Research Professor, Department of Biomedical Sciences
Contact Information
Email:Biosketch
Rolf Kletzien, PhD, is co-founder, senior vice president-research, and a board member for Metabolic Solutions Development Company (MSDC) in Kalamazoo, Michigan, a drug discovery and development company investigating new molecular targets and developing novel therapeutics to treat metabolic diseases associated with age-related mitochondrial dysfunction, especially insulin resistance and type 2 diabetes.
Dr. Kletzien is a graduate of University of Wisconsin in Madison, Wisconsin. He also earned his doctorate in oncology from University of Wisconsin.
Prior to founding MSDC, Dr. Kletzien worked for The Upjohn Company, Pharmacia & Upjohn, Pharmacia Corporation, and Pfizer Corporation most recently, where he served as vice president of genomics & biotechnology. He has four patents to his name and has extensive research grant experience. He also has a considerable publication list, with more than 70 articles he has contributed to.
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Education and Training
- PhD 1974, Oncology, University of Wisconsin-Madison
- BS 1970, Biochemistry, University of Wisconsin-Madison
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Research
- Oncology
- Molecular Biology
- Biochemistry
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Publications
Colca J.R., Tanis S.P., Kletzien R.F., Finck B.N. Insulin sensitizers in 2023: lessons learned and new avenues for investigation Expert Opinion on Investigational Drugs. 2023;32:803-811.
Kletzien R.F., Berdanier C.D. Glucose-6-phosphate dehydrogenase: Diet and hormonal influences on de novo enzyme synthesis Nutrition and Gene Expression. 2018:187-206.
Tanis S.P., Colca J.R., Parker T.T., Artman G.D., Larsen S.D., McDonald W.G., Gadwood R.C., Kletzien R.F., Zeller J.B., Lee P.H., Adams W. PPARγ-sparing thiazolidinediones as insulin sensitizers. Design, synthesis and selection of compounds for clinical development Bioorganic and Medicinal Chemistry. 2018;26(22):5870-5884.
Vigueira P., McCommis K.S., Hodges W.T., Schweitzer G.G., Cole S.L., Oonthonpan L., Taylor E.B., McDonald W.G., Kletzien R.F., Colca J.R., Finck B.N. The beneficial metabolic effects of insulin sensitizers are not attenuated by mitochondrial pyruvate carrier 2 hypomorphism Experimental Physiology. 2017;102(8):985-999.
McCommis K.S., Chen Z., Fu X., McDonald W.G., Colca J.R., Kletzien R.F., Burgess S.C., Finck B.N. Loss of mitochondrial pyruvate carrier 2 in the liver leads to defects in gluconeogenesis and compensation via pyruvate-alanine cycling Cell Metabolism. 2015;22(4):682-694.
Colca J., Mcdonald W., Kletzien R. Mitochondrial target of thiazolidinediones Diabetes, Obesity and Metabolism. 2014;16(11):1048-1054.
Colca J., Tanis S., McDonald W., Kletzien R. Insulin sensitizers in 2013: New insights for the development of novel therapeutic agents to treat metabolic diseases Expert Opinion on Investigational Drugs. 2014;23(1):1-7.
Vigueira P., McCommis K.S., Schweitzer G.G., Remedi M.S., Chambers K.T., Fu X., McDonald W.G., Cole S.L., Colca J.R., Kletzien R.F., Burgess S.C., Finck B.N. Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion Cell Reports. 2014;7(6):2042-2053.
