James L. Thomas, Ph.D.

Personal Information

Place of Birth: Atlanta, Georgia
Citizenship: USA
Marital Status: Married, two children

Office Address:

 

Division of Basic Medical Sciences
Mercer University School of Medicine
1550 College Street
Macon, Georgia 31207

Office: 478-301-4177
Lab: 478-301-5326
Fax: 478-301-5489
Email: Thomas_J@mercer.edu

Divisional web page with faculty link:
http://medicine.mercer.edu/search?bio=thomas_j@mercer.edu&bio_num=0

Home Address:

 

4668 Savage Creek Drive
Macon, Georgia 31210
Home telephone: 478-474-3696

Present Position:

Asssistant Professor
Division of Basic Medical Sciences and
Department of Obstetrics and Gynecology
Mercer University School of Medicine

Education

B.A. 1971      Emory University, Atlanta, GA
                      Major: Chemistry

Ph.D. 1981    University of Alabama at Birmingham (U.A.B.)
                      Major: Pharmacology. Minor: Biochemistry
                      Advisor: Raymond H. Lindsay, Ph.D.

1981 - 1985  Postdoctoral Research Associate
                      Department of Obstetrics & Gynecology 
                      Washington University Medical School
                      St. Louis, Missouri
                      Advisor: Ronald C. Strickler, M.D.

1993 - 1994   Laboratory on DNA Manipulation, Department of Biology
                     Washington University (4.0 hr credit)

1996 -1997   Macromolecular Structure, Department of Biochemistry, 
                    Washington University Graduate Division of Biology and
                     Biomedical Sciences (4.0 hr audit)

Academic and Technical Positions

1965 - 1968  American Cancer Society Student Traineeship Program.
                     Division of Endocrinology
                     University of Alabama School of Medicine
                     Supervisor: Dr. James A. Pittman, Jr.

1972 - 1973   Electron microscopy technician
                      Department of Anatomy 
                      Emory University School of Medicine
                      Supervisor: Dr. Norbert Jones

1974 - 1975   Chemistry instructor
                      Red Mountain High School 
                      Birmingham, Alabama

1981 - 1985   Postdoctoral Research Associate
                     Department of Obstetrics & Gynecology
                     Washington University Medical School

1985 - 1991  Research Instructor 
                     Department of Obstetrics & Gynecology
                     Washington University Medical School

 

1991 - 2000  Research Assistant Professor
                     Department of Obstetrics and Gynecology
                     Washington University Medical School

2000-           Assistant Professor (tenure-track)
                    Division of Basic Medical Sciences and
                    Department of Obstetrics and Gynecology 
                    Mercer University School of Medicine

Honors and Awards

Pi Alpha Chemical Honor Society, 1971, Emory University
Sigma Xi Student Research Competition winner, 1977, U.A.B.
Graduate Student Fellowship (competitive), 1978-81, U.A.B.

Directed the research of the of the Medical Association of Georgia
Resident Research Competition winner, 2003, Mercer Univ Sch Med.

Peer Review

Grant reviewer for the Biochemical Endocrinology (BCE) study section of
NIH (ad-hoc)  and the March of Dimes.

 

For the journals: Biochemistry, J. Endocrinology, Molecular Pharmacology, Placenta, Epilepsia.

Professional Societies

The Endocrine Society, Society for Gynecologic Investigation, American
Society for Pharmacology and Experimental Therapeutics, American Society
for Biochemistry and Molecular Biology.

Research Support

Research Associate with Ronald C. Strickler, M.D.
National Institutes of Health, "Hydroxysteroid Dehydrogenases
in Human Placental Cytosol", HD15903, 01/01/82 - 12/31/84,
$129,322 (direct costs).

Co-Investigator
National Institutes of Health, "Placental 3ß-Hydroxysteroid
Dehydrogenase Isomerase", HD20055, 07/01/85 - 03/31/89,
$183,019 (direct costs).

Co-Investigator
National Institutes of Health, "Placental 3ß-Hydroxysteroid
Dehydrogenase Isomerase", HD20055, 04/01/89 - 03/31/94,
$573,716 (direct costs).

