BIOGRAPHICAL SKETCH Mark E. Lowe, M.D., Ph.D Professor of ...

BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
Mark E. Lowe, M.D., Ph.D
eRA COMMONS USER NAME
MELOWE
POSITION TITLE
Professor of Pediatrics
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
Washington University, St. Louis B.A. 1973 Biology
University of Pennsylvania, PA Ph.D. 1977 Biochemistry
University of Miami, FL M.D. 1984 Medicine
A. Positions and Honors.
Positions and Employment
1973-77 NIH Predoctoral Fellow, University of Pennsylvania Department of Biochemistry, Philadelphia, PA
1977-81 NIH Staff Fellow, NIH, NIADKK, Laboratory of Biochemistry and Metabolism, Bethesda, MD
1981-82 NIH Senior Staff Fellow, NIH, NIADKK Pediatric Metabolism Branch, Bethesda, MD
1984-85 Pediatric Intern, St. Louis Children’s Hospital at Washington University Medical Center, St. Louis,
MO
1984-89 Assistant in Pediatrics, Washington University School of Medicine, St. Louis, MO
1985-86 Pediatric Resident, St. Louis Children’s Hospital at Washington University Medical Center, St. Louis,
MO
1986-89 Fellow in Pediatrics (Gastroenterology/Nutrition) St. Louis Children’s Hospital at Washington
University Medical Center, St. Louis, MO
1989-90 Instructor in Pediatrics, St. Louis Children’s Hospital at Washington University Medical Center, St.
Louis, MO
1990-97 Assistant Professor in Pediatrics, St. Louis Children’s Hospital at Washington University Medical
Center, St. Louis, MO
1995-97 Assistant Professor in Molecular Biology and Pharmacology at Washington University Medical
Center, St. Louis, MO
1997-03 Associate Professor in Pediatrics, St. Louis Children’s Hospital at Washington University Medical
Center, St. Louis, MO
1997-03 Associate Professor in Molecular Biology and Pharmacology at Washington University Medical
Center, St. Louis, MO
2003- Professor in Pediatrics, Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical
Center, Pittsburgh, PA
2004- Professor in Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA
Other Experience and Professional Memberships
1992 American Society for Biochemistry and Molecular Biology
1993 Society for Pediatric Research
1993 American Gastroenterological Association
1993 American Association for the Advancement of Science
1996 North American Society for Pediatric Gastroenterology and Nutrition
2004 American Pediatric Society
Honors
1973 Omicron Delta Kappa
1992 AHA Established Investigatorship Award
1996 Mead Johnson Award for the American Institute of Nutrition

B. Selected Peer-Reviewed publications (in chronological order).
1. Lowe ME, Rosenblum JL, and Strauss AW: Cloning and characterization of a cDNA encoding human
pancreatic lipase. J. Biol. Chem. 1989;264:20042-20048.
2. Lowe ME, Rosenblum JL, McEwen P, and Strauss AW: Isolation and characterization of a cDNA
encoding Human Colipase. Biochemistry 1990;29:823-828.
3. Sims HF, and Lowe ME: The human colipase gene: Isolation, chromosomal location, and tissue-specific
expression. Biochemistry 1992;31:7120-7125.
4. Lowe ME: The active-site residues and interfacial binding of human pancreatic lipase. J. Biol. Chem.
1992;267:17069-17073.
5. Kumar BV, Aleman-Gomez JA, Colwell N, Lopez-Candales A, Bosner MS, Spilberg CA, Lowe ME, and
Lange LG: Structure of the human pancreatic cholesterol esterase gene. Biochemistry 1992;31:6077-
6081.
6. Sims HF, Jennens M, and Lowe ME. The human pancreatic lipase gene: structure and conservation of
an Alu sequence in the lipase gene family. Gene 1993;131:281-285.
7. Payne RM, Sims HF, Jennens ML, and Lowe ME. Rat pancreatic lipase and two related proteins:
enzymatic properties and mRNA expression during development. Am. J. Physiol. 994;29:G914-G921.
8. Lowe ME. Human pancreatic procolipase expressed in insect cells: purification and characterization.
Protein expression and Purification 5/6:583-586, 1994.
9. Jennens ML and Lowe ME. A surface loop covering the active site of human pancreatic lipase influences
interfacial activation and lipid binding. J. Biol. Chem. 269(41):25470-25474, 1994.
10. Jennens ML and Lowe ME. The C-terminal domain of human pancreatic lipase is required for stability and
full activity but not colipase reactivation. J. Lip. Res. 36:1029-1030, 1995.
11. Jennens ML and Lowe ME. Rat GP-3 is a pancreatic lipase with kinetic properties that differ from
colipase-dependent pancreatic lipase. J. Lip. Res. 36:2374-2382, 1995.
