 277-84.
Clarke, B.L. and Bost, K.L.; (1989), "Differential expression of functional corticotropin (ACTH) receptors by subpopulations of lymphocytes." J. Immunology 143, 464-9.
Clarke, B.L., Oka, J.A., and Weigel, P.H; (1987), "Degradation of asialoglycoproteins mediated by the galactosyl receptor system in isolated hepatocytes: Evidence for two parallel pathways." J. Biological Chemistry 262, 17384-92.
Weigel, P.H., Clarke, B.L., and Oka, J.A; (1986), "The hepatic galactosyl receptor system: Two different ligand dissociation pathways are mediated by distinct receptor populations." Biochemistry Biophysical Research Communications 140, 43-50.
Clarke, B.L. and Weigel, P.H; (1985), "Recycling of the asialoglycoprotein receptor in isolated rat hepatocytes: ATP depletion blocks receptor recycling but not a single round of endocytosis." J. Biological Chemistry 260, 128-33.
Review Articles (Invited):
Clarke, B.L.; (1995), "Calcium Uptake by Corticotropin-Stimulated Lymphocytes: What is the Physiological Significance?" Advances in Neuroimmunology 5, 271-8.
Clarke, B.L. and Blalock, J.E.; (1991), "Characteristics of peptides specified by antisense nucleic acids." In: Applications of Antisense Nucleic Acids (A.R. vander Krol and J.N.M. Mol, eds.), Marcel Dekker, New York, pp. 169-85.
Manuscripts in Preparation:
Latocha, D.A. and Clarke, B.L. Chronic ethanol exposure to Jurkat Lymphocytes induces a mitogenic sensitivity to Concanavalin A.
Zimmer, S. Byersorfer, C., and Clarke, B.L. Expression of the MCR-5 receptor in HeLa cells: Evidence for the role of the carboxyl terminus in signal transduction and ligand internalization.
Latocha, D.H. and Clarke, B.L. Inhibition of the Concanavalin A activation of rat splenic lymphocytes is blocked by verapamil (+).
Akbulut, S. and Clarke, B.L. Adrenocorticotropic hormone stimulates the coupling of the Melanocortin 5 receptor with JAK2 in rat lymphocytes.
Gillespie, M.A., Zimmer, S.L., Humphreys, T.D., LaTocha, D.H. and Clarke, B.L. Evidence for an intracellular and cell surface pool of functional Melanocortin receptors in rat lymphocytes.
Zimmer, S.L. and Clarke, B.L. ACTH increases the binding of AP1 to the promoter region of the IL-2 gene in activated rat lymphocytes.
J.G. Drewett, S.L. Zimmer, and B.L. Clarke. (2000), "Expression of melanocortin-5 receptor reveals agonist-stimulated human aldosteronogenesis". FASEB J. 14:A1354.
Zimmer, S.L., LaTocha, D.A. and Clarke B.L. (2000), "Adrenocorticotropic hormone modulation of Lymphocyte Activation is mediated by a Verapamil(+) isomer sensitive mechanism". FASEB J. 14(6):A1180.
Akbulut, S., Zimmer, S.L. and Clarke, B.L. (2000). "Adrenocorticotropic Hormone stimulates the JAK/STAT pathway in isolated rat splenic lymphocytes". FASEB J. 14(6):A1085.
M.M. Cannedy-Clarke, Smith, R.J. and Clarke, B.L.; (1999), Development of a Bridges Program targeted to a small Population. NIH-Bridges Directors Meeting.
M.A. Gillispie and Clarke, B.L.; (1998), "Adrenocorticotropic Hormone inhibits Concanavalin A induced Apoptosis in Rat Splenic Lymphocytes: A cell cycle analysis." Molecular Biology Cell 9, 486.
Zimmer, S.L. and Clarke B.L.; (1998), "Expression of the Melanocortin MC5 receptor (MCR5) in HeLa cells: The role of the C-tail vicinyl cystinyl groups in signal transduction." Molecular Biology Cell 9, 217.
Gillespie, M.A., Freed, A., and Clarke, B.L.; (1997), "Adrenocorticotropic Hormone rescues Concanavalin A treated Lymphocytes from Apoptosis." Molecular Biology Cell 8, 149.
Byersdorfer, C. and Clarke B.L.; (1996), "Identification of the MC5 Receptor on Rat Splenocytes."Molecular Biology Cell 7, 430.