Principal Investigator
National Institutes of Health, "Placental 3ß-Hydroxysteroid
Dehydrogenase Isomerase", HD20055, 12/01/94 - 11/30/99,
$348,181 (direct costs).

Principal Investigator
National Institutes of Health, "Placental 3ß-Hydroxysteroid
Dehydrogenase Isomerase", HD20055, 03/01/00 - 02/28/05,
$540,000 (direct costs); $717,625 total costs awarded to Mercer University
on 08/01/00.

Principal Investigator
Medical Center of Central Georgia, Clinical Research Center
Inhibition of Human Type 1 3ß-Hydroxysteroid Dehydrogenase
Slows the Growth of Hormone-Sensitive Tumors. 07/01/02 -
6/30/03, $10,000 (direct costs).

Principal Investigator
MedCen Community Health Foundation Grant
Human type 1 placental 3B-hydroxysteroid dehydrogenase can be inhibited without affecting the activity of human type 2 adrenal 3B-HSD2.
10/01/03-09/30/04, $18,000 (direct costs).

Principal Investigator
National Institutes of Health, "Placental 3ß-Hydroxysteroid
Dehydrogenase Isomerase", CA114717, CA114717, 02/01/05 - 01/31/09,
$630,00 (direct costs); $928,052 total costs awarded to Mercer University.

Teaching

Selected lectures (antithyroid drugs, antipsychotic agents)
in the Pharmacology course at the University of Alabama at
Birmingham Medical, Dental, and Optometry Schools, 1977-80.

Directed the research of a graduate student in the
Washington University Graduate Division of Biology and
Biomedical Sciences, summer term, 1992.

Tutor in the Biomedical Problems Program (Phases: Human Development and
Genetics, Renal, Hematology).
Resource faculty for Pharmacology (Cancer chemotherapy, antimicrobials),
Direct the research of medical students and Ob-Gyn residents,
Mercer University School of Medicine, 2000 - present.

Published Articles

1. Pittman JA Jr, Thomas JL, Dale RC, Dailey G, Beschi RJ, Kontzen FN: Thyroidal radioiodine uptake values in euthyroid subjects in Birmingham, Alabama. Ala J Med Sci 1969; 6:46-51.

2. Thomas JL, Strickler RC: Human placental 17ß-estradiol dehydrogenase and 20a-hydroxysteroid dehydrogenase: studies with 6ß-bromoacetoxy-progesterone. J Biol Chem 1983; 258:1587-1590.

3. Thomas JL, LaRochelle MC, Covey DF, Strickler RC: Inactivation of human placental 17ß,20a-hydroxysteroid dehydrogenase by 16-methylene estrone, an affinity alkylator enzymatically generated from 16-methylene estradiol-17ß. J Biol Chem 1983; 258:11500-11504.

4. LaRochelle MC, Thomas JL, Strickler RC: Reactivation of human placental 17ß,20a-hydroxysteroid dehydrogenase: affirmation of affinity labeling principles. Steroids 1984; 43:209-217.

5. Thomas JL, LaRochelle MC, Asibey-Berko E, Strickler RC: Reactivation of human placental 17ß,20a-hydroxysteroid dehydrogenase affinity alkylated by estrone 3-bromoacetate: topographic studies with 16a-bromoacetoxy-estradiol-17ß 3-methyl ether. Biochemistry 1985; 24:5361-5367.

6. Thomas JL, Asibey-Berko E, Strickler RC: The affinity alkylators, 11a-bromoacetoxy-progesterone and estrone 3-bromoacetate, modify a common histidyl residue in the active site of human placental 17ß,20a-hydroxysteroid dehydrogenase. J Steroid Biochem 1986; 25:103-108.

7. Asibey-Berko E, Thomas JL, Strickler RC: 3ß-Hydroxysteroid dehydrogenase in human placental microsomes and mitochondria: co-solubilization of androstene and pregnene activities. Steroids 1986; 47:351-363.

8. Asibey-Berko E, Thomas JL, Strickler RC: A modified digitonin-precipitation radioassay for 3ß-hydroxysteroid dehydrogenase. Anal Biochem 1987; 163:36-41.