12. Kullman J, Gisi C and Lowe ME. Dexamethasone regulates expression of pancreatic lipase and two
related proteins in AR42J cells. Am. J. Physiol. 270:G746-G751, 1996.
13. Lowe ME. Mutation of the catalytic site Asp 177 to Glu 177 in human pancreatic lipase produces an active
lipase with decreased conformational stability. Biochem Biophys Acta 1302:177-183, 1996.
14. Andersson L, Carriere F, Lowe ME, Nilsson A and Verger R. Pancreatic lipase related protein 2 but not
classical pancreatic lipase hydrolyzes galactolipids. Biochem Biophys Acta 1302:236-240, 1996.
15. Lowe ME. Colipase stabilizes the lid domain of pancreatic triglyceride lipase. J Biol Chem 272(1):9-12,
1997.
16. Cordle RA and Lowe ME. Purification and characterization of human procolipase expressed in yeast cells.
Protein Expression and Purification 13(1):30-35, 1998.
17. Yang Y and Lowe ME. Human pancreatic triglyceride lipase expressed in yeast cells: Purification and
characterization. Protein Expression and Purification. 13(1):36-40, 1998.
18. Cordle R and Lowe ME. The hydrophobic surface of colipase influences lipase activity at an oil-water
interface. J. Lip. Res. 1998;39:1759-1767.
19. Winzell-Sorhede M, Lowe ME and Erlanson-Albertsson, C. Rat gastric procolipase: Sequence, expression
and secretion during high-fat feeding. Gastroenterology. 1998;115:1179-1185.
20. Lowe ME, Kaplan MH, Jackson-Grusby L, D'Agostino D and Grusby MJ. Decreased neonatal dietary fat
absorption and T cell cytotoxicity in pancreatic lipase-related protein 2-deficient mice. J. Biol. Chem.
1998;273(47):31215-31221.
21. Roussel A, Yang Y, Ferrato F, Verger R, Cambillau C and Lowe ME. Structure and activity of rat
pancreatic lipase-related protein 2. J. Biol. Chem. 1998;273(48):32121-32128.
22. Yang Y and Lowe ME. The open lid mediates pancreatic lipase function. J. Lipid Res. 2000; 41:48-57.
23. Yang Y, Sanchez D, Figarella C, and Lowe ME. Discoordinate expression of pancreatic lipase and two
related proteins in the human fetal pancreas. Pediatr. Res. 2000;47:184-188.
24. Crandall WV and Lowe ME. Colipase residues Glu 64 and Arg 65 are essential for normal lipase mediated
fat digestion in the presence of bile salt micelles. J. Biol. Chem. 2001;275:12505-12512.
25. Bauer VW, Squire TL, Lowe ME, and Andrews MT. Novel expression of pancreatic triacylglycerol in white
adipose tissues confers low-temperature lipolysis in a hibernating animal. Am. J. Physiol. 2001;
281:R1186-R1192.

25. D’Agostino D, Cordle RA, Kullman J, Erlanson-Albertsson C, Muglia LJ, and Lowe ME. Decreased
postnatal survival and altered body weight regulation in procolipase deficient mice. J. Biol. Chem. 2002;
277:7170-7177.
26. Lowe ME and Keating JP. Persistent hyperlipasemia caused by macrolipase in an adolescent. J. Pediat.
2002; 141:129-131.
27. Chahinian H, Bezzine S, Ferrato F, Ivanonva MG, Perez B, Lowe ME, and Carriere F. The beta 5’ loop of
pancreatic lipase C2-like domain plays a critical role in lipase-lipid interactions. Biochemistry 2002,
41:13725-13735.
28. Imamura T, Asada M, Vogt SK, Rudnick DA, Lowe ME, and Muglia LJ. Protection from pancreatitis by the
zymogen granule membrane protein integral membrane-associated protein-1. J. Biol. Chem. 2002,
277:50725-50733.
29. Rippe C, Berger K, Mei J, Lowe ME, and Erlanson-Albertsson C. Effect of long-term high-fat feeding on
the expression of pancreatic lipases and adipose tissue uncoupling proteins in mice. Pancreas 2003,
26:E36-42.
30. Squire TL, Lowe ME, Bauer VW, Andrews MT. Pancreatic triacylglycerol lipase in a hibernating mammal.
II. Cold-adapted function and differential expression. Physiol Genomics 2003;16(1):131-40.
31. Tsujita T, Sumiyoshi M, Takaku T, Momsen WE, Lowe ME, Brockman HL. Inhibition of lipases by epsilon
-polylysine. J Lipid Res 2003; 44:2278-2286.
32. D'Agostino D, Lowe ME. Pancreatic lipase-related protein 2 is the major colipase-dependent pancreatic
lipase in suckling mice. J Nutr 2004;134(1):132-4.