Latocha, D.H. and Clarke, B.L.; (1996), "The effects of Verapamil Sterioisomeres on Concanavalin A stimulated Calcium Uptake in isolated Rat Splenocytes." SACNAS Conference.
Clarke, B.L., Moore, D.R., and Blalock, J.E.; (1993), "Calcium uptake by adrenocorticotropin-stimulated rat lymphocytes requires channel activity and membrane fluidity." Molecular Biology Cell 4, 132.
Hageman, G.R., Simor, T., Jarpe, M., Clarke, B.L., and Blalock, J.E.; (1993), "Effects of a peptide mimetic of calcium upon the neural regulation of sinus rate and atrial contractile force." 32nd International Congress of Physiological Sciences, Glasgow, Scotland.
Clarke, B.L. and Blalock, J.E.; (1992), "Corticotropin stimulates a calcium influx that regulates rat lymphocyte cAMP and cGMP levels." Molecular Biology Cell 3, 240.
Clarke, B.L., Lyons, P.D., Carr, D.J.J., and Blalock, J.E.; (1991), "Corticotropin-induced nucleotide cyclase activity in isolated rat lymphocytes." J. Cell Biology 115, 18.
Clarke, B.L., Blalock, J.E., and Gebhardt, B.M.; (1991) "Mitogen-stimulated lymphocytes secrete biologically active corticotropin in a coculture system." FASEB J. 5, A1486.
Clarke, B.L., Swords, B.H., Blalock, J.E., and LeBoeuf, R.D.; (1990), "Antisense oligonucleotides block expression of arginine vasopressin and adrenocorticotropic hormone receptors." J. Cell Biology 111, 331.
Clarke, B.L. and Bost, K.L.; (1989) "Adrenocorticotropic hormone stimulates protein phosphorylation in isolated rat lymphocytes." J. Cell Biology 109, 218.
Clarke, B.L. and Bost, K.L.; (1989), "A monoclonal anti-peptide antibody recognizes the ACTH receptor on rat adrenal cells." FASEB J. 3, A853.
McAbee, D.D., Oka, J.A., Clarke, B.L., Lear, M.L., and Weigel, P.H.; (1989), "Redistribution and inactivation/reactivation of a subset of rat hepatic galactosyl receptors are uncoupled and differentially affected by various inhibitors." J. Cell Biology 107, 810.
Burkart, M.F., Clarke, B.L., Shur, B.D., Shaw, D.R.D., and Marchase R.B.; (1989), "Beta phosphoro-thioate analogues of nucleotide sugars are resistant to hydrolytic degradation but utilized efficiently by glycosyltransferases." J. Cell Biology 107, 191.
Gottlieb, R.A., Knowles, R.D., Clarke, B.L., Lachman, L.B., Dinarello, C.A., Lennarz, W.J., and Kleinerman, E.S.; (1988), "A heptadecapeptide homologous to retroviral envelope proteins blocks the action of interleukin-1." Proc. AACR 29, 371.
Clarke, B.L. and Lennarz, W.J.; (1987), "Topology of mannosyl- and glucosylphosphoryl-dolichol synthases in sealed microsomes from chicken oviduct." J. Cell Biology 105, 78.
Weigel, P.H., Clarke, B.L., and Oka, J.A.; (1986), "Endocytosis and ligand dissociation and degradation mediated by the hepatic galactosyl receptor occur via two different pathways." Federation Proceedings 45, 1910.
Clarke, B.L. and Weigel, P.H.; (1985), "Asialoglycoprotein receptors can mediate protein degradation by two different pathways in isolated rat hepatocytes." J. Cell Biology 101, 418.
Weigel, P.H., Clarke, B.L. and Oka, J.A.; (1984), "Surface and intracellular galactosyl receptor activity is reversibly decreased by metabolic energy poisons." J. Cell Biology 99, 372.
Oka, J.A., Clarke, B.L., and Weigel, P.H.; (1983), "The internal pool of slowly dissociating receptor asialoglycoprotein complexes return to the cell surface prior to dissociating." J. Cell Biology 97, 428.
Clarke, B.L. and Weigel, P.H.; (1982), "Effects of metabolic energy poisons on endocytosis mediated by the asialoglycoprotein receptor." J. Cell Biology 95, 442.
2000-present Associate Professor
1994-present Graduate Faculty
1995-present Member of the Immunology Center University of Minnesota
1997-present Graduate Faculty
1999-present Member of the Cancer Center, University of Minnesota