Curriculum Vita for Jerry L Brown PhD

CONTACT INFORMATION
Name Jerry L Brown
Address 1020 Chaplin Ave, Lehigh Acres, FL 33971
Telephone (239) 491 0822
Cell Phone (501) 276 2296
Email jbrown7125@comcast.net

PERSONAL INFORMATION
Place of Birth Magnet Cove, AR
Citizenship US
Sex Male
Marital Status married
Spouse's Name Veronika
Children 1 adult son, Jason

EMPLOYMENT HISTORY
University of Colorado Health Sciences Center
Biochemistry and Molecular Genetics Department
13001 E 17th Place
Aurora, Colorado

I joined the faculty of the University of Colorado Medical School, Department of

Biochemistry as an Assistant Professor in August of 1967. I remained with this
institution until my retirement, June 30, 1999. During this time I rose through the
ranks to Associate Professor and then Professor, the department name was changed
twice, first to Biochemistry, Biophysics and Genetics and eventually to Biochemistry
and Molecular Genetics, I taught thousands of students in various courses (some of
these I directed) dealing with biochemistry and molecular biology. The student
population that I taught came largely from the medical, dental, and graduate
schools 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 molecular
biology.

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

Research

While at the University of Colorado my research was funded by grants that I

obtained from the NIH and the NSF. Due to my three moves after retiring I no
longer have specific information about these grants but during my 32 years at the
University of Colorado I raised several million dollars in research funds, which was
adequate to support my laboratory and research efforts.
My research interests evolved as my career progressed. I initially studied protein
structure and function which involved limited structural studies on terminal residues
of populations of proteins. I was interested in common structural features of
proteins and the roles these features may play (stability, localization, turnover rate
etc.) in the scheme of the organism. Perhaps the most significant finding from
these efforts was the observation that the amino terminal amino acids of most
soluble eukaryotic proteins are posttranslationally modified by α -N-acetylation. We
were unable to identify the purpose of this modification but did rule out some of the
more obvious possibilities. To my knowledge, the function(s) of this modification
remains unknown.
As these studies progressed I developed an interest in a human genetic disease, α -
1- proteinase inhibitor deficiency, caused by the impaired secretion variants of this
protein. Individuals expressing a poorly secreted variant of α -1- proteinase
inhibitor (A1Pi) are prone to develop pulmonary and/or liver problems as a result of
increased destruction of these tissues due to their inability to adequately inhibit
normal circulating serine proteinases. In an attempt to identify the cause of the
defective secretion of the variant proteins we constructed variants of the inhibitor
by oligonucleotide-directed mutagenesis of the cDNA specifying the most common
normal variant (A1PiM). These variants were expressed in COS cells and the
secretion of the variant forms compared to the secretion of A1Pi M. At the time we
began 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 bridge
between Lys 342 and Glu 290. Our results clearly demonstrated that this salt
bridge was not necessary for the efficient secretion of A1Pi. Our experiments also
showed that A1PiZ had a greatly enhanced propensity for aggregation. Large
inclusion bodies containing this protein formed in cells expressing this variant. It
seems likely that the defective secretion of is related to the aggregation of this
protein. 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 and
provided an alternate explanation for the secretion defect. We also constructed
some of the more rare variants of A1Pi that had been reported to be associated with
pulmonary disease and were in the process of characterizing these variants at the
time of my retirement

PUBLICATIONS

1: Ray S, Mickleborough TD, Brown JL. Comparison of the properties of rare

variants of alpha1-proteinase inhibitor expressed in COS-1 cells and assessment
of 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 highly
conserved sequence in the carboxyl-terminal region of members of the serpin
family in the secretion of alpha 1-proteinase inhibitor. J Biol Chem. 1994 Jun
24;269(25):17252-6. PubMed PMID: 8006033.

3: Leitinger B, Brown JL, Spiess M. Tagging secretory and membrane proteins with
a tyrosine sulfation site. Tyrosine sulfation precedes galactosylation and
sialylation in COS-7 cells. J Biol Chem. 1994 Mar 18;269(11):8115-21. PubMed
PMID: 8132536.

4: Samandari T, Brown JL. A study of the effects of altering the sites for
N-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 the
Glu264-Lys387 salt bridge on the secretion of alpha-1-proteinase inhibitor. J
Biol Chem. 1993 Mar 25;268(9):6771-6. PubMed PMID: 8454649.