33. Moulton DE, Crandall W, Lakhani R and Lowe ME. Expression of a novel cadherin in the mouse and
human intestine. Pediatr Res 2004; 55:1-8.
34. Momsen WE, Mizuno NK, Lowe ME and Brockman HL. Real-time measurement of solute partitioning to
lipid monolayers. Anal Biochem 2005;346:139-49.
35. Freie AB, Ferrato F, Carriere F and Lowe ME. Val407 and Ile408 in the β5’ loop of pancreatic lipase
mediate lipase-colipase interactions in the presence of bile salt micelles. J Biol Chem 2006; 281: 7893-
7900.
36. D'Silva S, Xiao X, Lowe ME. A polymorphism in the gene encoding procolipase produces a colipase,
Arg92Cys, with decreased function against long-chain triglycerides. J Lipid Res 2007 Aug 22.
37. Li X, Lindquist S, Lowe ME, Noppa L, Hernell O. Bile Salt-Stimulated Lipase and Pancreatic Lipase-
Related Protein 2 Are the dominating lipases in neonatal fat digestion in mice and rats. Pediatr Res 2007;
62:537-541.
38. Miller R and Lowe ME. Carboxyl ester lipase from either mother’s milk or from the pancreas is required for
efficient dietary triglyceride digestion in suckling mice. J Nutri 2008; 138:927-930.
39. Freie AB, Dub RE, Xia X and Lowe ME. Trp-1007 and Trp-253 account for the increased steady-state
fluorescence that accompanies the conformational change in human pancreatic triglyceride lipase induced
by tetrahydrolipstatin and bile salt. J Biol Chem 2009; in press.
Selected Invited Reviews
1. Lowe ME. Structure and function of pancreatic lipase and colipase. Ann Rev Nutr 17:141-58, 1997.
2. Lowe ME. Site-specific mutagenesis of human pancreatic lipase. Meth Enzymol 284:157-170, 1997.
3. Lowe ME. New pancreatic lipases: Gene expression, protein secretion and the newborn. Meth Enzymol
284:285-297, 1997.
4. Lowe ME. Assay of pancreatic triglyceride lipase and colipase. Methods Mol. Biol. 109:59-70, 1998.
5. D'Agostino, D. and M. Lowe. Intestinal expression of pancreatic lipase related protein 2. In: Lipases and
Lipids: Structure, Function and Biotechnological Applications. (G. Kokotos and V. Constantinou-Kokotou,
eds) Crete University Press, Crete, Greece. pp 143-152, 2000.
6. Lowe ME. Properties and function of pancreatic lipase related protein 2. Biochimie 82:997-1004, 2000.
7. Lowe ME. 2000. Molecular mechanisms of pancreatic triglyceride lipase and colipase. In: Intestinal Lipid
Metabolism (Mansbach, Tso, and Kuksis, eds) Kluwer Academic/Plenum Publishers, New York, NY. pp
37-54, 2001.
8. Lowe ME. Colipase, in: Wiley Encyclopedia of Molecular Medicine. John Wiley & Sons, Inc. 2002;869-
871.
9. Lowe ME. The triglyceride lipases of the pancreas. J Lip Res 2002; 43:2007-2016.

10. Lowe, ME. Pancreatic Triglyceride Lipase. In: Encyclopedia of Gastroenterology (Johnson, LR, ed.)
Academic Press, San Diego, CA vol 1, pp 89-90, 2004.
11. Whitcomb DC and Lowe ME. Human pancreatic digestive enzymes. Dig Dis Sci 2007; 52:1-17.
C. Research Support
Ongoing Research Support
R01 HL49180-14 Brockman (PI) 08/01/07 - 07/30/12
NIH/NHLBI
Lipase Control by Protein-induced Lipid Reorganization
Dr. Lowe provides recombinant lipase and colipase as well as mutants for Dr. Brockman’s ongoing studies.
Role: sub-contract
Pending Research Support
R21 DK078538-01 Lowe (PI)
NIH/NIDDK 07/01/09-09/30/11
Circadian Expression of Procolipase in the Liver: A Metabolic Signal.
The goals of this study are to characterize the ectopic liver expression of procolipase that is induced by
constant darkness and fasting. We will determine the effects of expression on feeding behavior, determine if
AMPK pathways mediate the expression, and identify elements in the procolipase gene controlling expression
in the liver.
R01 DK080820-01 Lowe (PI)
NIH/NIDDK 07/01/09-09/30/11
Molecular Mechanisms of Dietary Fat Digestion by Pancreatic Lipases
The goals of this study are to identify the structures that dictate substrate specificity in pancreatic lipases, to
identify the structures in the colipase-lipase complex that mediate absorption to lipid surfaces, and to identify
the structures that mediate the interaction between colipase and lipase.