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Curriculum Vita for Jerry L Brown PhD

CONTACT INFORMATIONName Jerry L BrownAddress 1020 Chaplin Ave, Lehigh Acres, FL 33971

Telephone (239) 491 0822Cell Phone (501) 276 2296Email jbrown7125@comcast.net

PERSONAL INFORMATIONPlace of Birth Magnet Cove, ARCitizenship USSex MaleMarital Status marriedSpouse's Name VeronikaChildren 1 adult son, Jason

EMPLOYMENT HISTORYUniversity of Colorado Health Sciences CenterBiochemistry and Molecular Genetics Department13001 E 17th PlaceAurora, Colorado

I joined the faculty of the University of Colorado Medical School, Department ofBiochemistry as an Assistant Professor in August of 1967. I remained with thisinstitution until my retirement, June 30, 1999. During this time I rose through theranks to Associate Professor and then Professor, the department name was changedtwice, first to Biochemistry, Biophysics and Genetics and eventually to Biochemistryand Molecular Genetics, I taught thousands of students in various courses (some of

these I directed) dealing with biochemistry and molecular biology. The studentpopulation that I taught came largely from the medical, dental, and graduateschools but I also lectured in courses for nursing, med tech, and pharmacy students.

The subject matter that I taught dealt with aspects of biochemistry and molecularbiology.

I was active in the graduate program at the University of Colorado. I taught in anddirected numerous courses for this program, accepted students from differentgraduate programs into my laboratory for training, and served on the thesiscommittees of numerous students. I was thesis advisor for 4 PhD students and 1masters student that successfully completed their degrees. I also trained two postdoctoral fellows, Ardythe McCracken and Vibha Sharma, who both spentapproximately three years in my laboratory learning and applying biochemical andmolecular biological techniques to the problems being addressed by my research.

Research

While at the University of Colorado my research was funded by grants that Iobtained from the NIH and the NSF. Due to my three moves after retiring I nolonger have specific information about these grants but during my 32 years at the

mailto:jbrown7125@comcast.netmailto:jbrown7125@comcast.net

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University of Colorado I raised several million dollars in research funds, which wasadequate to support my laboratory and research efforts.My research interests evolved as my career progressed. I initially studied proteinstructure and function which involved limited structural studies on terminal residuesof populations of proteins. I was interested in common structural features ofproteins and the roles these features may play (stability, localization, turnover rate

etc.) in the scheme of the organism. Perhaps the most significant finding fromthese efforts was the observation that the amino terminal amino acids of mostsoluble eukaryotic proteins are posttranslationally modified by -N-acetylation. Wewere unable to identify the purpose of this modification but did rule out some of themore obvious possibilities. To my knowledge, the function(s) of this modificationremains unknown.As these studies progressed I developed an interest in a human genetic disease, -1- proteinase inhibitor deficiency, caused by the impaired secretion variants of thisprotein. Individuals expressing a poorly secreted variant of -1- proteinaseinhibitor (A1Pi) are prone to develop pulmonary and/or liver problems as a result ofincreased destruction of these tissues due to their inability to adequately inhibitnormal circulating serine proteinases. In an attempt to identify the cause of the

defective secretion of the variant proteins we constructed variants of the inhibitorby oligonucleotide-directed mutagenesis of the cDNA specifying the most commonnormal variant (A1PiM). These variants were expressed in COS cells and thesecretion of the variant forms compared to the secretion of A1Pi M. At the time webegan these studies the defective secretion of the most common variant, A1PiZ,was assumed to be due to a mutation causing the disruption of a salt bridgebetween Lys 342 and Glu 290. Our results clearly demonstrated that this saltbridge was not necessary for the efficient secretion of A1Pi. Our experiments alsoshowed that A1PiZ had a greatly enhanced propensity for aggregation. Largeinclusion bodies containing this protein formed in cells expressing this variant. Itseems likely that the defective secretion of is related to the aggregation of thisprotein. Although we did not conclusively identify the cause of the inefficient

secretion of A1PiZ we did rule out the most popular explanation for this defect andprovided an alternate explanation for the secretion defect. We also constructedsome of the more rare variants of A1Pi that had been reported to be associated withpulmonary disease and were in the process of characterizing these variants at thetime of my retirement

PUBLICATIONS

1: Ray S, Mickleborough TD, Brown JL. Comparison of the properties of rarevariants of alpha1-proteinase inhibitor expressed in COS-1 cells and assessmentof their potential as risk factors in human disease. Biochim Biophys Acta. 2005

Jun 10;1740(3):390-402. Epub 2005 Apr 8. PubMed PMID: 15949707.

2: Brodbeck RM, Brown JL. Study of the roles of proline 391 and a highlyconserved sequence in the carboxyl-terminal region of members of the serpinfamily in the secretion of alpha 1-proteinase inhibitor. J Biol Chem. 1994 Jun24;269(25):17252-6. PubMed PMID: 8006033.

3: Leitinger B, Brown JL, Spiess M. Tagging secretory and membrane proteins with

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a tyrosine sulfation site. Tyrosine sulfation precedes galactosylation andsialylation in COS-7 cells. J Biol Chem. 1994 Mar 18;269(11):8115-21. PubMedPMID: 8132536.

