Curriculum Vitae
James L. Thomas, Ph.D.
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Curriculum Vitae

Curriculum Vitae

James L. Thomas, Ph.D.

Professor of Pharmacology

Division of Basic Medical Sciences

Department of Obstetrics & Gynecology

 

 

Office Address          Division of Basic Medical Sciences

                                         Mercer University School of Medicine

                                         1550 College Street

                                         Macon, Georgia 31207

 

CONTACT                        478-301-4177 (office) 

                                         478-301-5326 (lab)   

                                         478-301-5489 (fax)

                                         Thomas_J@mercer.edu

                              

Education

               

Ph.D.  1981     University of Alabama at Birmingham (UAB)

                        Major: Pharmacology, Minor: Biochemistry

                        Advisor: Raymond H. Lindsay, Ph.D.

 

B.A.   1971      Emory University, Atlanta, GA

                        Major: Chemistry

 

POSTGRADUATE TRAINING

 

1996 -1997       Macromolecular Structure, Department of

                           Biochemistry, Washington University Graduate

                          Division of Biology and  Biomedical Sciences

                          (4.0 hr audit)

 

1993 – 1994      Laboratory on DNA Manipulation,

                           Department of Biology, Washington University

                           (4.0 hr credit)

 

1981 – 1985    Postdoctoral Research Associate

                         Department of Obstetrics & Gynecology

                         Washington University School of Medicine

                         St. Louis, Missouri

                         Mentor: Ronald C. Strickler, M.D.

 

FACULTY APPOINTMENTS

 

2010-present   Professor (with tenure)

                        Division of Basic Medical Sciences and

                        Department of Obstetrics and Gynecology

                        Mercer University School of Medicine

                        Macon, GA

 

2006- 2010     Associate Professor (with tenure)

                        Division of Basic Medical Sciences and

                        Department of Obstetrics and Gynecology

                        Mercer University School of Medicine

                        Macon, GA

 

2000 - 2005     Assistant Professor (tenure-track)

                        Division of Basic Medical Sciences and

                        Department of Obstetrics and Gynecology

                        Mercer University School of Medicine

                        Macon, GA

 

1991 – 2000    Research Assistant Professor 

                        Department of Obstetrics and Gynecology

                        Washington University School of Medicine

                        St. Louis, MO

                            

RESEARCH APPOINTMENTS

 

2010-present    Director of Summer Research Scholars

                         Mercer University School of Medicine

                         Macon, GA

 

2007-present    Director of Research Laboratories                        

                         Mercer University School of Medicine

                         Macon, GA

 

1985 – 1991    Research Instructor

                        Department of Obstetrics & Gynecology

                        Washington University School of Medicine

                         St. Louis, MO

 

1981 – 1985    Postdoctoral Research Associate

                        Department of Obstetrics & Gynecology

                        Washington University School of Medicine

                        St. Louis, Missouri                       

 

1972 – 1973    Electron microscopy technician

                        Department of Anatomy

                        Emory University School of Medicine

 

1966 – 1968    American Cancer Society Student Traineeship

Summers          Division of Endocrinology

                        University of Alabama School of Medicine

                        Mentor: James A. Pittman, Jr., M.D.
 
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 

Reviewer for the journals: Molecular and Cellular Endocrinology, Journal of Steroid Biochemistry and Molecular Biology,  Biochemistry, Journal of Endocrinology, Molecular Pharmacology, Archives of Biochemistry and Biophysics, Placenta, Epilepsia.

 

Reviewer of grant applications for the NIH Biochemical Endocrinology study section (Ad-hoc reviewer) and the March of Dimes.


Professional Societies

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

Research Support

Research Associate with Ronald C. Strickler, M.D., P.I. 
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 3-Hydroxysteroid
Dehydrogenase Isomerase", HD20055, 07/01/85 - 03/31/89,
$183,019 (direct costs).

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

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

Principal Investigator
National Institutes of Health, "Placental 3-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 3-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 3-Hydroxysteroid
Dehydrogenase Isomerase", CA114717, CA114717, 02/01/05 - 01/31/10,
$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.

Tutor in the Biomedical Problems Program (Phases: Human Development and Genetics, Renal (Coordinator), Endocrinology, 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.         Prasad M, Thomas JL, Whittal RM, Bose HS.  Mitochondrial 3-beta hydroxysteroid dehydrogenase enzyme activity requires a reversible pH-dependent conformational change at the intermembrane space. J Biol Chem 2012, 287, 9534-9546.

 

2.         Rajapaksha M, Thomas JL, Streeter M, Prasad M, Whittal RM,  Bell JD, Bose HS.  Lipid-mediated Unfolding of 3-beta hydroxysteroid dehydrogenase2 is essential for steroidogenic activity.  Biochemistry, 2012, 50, 11015−11024. 

 

3.         Pawlak KJ, Thomas JL, Prasad M, Whittal RM, Bose HS: Inner mitochondrial translocase Tim50 interacts with 3βHSD2 to regulate adrenal and gonadal steroidogenesis.  J Biol Chem, 2012, 286: 39130-39140.

