Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

PRINCIPAL INVESTIGATOR OF RESEARCH GRANTS (since 2003)
2011- Novel Substrates Of The Tcr Kinase (NIGMS) (Co-PI)
2010- Hormonal Imprinting Predetermines Developmental Expression Of Cytochrome P450s (NICHHD)
1992- 2005 Endogenous Regulators of Drug Metabolism (NIGMS)

The research proposes to unravel mechanisms regulating the ontogenesis of cytochrome P450-drug metabolism by examining hormonal imprinting of the differentiating enzyme system and the ontogenesis of the signal transduction pathways regulating expression of adult P450 isoforms. Developmental disruption of the endocrine system or signaling pathways, both common drug targets, could result in permanent alterations in drug metabolism and should be considered in formulating drug therapies for children. Lastly, we propose to identify the origins of sex differences in drug metabolism, essential in understanding the sex-based biodisposition of drugs.

Selected Publications

Sharma, M.R. Dworakowski, W. Shapiro, B.H.: Intrasplenic transplantation of isolated adult rat hepatocytes: sex-reversal and/or suppression of the major constituent isoforms of cytochrome P450. Toxicologic Pathology 40(1): 83-92, 2012.

Thangavel, C. Boopathi, E. Shapiro, B.H.: Intrinsic sexually dimorphic expression of the principal human CYP3A4 correlated with suboptimal activation of GH/glucocorticoid-dependent transcriptional pathways in men. Endocrinology 152(12): 4813-24, Dec 2011.

Thangavel, C. Shapiro, B.H.: Inherent sexually dimorphic expression of hepatic CYP2C12 correlated with repressed activation of growth hormone-regulated signal transduction in male rats. Drug Metabolism & Disposition 36(9): 1884-95, Sep 2008.

Dhir, R.N. Thangavel, C. Shapiro, B.H.: Attenuated expression of episodic growth hormone-induced CYP2C11 in female rats associated with suboptimal activation of the Jak2/Stat5B and other modulating signaling pathways. Drug Metabolism & Disposition 35(11): 2102-10, Nov 2007.

Thangavel, C. Dhir, R.N. Volgin, D.V. Shapiro, B.H.: Sex-dependent expression of CYP2C11 in spleen, thymus and bone marrow regulated by growth hormone. Biochemical Pharmacology 74(10): 1476-84, Nov 15 2007.

Thangavel, C. Shapiro, B.H.: A molecular basis for the sexually dimorphic response to growth hormone. Endocrinology 148(6): 2894-903, Jun 2007.

Verma, A.S. Shapiro, B.H.: Sex-dependent expression of seven housekeeping genes in rat liver. Journal of Gastroenterology & Hepatology 21(6): 1004-8, Jun 2006.

Thangavel, C. Dworakowski, W. Shapiro, B.H.: Inducibility of male-specific isoforms of cytochrome p450 by sex-dependent growth hormone profiles in hepatocyte cultures from male but not female rats. Drug Metabolism & Disposition 34(3): 410-9, Mar 2006.

Dhir, R.N. Dworakowski, W. Thangavel, C. Shapiro, B.H.: Sexually dimorphic regulation of hepatic isoforms of human cytochrome p450 by growth hormone. Journal of Pharmacology & Experimental Therapeutics 316(1): 87-94, Jan 2006.

Waxman, D J. Pampori, N A. Ram, P A. Agrawal, A K. Shapiro, B H.: Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450. Proceedings of the National Academy of Sciences of the United States of America 88(15): 6868-72, Aug 1 1991.

Pampori, N A. Shapiro, B H.: Sexual dimorphism in avian hepatic monooxygenases. Biochemical Pharmacology 46(5): 885-90, Sep 1 1993.

Shapiro, B H. Pampori, N A. Ram, P A. Waxman, D J.: Irreversible suppression of growth hormone-dependent cytochrome P450 2C11 in adult rats neonatally treated with monosodium glutamate. Journal of Pharmacology & Experimental Therapeutics 265(2): 979-84, May 1993.

