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RICHARD R. ALMON
Molecular Physiology, Endocrinology and
Pharmacology
Professor Biological Sciences
Adjunct Professor Pharmaceutics
B.S 1968 MS 1970 Ph.D 1971,
University of Illinois
Postdoctoral work 1971 Duke University
Research Assistant Professor 1975 University of
California/San Diego
Professor Biological Sciences
Adjunct Professor Pharmaceutics, School of Pharmacy |
Address Information
Richard R. Almon
Department of Biological Sciences
107 Hochstetter Hall
State University of New York at Buffalo
Buffalo, NY 14260
(716) 645-4909
To send e-mail: almon@buffalo.edu
Course Information
Dr.
Almon's BIO 129 course
RESEARCH SUMMARY:
Close to one half of all protein in the
body is contained in the musculature. This protein mass serves
two quite different purposes. The first and most obvious function
is mechanics (movement and posture). The second, perhaps less
obvious function, is to support general body energy metabolism.
When necessary, amino acid carbon is removed from the muscle and
used for gluconeogenesis by the liver. A structurally related
group of steroid hormones, glucocorticoids, express the systemic
demand for amino acid carbon from the musculature. The central
focus of the work in this laboratory is in understanding the
mechanism by which the systemic demand for amino acid carbon is
discriminately distributed amongst the various muscles of the
body. In general, the quality and quantity of mechanical activity
regulates protein metabolism in skeletal muscle. The character of
mechanical activity also regulates many aspects of the expressed
characteristics of a muscle. By manipulating the character of
muscle mechanical activity, it is possible to change several
expressed characteristics of a muscle. These expressed
characteristics include hormonal sensitivities, isozymes of the
contractile apparatus, and enzymes involved in energy metabolism.
By manipulating the character of mechanical activity, it is also
possible to cause a muscle to atrophy or hypertrophy. The goal of
this work is to develop quantitative models that describe the
integrative regulation of muscle protein mass and gene expression
by mechanical activity and hormones. The general approach is to
use animal manipulations to induce atrophy or hypertrophy in
selected muscles within the context of controlled changes in the
systemic hormonal milieu. We then analyze at the structural ,
cellular, and molecular levels the characteristics of the
manipulated muscles. At the present time, our particular interest
is in changes in the expression of protein and message for
several receptors, myosin isozymes, and enzymes involved in
energy metabolism. Methodologies used in the laboratory include
animal surgery, cell fractionation, equilibrium binding assays,
enzyme kinetics, RIAs, HPLC, light and fluorescent
spectrophotometry, electrophoresis, and Northern Western
hybridizations, ELISA, and quantitative rtPCR.
SELECTED PROJECTS:
- Mechanical regulation of the sensitivity of muscles to
glucocorticoids, insulin and recombinant growth hormone.
- Aging skeletal muscle: disuse and recovery.
- Growing muscle: disuse and recovery
Collaborative projects with:
William Jusko, Pharmaceutics;
Marilyn Morris, Pharmaceutics;
Cathleen Boji, Pharmaceutics;
Luc Gosslin, Physical Therapy and Exercise Science.
SELECTED PUBLICATIONS:
- Yang EH, Almon RR, Dubois DC, Jusko WJ, Androulakis IP. Identification of global transcriptional dynamics. PLoS One. 2009 Jul 10;4(7):e5992. PMID: 19593450 [PubMed - in process]
- Almon, R.R., Yang, E., Lai, W., Androulakis, I.P., DuBois, D.C., and Jusko, W.J. Circadian variations in liver gene expression: relationships to drug actions.Sep;326(3):700-16. Epub 2008 Jun 18. PMID: 18562560 J. Pharmacol. Exp. Therapeutics 2008.
- Almon, R.R., Yang, E., Lai, W., Andoulakis, I.P., Ghimbovschi, S., Hoffman, E.P., Jusko, W.J., and DuBois, D.C. Relationships between circadian rhythms and modulation of gene expression by glucocorticoids in skeletal muscle. Oct;295(4):R1031-47. Epub 2008 Jul 30. PMID: 18667713 Am J. Physiology 2008.
- Earp, J.C., DuBois, D.C., Molano, D.S., Pyszczynski, N.A., Almon, R.R., and Jusko, W.J. Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: Mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis. J. Pharmacol. Exp. Therapeutics, 326: 546-554, 2008.