Colca J.R., McDonald W.G., Cavey G.S., Cole S.L., Holewa D., Brightwell-Conrad A.S., Wolfe C.L., Wheeler J.S., Coulter K.R., Kilkuskie P.M., Gracheva E., Korshunova Y., Trusgnich M., Karr R., Wiley S.E., Divakaruni A.S., Murphy A.N., Vigueira P.A., Finck B.N., Kletzien R.F. Identification of a Mitochondrial Target of Thiazolidinedione Insulin Sensitizers (mTOT)-Relationship to Newly Identified Mitochondrial Pyruvate Carrier Proteins PLoS ONE. 2013;8(5)
Rohatgi N., Aly H., Marshall C.A., McDonald W.G., Kletzien R.F., Colca J.R., McDaniel M.L. Novel Insulin Sensitizer Modulates Nutrient Sensing Pathways and Maintains β-Cell Phenotype in Human Islets PLoS ONE. 2013;8(5)
Chen Z., Vigueira P.A., Chambers K.T., Hall A.M., Mitra M.S., Qi N., McDonald W.G., Colca J.R., Kletzien R.F., Finck B.N. Insulin resistance and metabolic derangements in obese mice are ameliorated by a novel peroxisome proliferator-activated receptor γ-sparing thiazolidinedione Journal of Biological Chemistry. 2012;287(28):23537-23548.
Colca J.R., Kletzien R.F. Current and emerging strategies for treating dyslipidemia and macrovascular disease. Advances in pharmacology (San Diego, Calif.). 2009;57:237-251.
Colca J., Kletzien R. What has prevented the expansion of insulin sensitisers? Expert Opinion on Investigational Drugs. 2006;15(3):205-210.
Sadhukhan R., Leone J., Lull J., Wang Z., Kletzien R., Heinrikson R., Tomasselli A. An efficient method to express and refold a truncated human procaspase-9: A caspase with activity toward Glu-X bonds Protein Expression and Purification. 2006;46(2):299-308.
Qahwash I., He W., Tomasselli A., Kletzien R.F., Yan R. Processing amyloid precursor protein at the β-site requires proper orientation to be accessed by BACE1 Journal of Biological Chemistry. 2004;279(37):39010-39016.
Qahwash I., Weiland K.L., Lu Y., Sarver R.W., Kletzien R.F., Yan R. Identification of a mutant amyloid peptide that predominantly forms neurotoxic protofibrillar aggregates Journal of Biological Chemistry. 2003;278(25):23187-23195.
Ulrich R., Cramer C., Adams L., Kletzien R. Activation and glucagon regulation of mitogen-activated protein kinases (MAPK) by insulin and epidermal growth factor in cultured rat and human hepatocytes Cell Biochemistry and Function. 1998;16(2):77-85.
Stapleton S., Garlock G., Foellmi-Adams L., Kletzien R. Selenium: Potent stimulator of tyrosyl phosphorylation and activator of MAP kinase Biochimica et Biophysica Acta - Molecular Cell Research. 1997;1355(3):259-269.
Foellmi-Adams L.A., Wyse B.M., Herron D., Nedergaard J., Kletzien R.F. Induction of uncoupling protein in brown adipose tissue. Synergy between norepinephrine and pioglitazone, an insulin-sensitizing agent Biochemical Pharmacology. 1996;52(5):693-701.
Harris P., Foehmi-Adams L., Kletzien R. JNK activation in 3T3-L1 cells by tumor necrosis factor- (TNF-α) FASEB Journal. 1996;10(6)
Heinrikson R.L., Manning A.M. Identification of signal-induced IκB-α kinases in human endothelial cells Journal of Biological Chemistry. 1996;271(33):19680-19688.
Cramer C., Cooke S., Ginsberg L., Kletzien R., Stapleton S., Ulrich R. Upregulation of glucose‐6‐phosphate dehydrogenase in response to hepatocellular oxidative stress: Studies with diquat Journal of Biochemical Toxicology. 1995;10:293-298.
Harris P.K.W., Kletzien R.F. Localization of a pioglitazone response element in the adipocyte fatty acid-binding protein gene Molecular Pharmacology. 1994;45(3):439-445.
Kletzien R.F., Harris P.K.W., Foellmi L.A. Glucose-6-phosphate dehydrogenase: A "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress FASEB Journal. 1994;8(2):174-181.