Pampori, N A. Shapiro, B H.: Over-expression of CYP2C11, the major male-specific form of hepatic cytochrome P450, in the presence of nominal pulses of circulating growth hormone in adult male rats neonatally exposed to low levels of monosodium glutamate. Journal of Pharmacology & Experimental Therapeutics 271(2): 1067-73, Nov 1994.

Pampori, N A. Shapiro, B H.: Testicular regulation of sexual dimorphisms in the ultradian profiles of circulating growth hormone in the chicken. European Journal of Endocrinology 131(3): 313-8, Sep 1994.

Shapiro, B H. Pampori, N A. Lapenson, D P. Waxman, D J.: Growth hormone-dependent and -independent sexually dimorphic regulation of phenobarbital-induced hepatic cytochromes P450 2B1 and 2B2. Archives of Biochemistry & Biophysics 312(1): 234-9, Jul 1994.

Pampori, N A. Shapiro, B H.: Subnormal concentrations in the feminine profile of circulating growth hormone enhance expression of female-specific CYP2C12. Biochemical Pharmacology 47(11): 1999-2004, Jun 1 1994.

Pampori, N A. Shapiro, B H.: Effects of neonatally administered monosodium glutamate on the sexually dimorphic profiles of circulating growth hormone regulating murine hepatic monooxygenases. Biochemical Pharmacology 47(7): 1221-9, Mar 29 1994.

Waxman, D J. Ram, P A. Pampori, N A. Shapiro, B H.: Growth hormone regulation of male-specific rat liver P450s 2A2 and 3A2: induction by intermittent growth hormone pulses in male but not female rats rendered growth hormone deficient by neonatal monosodium glutamate. Molecular Pharmacology 48(5): 790-7, Nov 1995.

Pampori, N A. Pampori, M K. Shapiro, B H.: Dilution of the chemiluminescence reagents reduces the background noise on western blots. Biotechniques 18(4): 588-90, Apr 1995.

Agrawal, A K. Pampori, N A. Shapiro, B H.: Thin-layer chromatographic separation of regioselective and stereospecific androgen metabolites. Analytical Biochemistry 224(1): 455-7, Jan 1 1995.

Agrawal, A K. Pampori, N A. Shapiro, B H.: Neonatal phenobarbital-induced defects in age- and sex-specific growth hormone profiles regulating monooxygenases. American Journal of Physiology 268(3 Pt 1): E439-45, Mar 1995.

Agrawal, A K. Shapiro, B H.: Imprinted overinduction of hepatic CYP2B1 and 2B2 in adult rats neonatally exposed to phenobarbital. Journal of Pharmacology & Experimental Therapeutics 279(2): 991-9, Nov 1996.

Pampori, N A. Shapiro, B H.: Feminization of hepatic cytochrome P450s by nominal levels of growth hormone in the feminine plasma profile. Molecular Pharmacology 50(5): 1148-56, Nov 1996.

Agrawal, A K. Shapiro, B H.: Phenobarbital induction of hepatic CYP2B1 and CYP2B2: pretranscriptional and post-transcriptional effects of gender, adult age, and phenobarbital dose.[Erratum appears in Mol Pharmacol 1996 Jun;49(6):1142] Molecular Pharmacology 49(3): 523-31, Mar 1996.

Agrawal, A K. Shapiro, B H.: Gender, age and dose effects of neonatally administered aspartate on the sexually dimorphic plasma growth hormone profiles regulating expression of the rat sex-dependent hepatic CYP isoforms. Drug Metabolism & Disposition 25(11): 1249-56, Nov 1997.

Sharma, M C. Agrawal, A K. Sharma, M R. Shapiro, B H.: Interactions of gender, growth hormone, and phenobarbital induction on murine Cyp2b expression. Biochemical Pharmacology 56(9): 1251-8, Nov 1 1998.

Pampori, N A. Shapiro, B H.: Gender differences in the responsiveness of the sex-dependent isoforms of hepatic P450 to the feminine plasma growth hormone profile. Endocrinology 140(3): 1245-54, Mar 1999.