4: Samandari T, Brown JL. A study of the effects of altering the sites forN-glycosylation in alpha-1-proteinase inhibitor variants M and S. Protein Sci.

1993 Sep;2(9):1400-10. PubMed PMID: 8401226; PubMed Central PMCID:PMC2142465.

5: Brodbeck RM, Samandari T, Brown JL. Effects of mutations that alter theGlu264-Lys387 salt bridge on the secretion of alpha-1-proteinase inhibitor. JBiol Chem. 1993 Mar 25;268(9):6771-6. PubMed PMID: 8454649.

6: Brodbeck RM, Brown JL. Secretion of alpha-1-proteinase inhibitor requires analmost full length molecule. J Biol Chem. 1992 Jan 5;267(1):294-7. PubMed PMID:1730596.

7: McCracken AA, Kruse KB, Valentine J, Roberts C, Yohannes TZ, Brown JL.

Construction and expression of alpha 1-proteinase inhibitor mutants and theeffects of these mutations on secretion of the variant inhibitors. J Biol Chem.1991 Apr 25;266(12):7578-82. PubMed PMID: 2019587.

8: Henry KW 2nd, Brown JL, McCracken AA. Selective enrichment fortemperature-sensitive secretion mutants of mammalian cells using plant lectin,concanavalin A. Somat Cell Mol Genet. 1990 Jul;16(4):297-304. PubMed PMID:2218719.

9: McCracken AA, Kruse KB, Brown JL. Molecular basis for defective secretion ofthe Z variant of human alpha-1-proteinase inhibitor: secretion of variants havingaltered potential for salt bridge formation between amino acids 290 and 342. Mol

Cell Biol. 1989 Apr;9(4):1406-14. PubMed PMID: 2786139; PubMed Central PMCID:PMC362557.

10: McCracken AA, Kruse KB, Brown JL. An enrichment selection for mutantsresulting from oligonucleotide-directed mutagenesis of double-stranded DNA.Biotechniques. 1988 Apr;6(4):332-9. PubMed PMID: 3078901.

11: McCracken AA, Emmett M, Crowle AJ, Brown JL. Studies on the secretion ofserum proteins from rat hepatoma cells. Hepatology. 1984 Jul-Aug;4(4):715-21.PubMed PMID: 6745862.

12: Emmett M, McCracken A, Brown JL, Crowle AJ. Crossed immunoelectrophoresisofrat serum. J Immunol Methods. 1984 Mar 16;67(2):279-88. PubMed PMID: 6200535.

13: Brown JL. A comparison of the turnover of alpha-N-acetylated andnonacetylated mouse L-cell proteins. J Biol Chem. 1979 Mar 10;254(5):1447-9.PubMed PMID: 762143.

14: Gade W, Brown JL. Purification and partial characterization of

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PubMed PMID: 4863045.

26: Brown JL, Brown DM, Zabin I. Beta-galactosidase: orientation and thecarboxyl-terminal coding site in the gene. Proc Natl Acad Sci U S A. 1967Sep;58(3):1139-43. PubMed PMID: 4861306; PubMed Central PMCID: PMC335759.

27: Brown JL, Koorajian S, Katze J, Zabin I. Beta-galactosidase. Amino-andcarboxyl-terminal studies. J Biol Chem. 1966 Jun 25;241(12):2826-31. PubMed PMID:5912357.28: BROWN JL, JOHNSTON JM. THE UTILIZATION OF I- AND 2-MONOGLYCERIDES FORINTESTINAL TRIGLYCERIDE BIOSYNTHESIS. Biochim Biophys Acta. 1964 Aug5;84:448-57.PubMed PMID: 14230819.

29: BROWN JL, JOHNSTON JM. THE MECHANISM OF INTESTINAL UTILIZATION OFMONOGLYCERIDES. Biochim Biophys Acta. 1964 Jun 15;84:264-74. PubMed PMID:14194232.

30: BROWN JL, JOHNSTON JM. DISTRIBUTION OF FATTY ACIDS IN TRIGLYCERIDESSYNTHESIZED FROM MONOGLYCERIDES. Biochim Biophys Acta. 1963 Oct22;70:603-5.PubMed PMID: 14085949.

EDUCATION

High School:Graduated from Magnet Cove High School, Magnet Cove AR 1953

University

North Texas State University, Denton, TX. B.S. degree in chemistry awarded 1958

Graduate SchoolNorth Texas State University, Denton, TX. M.S. degree in chemistry awarded 1959.

Thesis advisor - Price Truitt PhD.University of Texas Southwestern Medical School, Dallas TX. Ph.D. in biochemistryawarded 1964. Thesis advisor John M Johnston Ph.D. thesis title Role ofMonoglycerides in the Synthesis of Triglycerides in the Intestine.Post-Doctoral TrainingUniversity of California Los Angeles, Los Angeles CA in the laboratory of Irving ZabinPh.D. Worked on structural features of lac operon proteins.

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