Stapleton S.R., Stevens G.J., Teel J.F., Rank K., Berg E.A., Wu J.Y., Ginsberg L.C., Kletzien R.F. Effects of acetaldehyde on glucose-6-phosphate dehydrogenase activity and mRNA levels in primary rat hepatocytes in culture Biochimie. 1993;75:971-976.
Kletzien R.F., Clarke S.D., Ulrich R.G. Enhancement of adipocyte differentiation by an insulin-sensitizing agent Molecular Pharmacology. 1992;41(2):393-398.
Kletzien R.F., Foellmi L.A., Harris P.K.W., Wyse B.M., Clarke S.D. Adipocyte fatty acid-binding protein: Regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent Molecular Pharmacology. 1992;42(4):558-562.
Ulrich R., Aspar D., Cramer C., Kletzien R., Ginsberg L. Isolation and culture of hepatocytes from the cynomolgus monkey (Macaca fascicularis) In Vitro Cellular &Developmental Biology. 1990;26:815-823.
Prostko C.R., Fritz R.S., Kletzien R.F. Nutritional regulation of hepatic glucose-6-phosphate dehydrogenase. Transient activation of transcription Biochemical Journal. 1989;258(1):295-299.
Fritz R.S., Kletzien R.F. Regulation of glucose-6-phosphate dehydrogenase by diet and thyroid hormone Molecular and Cellular Endocrinology. 1987;51(1-2):13-17.
McClung J., Ulrich R., Kletzien R. Erythrocyte-mediated microinjection of horseradish peroxidase into BHK cells - Subcellular localization by light and electron microscopy Molecular and Cellular Biochemistry. 1987;73(1):21-27.
Fritz R.S., Stumpo D.J., Kletzien R.F. Glucose-6-phosphate dehydrogenase mRNA sequence abundance in primary cultures of rat hepatocytes. Effect of insulin and dexamethasone Biochemical Journal. 1986;237(2):617-619.
McClung J.K., Johnson R.R., Kletzien R.F. Microinjection of the catalytic subunit of cyclic adenosine 3',5'-monophosphate dependent protein kinase into a human mammary carcinoma cell line Journal of Nutrition Growth and Cancer. 1986;3(1):13-22.
McClung J.K., Dreher K.L. Molecular cloning of DNA sequences complementary to rat liver glucose-6-phosphate dehydrogenase mRNA. Nutritional regulation of mRNA levels Journal of Biological Chemistry. 1985;260(9):5621-5624.
Prostko C.R., Kletzien R.F. Regulation of hepatic mRNA coding for glucose-6-phosphate dehydrogenase Federation Proceedings. 1985;44(3)
Stumpo D.J., Kletzien R.F. The effect of ethanol, alone and in combination with the glucocorticoids and insulin, on glucose-6-phosphate dehydrogenase synthesis and mRNA in primary cultures of hepatocytes Biochemical Journal. 1985;226(1):123-130.
Stumpo D.J., Prostko C.R., Kletzien R.F. Ethanol-glucocorticoid regulation of hepatic glucose-6-phosphate dehydrogenase Alcohol. 1985;2(1):169-172.
Kelley D.S., Kletzien R.F. Ethanol modulation of the hormonal and nutritional regulation of glucose 6-phosphate dehydrogenase activity in primary cultures of rat hepatocytes Biochemical Journal. 1984;217(2):543-549.
McClung J.K., Kletzien R.F. Analysis of BHK cell growth kinetics after microinjection of catalytic subunit of cyclic AMP-dependent protein kinase Molecular and Cellular Biology. 1984;4(6):1079-1085.
STUMPO D.J., KLETZIEN R.F. Regulation of glucose‐6‐phosphate dehydrogenase mRNA by insulin and the glucocorticoids in primary cultures of rat hepatocytes European Journal of Biochemistry. 1984;144(3):497-502.