 

4.         Conley AJ, Corbin CJ, Thomas JL, Gee N, Lasley BL, Moeller B, Stanley S, Berger T: Costs and consequences of cellular compartmentalization and competition among key enzymes involved in androgen and estrogen synthesis. Biol Reprod, 2012, 86: 1-8.

 

5.         Thomas JL, Bucholtz KM, Kacsoh B: Selective inhibition of human 3β-hydroxysteroid dehydrogenase type 1 as a potential treatment for breast cancer. J Steroid Biochem Molec Biol  2011, 125:57–65.   http://www.sciencedirect.com/science/article/pii/S0960076010003158

 

6.         Thomas JL, Mack VL, Sun J, Terrell JR, Bucholtz KM: The functions of key residues in the inhibitor, substrate and cofactor sites of human 3β-hydroxysteroid dehydrogenase type 1 are validated by mutagenesis. J Steroid Biochem Molec Biol 2010, 120:192-199. http://www.sciencedirect.com/science/article/pii/S0960076010002153

 

7.         Thomas JL, Bucholtz, KM , Sun J, Mack VL,  Kacsoh B: Structural basis for the selective inhibition of human 3β-hydroxysteroid dehydrogenase 1 in human breast tumor MCF-7 cells.  Mol Cell Endocrinol 2009, 302:174-182.

 

8.         Thomas JL, Mack VL, Glow JA, Moshkelani D, Terrell JR, Bucholtz KM:  Structure/function of the inhibition of human 3β-hydroxysteroid dehydrogenase type 1 and type 2 by trilostane. J Steroid Biochem Mol Biol 2008, 111: 66–73.

 

9.         Thomas JL, Huether R, Mack VL, Scaccia LA, Stoner RC, Duax WL:  Structure/function of human type 1 3β-hydroxysteroid dehydrogenase: an intrasubunit disulfide bond in the Rossmann-fold domain and a Cys residue in the active site are critical for substrate and coenzyme utilization. J Steroid Biochem Mol Biol 2007, 107:80-87.

 

10.         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 3-hydroxysteroid dehydrogenase/isomerase type 1. J Steroid Biochem Mol Biol 2006, 101:50-60.

 

11.       Duax WL, Thomas JL, Pletnev V, Addlagatta A, Huether R, Habegger L, Weeks CM: Determining structure and function of steroid dehydrogenase enzymes by sequence analysis, homology modeling and rational mutational analysis. Ann NY Acad Sci, 2005, 1061:135-148. DOI No. 10.1196/annals.1336.015.

 

12.       Thomas JL, Boswell EL, Scaccia LA, Pletnev V and Umland TC: Identification of key amino acids responsible for the substantially higher affinities of human type 1 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD1) for substrates, coenzymes and inhibitors relative to human 3β-HSD2. J Biol Chem, 2005, 280:21321-21328.

 

13.       Thomas JL, Umland TC, Scaccia LA, Boswell EL and Kacsoh B:  The higher affinity of human type 1 3β-hydroxysteroid dehydrogenase (3β-HSD1) for substrate and inhibitor steroids relative to human 3β-HSD2 is validated in MCF-7 tumor cells and related to subunit interactions.  Endocrine Res, 2004, 30:935-941.

 

14.       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.

 

15.       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.

 

16.       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.

 

17.       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.

 

18.       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.

 

19.       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.

 

Before arriving at Mercer University School of Medicine

 

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

 

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

 

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

 

23.       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) 3-hydroxysteroid dehydrogenase/isomerase.  J Steroid Biochem Molec Biol, 1998; 66:327-334.

 

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

 

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

 

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

 

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

 

28.       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 3-hydroxy-Δ5-steroid dehydrogenase/isomerase. J Soc Gynecol Invest 1994; 1:155-163.

 

29.       Thomas JL, Nash WE, Myers RP, Crankshaw MW, Strickler RC: Affinity radiolabeling identifies peptides and amino acids associated with substrate binding in human placental 3-hydroxy- Δ 5-steroid dehydrogenase.  J Biol Chem 1993; 268:18507-18512.

 

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

 

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

 

32.       Thomas JL, Strickler RC, Myers RP, Covey DF: Affinity labeling of human placental 3-hydroxy-Δ5-steroid dehydrogenase and steroid Δ-isomerase: evidence for bifunctional catalysis by a different conformation of the same protein for each enzyme activity.  Biochemistry 1992; 31:5522-5527.

 

33.       Thomas JL, Myers RP, Strickler RC: Analysis of coenzyme binding by human placental 3-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.

 

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

 

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

 

36.       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 3-hydroxy-5-ene steroid dehydrogenase.  Molec Endocrinol 1989; 3:1310-1312.

 

37.       Thomas JL, Myers RP, Strickler RC: Human placental 3-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.

 

38.       Thomas JL, Berko EA, Faustino A, Myers RP, Strickler RC: Human placental 3-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.

 

39.       Asibey-Berko E, Thomas JL, Strickler RC: A modified digitonin-precipitation radioassay for 3-hydroxy-Δ5-steroid dehydrogenase.  Anal Biochem 1987; 163:36-41.

 

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

 

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

 

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

 

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

 

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

 

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

 

46.       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.

 
Peer-reviewed abstracts: 65 (not shown)

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