9. Thomas JL, Berko EA, Faustino A, Myers RP, Strickler RC: Human placental 3ß-hydroxy-5-ene-steroid dehydrogenase and steroid 5-4-ene-isomerase: purification from microsomes, substrate kinetics, and inhibition by product steroids. J Steroid Biochem 1988; 31:785-793.

10. Thomas JL, Myers RP, Strickler RC: Human placental 3ß-hydroxy-5-ene-steroid dehydrogenase and steroid 5-4-ene-isomerase: purification from mitochondria and kinetic profiles, biophysical characterization of the purified mitochondrial and microsomal enzymes. J Steroid Biochem 1989; 33:209-217.

11. Luu-The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F: Full length cDNA structure and deduced amino acid sequence of human 3ß-hydroxy-5-ene steroid dehydrogenase. Molec Endocrinol 1989; 3:1310-1312.

12. Doody KM, Carr BR, Rainey WE, Byrd W, Murry BA, Strickler RC, Thomas JL, Mason JI: 3ß-Hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland. Endocrinology 1990; 126:2487-2492.

13. Thomas JL, Myers RP, Rosik LO, Strickler RC: Affinity alkylation of human placental 3ß-hydroxy-5-ene-steroid dehydrogenase and steroid 5-4-ene-isomerase by 2a-bromoacetoxyprogesterone: evidence for separate dehydrogenase and isomerase sites on one protein. J Steroid Biochem 1990; 36:117-123.

14. Thomas JL, Myers RP, Strickler RC: Analysis of coenzyme binding by human placental 3ß-hydroxy-5-ene-steroid dehydrogenase and steroid 5-4-ene-isomerase using 5'-[p-(fluorosulfonyl)benzoyl]adenosine, an affinity labeling cofactor analog. J Steroid Biochem Molec Biol 1991; 39:471-477.

15. Thomas JL, Strickler RC, Myers RP, Covey DF: Affinity labeling of human placental 3ß-hydroxysteroid dehydrogenase and steroid 5-isomerase: evidence for bifunctional catalysis by a different conformation of the same protein for each enzyme activity. Biochemistry 1992; 31:5522-5527.

16. Strickler RC, Thomas JL: Affinity labeling identifies histidine at the active site of human placental 3ß-hydroxysteroid dehydrogenase/steroid 5-4-ene-isomerase. Am J Obstet Gynecol 1993; 168:1216-1222.

17. Milewich L, Shaw CE, Mason JI, Carr BR, Blomquist CH, Thomas JL: 3ß-Hydroxysteroid dehydrogenase activity in the tissues of human fetus determined with 5a-androstane-3ß,17ß-diol and dehydroepiandrosterone as substrates. J Steroid Biochem Molec Biol 1993; 45:525-537.

18. Thomas JL, Nash WE, Myers RP, Crankshaw MW, Strickler RC: Affinity radiolabeling identifies peptides and amino acids associated with substrate binding in human placental 3ß-hydroxysteroid dehydrogenase. J Biol Chem 1993; 268:18507-18512.

19. Thomas JL, Nash WE, Crankshaw MW, Strickler RC: Affinity labeling in the presence of the reduced diphosphopyridine nucleotide, NADH, identifies peptides associated with the activities of human placental 3ß-hydroxysteroid dehydrogenase/isomerase. J Soc Gynecol Invest 1994; 1:155-163.

20. Nash WE, Mercer RW, Blanco G, Strickler RC, Mason JI, Thomas JL: Over-expression of human type I (placental) 3ß-hydroxy-5-ene-steroid dehydrogenase/isomerase in insect cells infected with recombinant baculovirus. J Steroid Biochem Molec Biol 1994; 50:235-240.

21. Thomas JL, Frieden C, Nash WE, Strickler RC: An NADH-induced conformational change that mediates the sequential 3ß-hydroxysteroid dehydrogenase/isomerase activities is supported by affinity labeling and the time-dependent activation of isomerase. J Biol Chem 1995; 270:21003-21008.

22. Thomas JL, Nash WE, Strickler RC: Physiologic 3ß-hydroxy-5-ene-steroid substrates bind to 3ß-hydroxysteroid dehydrogenase without the prior binding of cofactor. J Steroid Biochem Molec Biol 1996; 58:211-216.