6: Brodbeck RM, Brown JL. Secretion of alpha-1-proteinase inhibitor requires an

almost 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 the
effects 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 for

temperature-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 of
the Z variant of human alpha-1-proteinase inhibitor: secretion of variants having
altered 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 mutants
resulting 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 of
serum 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 immunoelectrophoresis

of
rat 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 and

nonacetylated 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

alpha-N-acylpeptide hydrolase from bovine liver. J Biol Chem. 1978 Jul
25;253(14):5012-8. PubMed PMID: 670173.

15: Maki RA, Brown JL, Cummings DJ. Transfer RNA methyltransferase activity in
paramecium aurelia. Biochim Biophys Acta. 1976 Mar 17;425(3):334-41. PubMed
PMID:
4103.

16: Brown JL, Roberts WK. Evidence that approximately eighty per cent of the
soluble proteins from Ehrlich ascites cells are N alpha-acetylated. J Biol Chem.
1976 Feb 25;251(4):1009-14. PubMed PMID: 1249063.

17: Prasad KN, Fogleman D, Gaschler M, Sinha PK, Brown JL. Cyclic
nucleotide-dependent protein kinase activity in malignant and cyclic AMP-induced
"differentiated" neuroblastoma cells in culture. Biochem Biophys Res Commun.
1976
Feb 23;68(4):1248-55. PubMed PMID: 178300.

18: Prasad KN, Sinha PK, Sahu SK, Brown JL. Binding of cyclic nucleotides with
soluble proteins increases in "differentiated" neuroblastoma cells in culture.
Biochem Biophys Res Commun. 1975 Sep 2;66(1):131-8. PubMed PMID: 169841.

19: Johnson GL, Brown JL. Partial purification and characterization of two
peptidases from Neurospora crassa. Biochim Biophys Acta. 1974 Dec
29;370(2):530-40. PubMed PMID: 4280316.

20: Brown JL. The modification of the amino terminal region of Escherichia coli
proteins after initiation with methionine analogues. Biochim Biophys Acta. 1973
Feb 4;294(1):527-9. PubMed PMID: 4574657.

21: Brown JL. Purification and properties of dipeptidase M from Escherichia coli
B. J Biol Chem. 1973 Jan 25;248(2):409-16. PubMed PMID: 4567782.

22: Brown JL, Krall JF. Studies on the substrate specificity of an Escherichia
coli peptidase. Biochem Biophys Res Commun. 1971 Feb 5;42(3):390-7. PubMed
PMID:
5542886.

23: Brown JL. The N-terminal region of soluble proteins from procaryotes and
eucaryotes. Biochim Biophys Acta. 1970 Dec 22;221(3):480-8. PubMed PMID:
5499431.

24: Brown JL, Koorjian S, Zabin I. Thiogalactoside transacetylase. Amino- and

carboxyl-terminal studies. J Biol Chem. 1967 Sep 25;242(18):4259-62. PubMed
PMID:
4863046.

25: Brown JL, Brown DM, Zabin I. Thiogalactoside transacetylase. Physical and
chemical studies of subunit structure. J Biol Chem. 1967 Sep 25;242(18):4254-8.
PubMed PMID: 4863045.

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

27: Brown JL, Koorajian S, Katze J, Zabin I. Beta-galactosidase. Amino-and

carboxyl-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 FOR
INTESTINAL TRIGLYCERIDE BIOSYNTHESIS. Biochim Biophys Acta. 1964 Aug
5;84:448-57.
PubMed PMID: 14230819.

29: BROWN JL, JOHNSTON JM. THE MECHANISM OF INTESTINAL UTILIZATION OF

MONOGLYCERIDES. Biochim Biophys Acta. 1964 Jun 15;84:264-74. PubMed PMID:
14194232.

30: BROWN JL, JOHNSTON JM. DISTRIBUTION OF FATTY ACIDS IN TRIGLYCERIDES

SYNTHESIZED FROM MONOGLYCERIDES. Biochim Biophys Acta. 1963 Oct
22;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 School
North 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 biochemistry
awarded 1964. Thesis advisor – John M Johnston Ph.D. – thesis title “Role of
Monoglycerides in the Synthesis of Triglycerides in the Intestine”.

Post-Doctoral Training
University of California Los Angeles, Los Angeles CA in the laboratory of Irving Zabin
Ph.D. Worked on structural features of lac operon proteins.