Stumpo D.J., Kletzien R.F. Glucocorticoid and insulin regulation of hepatic mRNA coding for glucose-6-phosphate dehydrogenase Federation Proceedings. 1984;43(7)
Kletzien R.F., Weber C.A., Butcher F.R., Stumpo D.J. Glucagon and choleragen stimulation of glycogenolysis in primary cultures of adult rat liver parenchymal cells: Lack of involvement of the glucocorticoids Journal of Cellular Physiology. 1982;110(3):304-310.
Quinlan D., Todderud C., Kelley D., Kletzien R. Sodium-gradient-stimulated transport of L-alanine by plasma-membrane vesicles isolated from liver parenchymal cells of fed and starved rats. Crucial role of the adrenal glucocorticoids Biochemical Journal. 1982;208(3):685-693.
Weber C.A., Kletzien R.F. Hormonal and nutritional factors influencing glycogen deposition in primary cultures of rat liver parenchymal cells Journal of Cellular Physiology. 1982;110(3):300-303.
Keith Mcclung J., Kletzien R.F. The effect of nutritional status and of glucocorticoid treatment on the protein kinase isozyme pattern of liver parenchymal cells BBA - General Subjects. 1981;676(3):300-306.
Kletzien R. Nuclear-membrane-associated protein kinase and substrates. The effect of growth state on activity and specificity. The Biochemical journal. 1981;196(3):853-859.
Kletzien R.F., Weber C.A., Stumpo D.J. Coordinate regulation of gluconeogenesis by the glucocorticoids and glucagon: Evidence for acute and chronic regulation by glucagon Journal of Cellular Physiology. 1981;109(1):83-90.
Stumpo D.J., Kletzien R.F. Gluconeogenesis in rat liver parenchymal cells in primary culture: Permissive effect of the glucocorticoids on glucagon stimulation of gluconeogenesis Journal of Cellular Physiology. 1981;107(1):11-19.
Gross R.L., Kletzien R.F., Butcher F.R. Characterization of cytochalasin B binding to adult rat liver parenchymal cells in primary culture Biochimica et Biophysica Acta - Biomembranes. 1980;602(3):635-643.
Kletzien R. Nucleocytoplasmic transport of RNA. The effect of 3'-deoxyadenosine triphosphate on RNA release from isolated nuclei Biochemical Journal. 1980;192(2):753-759.
Kletzien R.F. Coordinate regulation of the phosphorylation state of pyruvate kinase by glucocorticoids and cyclic AMP Journal of Cell Biology. 1980;87(2 II)
Kletzien R.F., Day P. Modulation of the G<inf>0</inf> to S phase transit time by insulin: Potential involvement of protein phosphorylation Journal of Cellular Physiology. 1980;105(3):533-539.
Stumpo D.J., Kletzien R.F. Glucocorticoid permissive effects on glucagon-stimulated gluconeogenesis in primary cultures of adult rat liver parenchymal cells Journal of Cell Biology. 1980;87(2 II)
Todderud C.G., Kletzien R.F. Hormonal regulation of plasma membrane protein synthesis Journal of Cell Biology. 1980;87(2 II)
Pardee A., Dubrow R., Hamlin J., Kletzien R. Animal cell cycle. Annual review of biochemistry. 1978;47:715-750.
Kletzien R.F., Miller M., Pardee A.B. Unique cytoplasmic phosphoproteins are associated with cell growth arrest Nature. 1977;270(5632):57-59.
Phillips E., Kletzien R., Perdue J. A supravital polyaldehyde fixative for external cell surfaces Experimental Cell Research. 1977;105(1):51-62.
Kletzien R., Pariza M., Becker J., Potter V. Hormonal regulation of amino acid transport and gluconeogenesis in primary cultures of adult rat liver parenchymal cells Journal of Cellular Physiology. 1976;89(4):641-646.
Kletzien R., Perdue J. Regulation of sugar transport in chick embryo fibroblasts and in fibroblasts transformed by a temperature‐sensitive mutant of the rous sarcoma virus Journal of Cellular Physiology. 1976;89(4):723-728.