- Earp, J.C., DuBois, D.C., Molano, D.S., Pyszczynski, N.A., Keller, C.E., Almon, R.R., and Jusko, W.J. Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: Mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats. J. Pharmacol. Exp. Therapeutics: 326: 532-545, 2008
- Yao, Z., DuBois, D.C.., Almon, R.R., and Jusko, W.J. Pharmacodynamic/ pharmacogenomic modeling of the insulin resistant genes in rat muscle after methylprednisolone treatment: Exploring regulatory signaling cascades. Gene Reg. Sys. Biol., 2: 141-161, 2008.
- Hazra, A., DuBois, D.C., Almon, R.R., Snyder, G.H., and Jusko, W.J. Pharmacodynamic modeling of acute and chronic effects of methylprednisolone on hepatic urea cycle genes in rats. Gene Reg. Sys. Biol., 2: 1-19, 2008.
- Yang, E., Almon, R.R., DuBois, D.C., Jusko, W.J., and Androulakis, I.P. Extracting global System dynamics of corticosteroid genomic effects in rat liver. J. Pharmacol. Exp. Therapeutics. 324: 1243-1254, 2008
- Yao Z, DuBois DC, Almon RR, Jusko WJ. Pharmacokinetic/pharmacodynamic modeling of corticosterone suppression and lymphocytopenia by methylprednisolone in rats. J Pharm Sci. 2008 Jul;97(7):2820-32.
- Hazra A, Pyszczynski NA, DuBois DC, Almon RR, Jusko WJ. Modeling of corticosteroid effects on hepatic low-density lipoprotein receptors and plasma lipid dynamics in rats. Pharm Res. 2008 Apr;25(4):769-80.
- Yao, Z., Hoffman, E.P., Ghimbovschi, S., DuBois, D.C., Almon, R.R., and Jusko, W.J. Mathematical modeling of corticosteroid pharmacogenomics in rat muscle following acute and chronic methylprednisolone dosing. Mol. Pharm., 5: 328-339, 2008.
- Hazra A, Pyszczynski N, DuBois DC, Almon RR, Jusko WJ. Modeling receptor/gene-mediated effects of corticosteroids on hepatic tyrosine aminotransferase dynamics in rats: dual regulation by endogenous and exogenous corticosteroids. J Pharmacokinet Pharmacodyn.: 34(5):643-67, 2007
- Hazra A, Pyszczynski N, DuBois DC, Almon RR, Jusko WJ. Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats. Biopharm Drug Dispos: 28(6):263-73, 2007
- Almon RR, DuBois DC, Yao Z, Hoffman EP, Ghimbovschi S, Jusko WJ. Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens. Physiol Genomics. 30(3):282-99, 2007
- Yang E, Simcha D, Almon RR, Dubois DC, Jusko WJ, Androulakis IP. Context specific transcription factor prediction. Ann Biomed Eng. 35(6):1053-67, 2007
- Androulakis IP, Yang E, Almon RR. Analysis of time-series gene expression data: methods, challenges, and opportunities. Annu Rev Biomed Eng. 9:205-28, 2007
- Yao Z, Zhao B, Hoffman EP, Ghimbovschi S, DuBois DC, Almon RR, Jusko WJ. Application of scaling factors in simultaneous modeling of microarray data from diverse chips. Pharm Res. 24(4):643-9, 2007
- Almon RR, DuBois DC, Jusko WJ. A microarray analysis of the temporal response of liver to methylprednisolone: a comparative analysis of two dosing regimens. Endocrinology. 148(5):2209-25, 2007
- Hazra A, DuBois DC, Almon RR, Jusko WJ. Assessing the dynamics of nuclear glucocorticoid-receptor complex: adding flexibility to gene expression modeling. J Pharmacokinet Pharmacodyn. 34(3):333-54, 2007
- Samtani MS, Pyszczynski NA, DuBois D, Almon RR, and Jusko
WJ, Modeling Glucocorticoid-Mediated Fetal Lung
Maturation II. Temporal Patterns of Gene Expression in
Fetal Rat Lung,
Journal of Pharmacology and Experimental
Therapeutics, 317, 127-138, 2006.
- Samtani MS, Pyszczynski NA, DuBois D, Almon RR, and Jusko
WJ, Modeling Glucocorticoid-Mediated Fetal Lung
Maturation I. Temporal Patterns of Corticosteroids in Rat
Pregnancy
Journal of Pharmacology and Experimental
Therapeutics, 317, 117-126, 2006.