23. Thomas JL, Evans BW, Strickler RC: Affinity radiolabeling identifies peptides associated with the isomerase site in human type I (placental) 3ß-hydroxysteroid dehydrogenase/isomerase. Biochemistry 1997; 36:9029-9034.

 
24. Thomas JL, Evans BW, Blanco G, Mercer RW, Mason JI, Adler S, Nash WE, Isenberg KE, Strickler RC: Site-directed mutagenesis identifies amino acid residues associated with the dehydrogenase and isomerase activities of human type I (placental) 3ß-hydroxysteroid dehydrogenase/isomerase. J Steroid Biochem Molec Biol, 1998; 66:327-334.

25. Mason JI, Naville D, Evans BW, Thomas JL: Functional activity of 3ß-hydroxysteroid dehydrogenase/isomerase. Endocrine Res, 1998; 24:549-557.

26. Thomas JL, Evans BW, Blanco G, Mason JI, Strickler RC: Creation of a fully active, cytosolic form of human type I 3ß-hydroxysteroid dehydrogenase/isomerase by the deletion of a membrane-spanning domain. J Mol Endocrinol, 1999; 23:231-239.

27. Mason JI, Gordon-Walker TT, Zhang L, Pang S, Evans BW, Thomas JL: Structural-functional aspects of 3ß-hydroxysteroid dehydrogenase. Molecular Steroidogenesis, pp. 157-160, edited by M. Okamoto, Y. Ishimura, H. Nawata. Universal Academy Press, Tokyo, 2000.

28. Thomas JL, Mason JI, Blanco G, Veisaga ML: The engineered, cytosolic form of human type I 3β-hydroxysteroid dehydrogenase/isomerase: purification, characterization and crystallization. J Mol Endocrinol, 2001; 27:77-83.

29. Thomas JL, Mason JI, Brandt S, Spencer, BR, Norris W:  Structure/function relationships responsible for the kinetic differences between human type 1 and type 2 3β-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity.  J Biol Chem, 2002; 277:42795-42801.

30. Thomas JL, Mason JI, Brandt S, Norris W: Differences in Substrate and Inhibitor Kinetics of Human Type 1 and Type 2 3β-Hydroxysteroid Dehydrogenase (3β-HSD) are explained by the Type 1 Mutant, H156Y.  Endocrine Res, 2002; 28:475-479.

31. Thomas JL, Duax WL, Addlagatta A, Brandt S, Fuller R R, Norris W: Structure/function relationships responsible for coenzyme specificity and the isomerase activity of human type 1 3β-hydroxysteroid dehydrogenase/isomerase.  J Biol Chem, 2003; 37:35483-35490.

32. Thomas JL, Duax WL, Addlagatta A, Kacsoh B, Brandt S, Norris W: Structure/function aspects of human 3β-hydroxysteroid dehydrogenase. Mol Cell Endocrinol, 2004; 215:73-82.

33. Thomas JL, Duax WL, Addlagatta A, Scaccia L, KA Frizzell, Carloni SB:  Serine 124 completes the Tyr, Lys and Ser triad responsible for the catalysis of human type 1 3β-hydroxysteroid dehydrogenase.  J Mol Endocrinol, 2004, 33:253-261.

 

37.  Pletnev VZ, Thomas JL, Rhaney FL, Holt LS, Scaccia LA, Umland TC and Duax WL: Rational Proteomics V: Structure-based mutagenesis has revealed key residues responsible for substrate recognition and catalysis by the dehydrogenase and isomerase activities in human 3b-hydroxysteroid dehydrogenase/isomerase type 1. Proteins: Structure, Function and Bioinformatics 2005, submitted.

38. Thomas JL, Kacsoh B: The effect of regulated expression of transgenic human type 1 and type 2 3B-hydroxysteroid dehydrogenase on the dehydroepiandrosterone-induced proliferation of MCF-7 human breast cancer cells. In preparation.

Presentations

I have presented 56 posters and talks at scientific meetings during my research career. The invited and award-winning presentations are listed below.

30. Thomas JL, Nash WE, Strickler RC: Affinity radiolabeling with 5,10-secoestr-4-yne-3,10,17-trione identifies the isomerase site in human type I (placental) 3ß-hydroxysteroid dehydrogenase/isomerase. 2nd International Symposium on Molecular Steroidogenesis, Monterey, CA, June, 1996 (invited).