Pariza M.W., Butcher F.R., Kletzien R.F., Becker J.E., Potter V.R. Induction and decay of glucagon induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin Proceedings of the National Academy of Sciences of the United States of America. 1976;73(12):4511-4515.
Pariza M.W., Kletzien R.F., Butcher F.R., Potter V.R. Inductions By Hormones Added Singly, Simultaneously Or Sequentially: What Cultured Hepatocytes Can Tell Us About Metabolic Regulation In The Whole Animal Advances in Enzyme Regulation. 1976;14(C):103-115.
Potter V.R., Butcher F.R. Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin Journal of Biological Chemistry. 1976;251(10):3014-3020.
Kletzien R., Pariza M., Becker J., Potter V. A "permissive" effect of dexamethasone on the glucagon induction of amino acid transport in cultured hepatocytes Nature. 1975;256(5512):46-47.
Kletzien R., Pariza M., Becker J., Potter V. A method using 3-O-methyl-D-glucose and phloretin for the determination of intracellular water space of cells in monolayer culture Analytical Biochemistry. 1975;68(2):537-544.
Kletzien R., Pariza M., Becker J., Potter V. Hormonal and metabolic regulation of amino acid transport and gluconeogenesis in primary cultures of adult rat liver parenchymal cells Federation Proceedings. 1975;34(3)
Kletzien R., Perdue J. Regulation of sugar transport in chick embryo fibroblasts infected with a temperature-sensitive mutant of RSV Cell. 1975;6(4):513-520.
Kletzien R.F., Perdue J.F. Induction of sugar transport in chick embryo fibroblasts by hexose starvation. Evidence for transcriptional regulation of transport Journal of Biological Chemistry. 1975;250(2):593-600.
Kletzien R.F., Perdue J.F. Sugar transport in chick embryo fibroblasts. I. A functional change in the plasma membrane associated with the rate of cell growth Journal of Biological Chemistry. 1974;249(11):3366-3374.
Kletzien R.F., Perdue J.F. Sugar transport in chick embryo fibroblasts. II. Alterations in transport following transformation by a temperature sensitive mutant of the Rous sarcoma virus Journal of Biological Chemistry. 1974;249(11):3375-3382.
Kletzien R.F., Perdue J.F. Sugar transport in chick embryo fibroblasts. III. Evidence for post transcriptional and post translational regulation of transport following serum addition Journal of Biological Chemistry. 1974;249(11):3383-3387.
Kletzien R., Perdue J. Sugar transport in fibroblasts treated with serum and transformed by a temperature sensitive mutant of the Rous sarcoma virus Federation Proceedings. 1973;32(3 (I)):124.
Kletzien R.F., Perdue J.F. The inhibition of sugar transport in chick embryo fibroblasts by cytochalasin B. Evidence for a membrane-specific effect. Journal of Biological Chemistry. 1973;248(2):711-719.
Kletzien R.F., Perdue J.F., Springer A. Cytochalasin A and B. Inhibition of sugar uptake in cultured cells. Journal of Biological Chemistry. 1972;247(9):2964-2966.
Perdue J.F., Kletzien R., Wray V.L. The isolation and characterization of plasma membrane from cultured cells. IV. The carbohydrate composition of membranes isolated from oncogenic RNA virus-converted chick embryo fibroblasts BBA - Biomembranes. 1972;266(2):505-510.
Perdue J.F., Kletzien R., Miller K. The isolation and characterization of plasma membrane from cultured cells I. The chemical composition of membrane isolated from uninfected and oncogenic RNA virus-converted chick embryo fibroblasts BBA - Biomembranes. 1971;249(2):419-434.
Perdue J.F., Kletzien R., Miller K., Pridmore G., Wray V.L. The isolation and characterization of plasma membranes from cultured cells II. The chemical composition of membrane isolated from uninfected and oncogenic RNA virus-converted parenchyma-like cells BBA - Biomembranes. 1971;249(2):435-453.