- Yao Z, DuBois DC, Almon RA, and Jusko WJ, Modeling
Circadian Rhythms of Glucocorticoid Receptor and
Glutamine Synthetase Expression in Rat Skeletal Muscle
Pharmaceutical Research, 1-10, 2006.
- Almon RR, DuBois DC, Jusko WJ. Corticosteroid
Regulated Genes in Rat Kidney: Mining Time Series Array
Data
American Journal Physiology, Endocrinology and
Metabolism, 289, E870-E882, 2005.
- Almon RR, DuBois DC, Jin JY, Jusko WJ. The Response
of Liver to Methylprednisolone: An Approach to Mining a
Rich Microarray Time Series
American Association of Pharmaceutical Sciences
Journal 7, E156-E194, 2005.
- Almon RR, DuBois, DC, Jin, JY and Jusko, WJ, Temporal
profiling of the transcriptional basis for the
development of corticosteroid-induced insulin resistance
in rat muscle
Journal of Endocrinology (2005) 184,
219-232
- Almon RR, DuBois DC, Piel WH, Jusko WJ. The Genomic
Response of Skeletal Muscle to Methylprednisolone using
Microarrays: Tailoring Data Mining to the Structure of
the Pharmacogenomic Time Series,
Pharmacogenomics, 5: 525-552 (2004)
- Jin Y. Jin, Debra C. DuBois, Richard R. Almon, and
William J. Jusko. Receptor/Gene Mediated
Pharmacodynamic Effects of Methylprednisolone on
Phosphoenolpyruvate Carboxykinase Regulation in Rat Liver.
Journal Of Pharmacologyand Experimental
Therapeutics. 309: 328-339, 2004.
- Josephine Chen1, Po Zhao1, Donald Massaro2,
Linda B. Clerch, Richard R. Almon, Debra C. DuBois3,
4, William J. Jusko4, Eric P Hoffman1
The PERP GeneChip data wharehouse, and implementation of
a dynamic time series query tool (SGQT) with graphical
interface.
Nucleic Acid Research 32: 1-4, 2004
- Ramakrishnan, R., DuBois, D., Almon, R., Pyszczynski, N.,
and Jusko, W.,
Pharmacodynamics and Pharmacogenomics of
Methylprednisolone During Seven-day Infusion in Rats.
J. Pharmacology and Experimental
Therapeutics, 300: 245-256, 2002
- Ramakrishnan, R., DuBois, D., Almon, R., Pyszczynski, N.,
and Jusko, W.,
Fifth- Generation Model for Corticosteroid
Pharmacodynamics: Application to Steady-state Receptor
Down-regulation and Enzyme Induction Patterns during
Seven-day Continuous Infusion of Methylprednisolone in
Rat.
J. Pharmacokinetics and Pharmacodynamics
- Richard R. almon, Debra C. DuBois, Emily Bachman, Wei
Shi, Shuzhong Zhang, Robert M. Straubinger, and William J
Jusko
Pharmacodynamics and Pharmacogenomics of Diverse
Receptor-Mediated Effects of Methylprednisolone in Rats
using Microarray Analysis.
J. Pharmacokinetics and Pharmacodynamics
- Almon, R.R. and DuBois, D.C.
Tyrosine Transaminase.
Encyclopedia of Molecular Biology Vol. 5:
3297-3300
- Almon, R.R. and DuBois, D. C.
Quantitation of expressed message for Inducible
nitric oxide synthase (EC 1.14.13.39).
Methods in Enzymology
- Almon, R.R.
Immunosuppressive/Anti-inflammatory Drugs
Business Briefing Pharmatech 2002
- Han, Bing, Shi, Wei, Sagawa, Kazuko, DuBois, Debra, C.,
and Almon Richard, R (1998)
Can the Pharmacological Use of Growth Hormone
Facilitate Recovery of Muscle From Disuse
in"Adult" and "Old" animals
1998 Gerontology Society of America, winner
of the George Sacher Prize
- Sun, Y-N, McKAY, L.I., DuBois, D. C., Jusko, W.J., and
Almon, R. R. (1999)
Glucocorticoid Dynamics: A
Pharmacokinetic/Pharmacodynamic (PK/PD) Model for
Glucocorticoid Receptor Down Regulation and Glutamine
Synthetase Induction in Rat Skeletal Muscle by a Receptor
Gene Mediated Mechanism.