Pampori, N A. Shapiro, B H.: Nominal growth hormone pulses in otherwise normal masculine plasma profiles induce intron retention of overexpressed hepatic CYP2C11 with associated nuclear splicing deficiency. Endocrinology 141(11): 4100-6, Nov 2000.

Agrawal, A K. Shapiro, B H.: Latent overexpression of hepatic CYP2C7 in adult male and female rats neonatally exposed to phenobarbital: a developmental profile of gender-dependent P450s. Journal of Pharmacology & Experimental Therapeutics 293(3): 1027-33, Jun 2000.

Agrawal, A K. Shapiro, B H.: Differential expression of gender-dependent hepatic isoforms of cytochrome P-450 by pulse signals in the circulating masculine episodic growth hormone profile of the rat. Journal of Pharmacology & Experimental Therapeutics 292(1): 228-37, Jan 2000.

Agrawal, A K. Shapiro, B H.: Intrinsic signals in the sexually dimorphic circulating growth hormone profiles of the rat. Molecular & Cellular Endocrinology 173(1-2): 167-81, Feb 28 2001.

Garcia, M C. Thangavel, C. Shapiro, B H.: Epidermal growth factor regulation of female-dependent CYP2A1 and CYP2C12 in primary rat hepatocyte culture. Drug Metabolism & Disposition 29(2): 111-20, Feb 2001.

Pampori, N A. Agrawal, A K. Shapiro, B H.: Infusion of gender-dependent plasma growth hormone profiles into intact rats: effects of subcutaneous, intraperitoneal, and intravenous routes of rat and human growth hormone on endogenous circulating growth hormone profiles and expression of sexually dimorphic hepatic cyp isoforms. Drug Metabolism & Disposition 29(1): 8-16, Jan 2001.

Kaufhold, A. Nigam, P.K. Dhir, R.N. Shapiro, B.H.: Prevention of latently expressed CYP2C11, CYP3A2, and growth hormone defects in neonatally monosodium glutamate-treated male rats by the N-methyl-D-aspartate receptor antagonist dizocilpine maleate. Journal of Pharmacology & Experimental Therapeutics 302(2): 490-6, Aug 2002.

Dhir, R.N. Dworakowski, W. Shapiro, B.H.: Middle-age alterations in the sexually dimorphic plasma growth hormone profiles: involvement of growth hormone-releasing factor and effects on cytochrome p450 expression. Drug Metabolism & Disposition 30(2): 141-7, Feb 2002.

Dhir, R.N. Shapiro, B.H.: Interpulse growth hormone secretion in the episodic plasma profile causes the sex reversal of cytochrome P450s in senescent male rats. Proceedings of the National Academy of Sciences of the United States of America 100(25): 15224-8, Dec 9 2003.

Sharma, M.R. Periandythevar, P. Shapiro, B.H.: Spurious observation of splenic cyp2b1 expression. Drug Metabolism & Disposition 31(9): 1074-6, Sep 2003.

Agrawal, A.K. Shapiro, B.H.: Phenobarbital-imprinted overinduction of adult constituent CYP isoforms. Pharmacology 68(4): 204-15, Aug 2003.

Agrawal, A.K. Shapiro, B.H.: Constitutive and inducible hepatic cytochrome P450 isoforms in senescent male and female rats and response to low-dose phenobarbital. Drug Metabolism & Disposition 31(5): 612-9, May 2003.

Thangavel, C. Garcia, M.C. Shapiro, B.H.: Intrinsic sex differences determine expression of growth hormone-regulated female cytochrome P450s. Molecular & Cellular Endocrinology 220(1-2): 31-9, May 31 2004.

Verma, A.S. Dhir, R.N. Shapiro, B.H.: Inadequacy of the Janus kinase 2/signal transducer and activator of transcription signal transduction pathway to mediate episodic growth hormone-dependent regulation of hepatic CYP2C11. Molecular Pharmacology 67(3): 891-901, Mar 2005.

Agrawal, A.K. Shapiro, B.H.: Neonatal phenobarbital imprints overexpression of cytochromes P450 with associated increase in tumorigenesis and reduced life span. FASEB Journal 19(3): 470-2, Mar 2005.