35. Mason JI, Naville D, Evans BW, Thomas JL: Functional activity of 3ß-hydroxysteroid dehydrogenase/isomerase. Eighth Adrenal Cortex Conference, Orford, Quebec, June, 1998 (invited).

37. Mason JI, Zhang L, Pang S, Evans BW, Thomas JL: 3beta-Hydroxysteroid dehydrogenase. 3rd International Symposium on Molecular Steroidogenesis, Nara, Japan, August, 1999 (invited).

42. Fuller RR, Norris W, Brandt B, Thomas JL: Structure/function Relationships Responsible for the Differences in Substrate and Inhibitor Kinetics of the Human 3-beta-hydroxysteroid Dehydrogenase/Isomerase Type 1 and 2 Isoforms May Allow the Tissue-Specific Inhibition of the Enzyme. Winner of the Bibb County Medical Society 2002-2003 Resident Research Award competition and of the Milford B. Hatcher Resident Research Award, awarded annually by the Medical Association of Georgia and MAG Mutual.

43. Thomas JL: Structure/function aspects of human 3beta-hydroxysteroid dehydrogenase. Serono Foundation Workshop on Molecular Steroidogenesis, Bath, UK, April, 2003. This symposium was the fourth in a series of international conferences held on molecular steroidogenesis every three or four years (invited symposium lecture).

44. Thomas JL: Structure/function of human 3beta-hydroxysteroid dehydrogenase and potential clinical applications. Hauptman-Woodward Medical Research Institute, Buffalo, NY, March, 2004.

45. Rhaney FL, Scaccia LA, Thomas JL: Structure/function relationships responsible for the binding of the substrate steroid for the human 3beta-hydroxysteroid dehydrogenase/isomerase that may lead to the tissue-specific inhibition of the enzyme in placenta and breast tumors. Third Place Winner of the Bibb County Medical Society 2002-2003 Resident Research Award competition


Recent abstracts:

51. Thomas JL, Strickler RC, Brandt S, Fuller R, Norris W:  Structure/Function relationships of substrate utilization by human type 1 (placental) 3β-hydroxysteroid dehydrogenase/Isomerase are characterized by site-directed mutagenesis. Society for Gynecologic Investigation, Abstract 640, Washington DC, March, 2003.

 

52. Thomas JL, Kacsoh B: Human type 1 3β-hydroxysteroid dehydrogenase (3β-HSD1) and 3β-HSD2 in genetically engineered MCF-7 human breast cancer cells exhibit substantial differences in DHEA substrate utilization and inhibition by epostane in both kinetic and cell proliferation studies. Abstract No. P3-301. Endocrine Society, New Orleans, LA, June, 2004.

 

53. Thomas JL, Duax WL, Scaccia LA, Frizzell KA and Carloni SB: Homology modeling and mutagenesis indicate that Serine 124 is a member of the Tyr/Lys/Ser triad responsible for the catalysis of human type 1 3β-hydroxysteroid dehydrogenase. Abstract No. P3-287. Endocrine Society, New Orleans, LA, June 2004.

 

54. Kacsoh B, Thomas JL: Intracrine mechanisms underlying dehydroepiandrosterone- (DHEA-) induced proliferation of MCF-7 human breast cancer cells.  Abstract No. P1-273.  Endocrine Society, New Orleans, LA, June, 2004.

 

55. Thomas JL, Scaccia LA, Boswell EL and Kacsoh B: Key differences in isoenzyme structure are responsible for the higher affinities of human type 1 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD1) for substrates and inhibitors relative to human 3β-HSD2 to characterize a new target enzyme for the treatment of breast cancer.  Keystone Symposium, Hormonal Regulation of Tumorigenesis, Monterey, CA, February, 2005.

 

56. Thomas JL, Rhaney FL, Scaccia LA, Umland TC: Identification of structure/function relationships responsible for the binding of the substrate steroid for human 3β-hydroxysteroid dehydrogenase/isomerase. Abstract No. P1-348.  Endocrine Society, San Diego, CA, June 2005.