J. Pharmacology and Experimental
Therapeutics. 288:720-728
- Sagawa, K. DuBois, D. C., Almon, R. R., Murer, H., and
Morris (1998)
Cellular mechanisms of Renal Adaptation of Sodium
Dependent Sulfate Cotransport to Altered Dietary Sulfate
in Rats
J. Pharmacology and Experimental
Therapeutics 287:1056-1062
- Sun, Y-N, DuBois, D. C., Almon, R. R., and Jusko, W.J
(1998)
Fourth-Generation Model for Corticosteroid
Pharmacodynamics: A Model for Methylprednisolone Effects
on Receptor Gene-Mediated Glucocorticoid Receptor
Down-Regulation and Tyrosine Aminotransferase Induction
in Rat Liver.
J. Pharmacokinetics and Biopharmaceutics
26:289-317
- McKay, L.I., DuBois, D. C., Sun, Y-N., Jusko, W.J., and
Almon, R. R (1997)
Corticosteroid effects in skeletal muscle: coupled
dynamic response of glutamine synthetase induction and
glucocorticoid receptor autoregulation
Muscle and Nerve 20: 1318-1320
- Almon, R. R., DuBois, D. C (1996)
Drugs in Human Biology
McGraw-Hill, New York ISBN
0-07-001399-3.
- Lapier, T.K., Cerny, F.S., Almon, R.R., and Burton, H.B.
(1995)
Limb immobilization affects susceptibility to
contractionduced muscle injury.
Journal of Applied Physiology
78:1065-1069
- DuBois, D.C., Xu, Z.-X., McKay, L., Almon, R.R.,
Pyszcznski, N., and Jusko, W.J. (1995)
Differential dynamics of receptor downegulation and
tyrosine aminotransferase induction following
glucocorticoid treatment
Biochemistry and Molecular Biology
54:237-243
- DuBois, D. C., Almon, R. R. and, Jusko, W (1993)
Molar quantification of specific messenger
ribonucleic acid expression in Northern hybridization
using cRNA standards
Analytical Biochemistry 210:
140-144
- Zemkova, H., Teisinger, J., Almon, R. R., Vejsada, R.,
Hnik, P. and Vyskocil, F (1990)
Immobilization atrophy and membrane properties in rat
skeletal muscle fibers
Eur. J of Physiology. Pfugers Arch 416:
126-129
- Almon, R. R. and DuBois, D. C (1990)
Fiber-type discrimination in disuse and
glucocorticoid induced atrophy
Med. Sci. Sports Exerc 22: 304-311
- Almon, R. R. and DuBois, D. C (1988)
Adrenalectomy eliminates both fiber-type differences
and starvation effects on denervated muscle
Am. J. Physiology 255: E850-856
- DuBois, D. C. and Almon, R. R (1984)
Glucocorticoid sites in skeletal muscle:
adrenalectomy, maturation, fiber type and sex.
Am. J. Physiology 247: E118-E125
- DuBois, D. C. and Almon, R. R (1980)
Disuse atrophy of skeletal muscle is associated with
an increase in number of glucocorticoid receptors
Endocrinology 107: 1649-1651
- Almon, R. R. and Appel, S.H (1976)
Cholinergic sites in skeletal muscle, II. Interaction
of each site with agonists and antagonists
Biochemistry 15: 3667-3671
- Almon, R. R. and Appel, S.H (1976)
Cholinergic sites in skeletal muscle, I. Denervation
effects
Biochemistry 15: 3662-3667
- Almon, R.R. and Appel, S.H (1975)
Interaction of Myasthenic serum globulin with the
acetylcholine receptor
Biochem. Biophys. Acta 393: 66-77
- Almon, R. R., Andrew, C. G. and Appel, S.H (1974)
Acetylcholine receptor in normal and denervated slow
and fast muscle
Biochemistry13: 5522-5528
- Andrew, C.G., Almon, R.R. and Appel, S.H (1975)
Macromolecular characterization of muscle membranes:
Endogenous membrane kinase and phosphorylated protein
substrate from normal and denervated muscle
J. Biological. Chemistry 250:
3972-3980
- Almon, R.R., Andrew, C.G., and Appel, S.H. (1974)
Serum globulin In Myasthenia Gravis: Inhibition of
alpha bungarotoxin binding to acetylcholine receptors
Science 186: 55-57