Faculty: Biography
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J. David Puett, Ph.D. Regents Professor Biochemistry and Molecular Biology
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| Biosketch | |||
|---|---|---|---|
| M.S. Physics | Univ. of North Carolina at Chapel Hill | Chapel Hill, NC | 1965 |
| Ph.D. Biochemistry | Univ. of North Carolina at Chapel Hill | Chapel Hill, NC | 1969 |
- Post-doctoral Experience
- Honors and Awards
- 2005 Honorary Professorship, Jilin University, Changchun, China
2001 Regents Professor, UGA
1977-79 Reproductive Biology Study Section (ad hoc), NIH
1982-87 Editorial Board, The Journal of Biological Chemistry
1983-86 Editorial Board, The Journal of Andrology
1979-82 Biochemical Endocrinology Study Section, NIH
1985-90 Scientific Advisory Board, Cancer Research Council, Bethesda, MD
1989-91 Scientific Advisory Board, Women’s Res. Inst., University of Kansas, Wichita, KS
1990 Consultant to the World Health Organization in China
1991-93 Chairperson, Biochemical Endocrinology Study Section, NIH (Member: 1990-93)
1993-present Editorial Board, Endocrine
1994-97 Member, Tumor Biochem. & Endocrin. Review Panel, American Cancer Society
1996-99 Editorial Board, Endocrinology
2003-07 Editorial Boards, Endocrine Reviews and Molecular Endocrinology
Honors
1971-76 Camille & Henry Dreyfus Teacher-Scholar Awardee of the Dreyfus Foundation
1975-80 Research Career Development Awardee of NIH
2005-President of the Association of Medical & Graduate Depts. Biochem.
- Research Interests
- Current research interests encompass several major
interrelated areas: (1) molecular and cellular biochemical endocrinology of
the glycoprotein hormones and their G protein-coupled receptors (GPCRs),
with particular emphasis on the gonadotropin, human chorionic gonadotropin
(hCG), and its receptor (LHR), (2) cancer biology and detection; and (3)
human embryonic stem cells. (1) Molecular and cellular biochemical
endocrinology: Research in this area represents a long-standing major focus
of the laboratory, beginning at the Vanderbilt University School of
Medicine, then at the University of Miami School of Medicine, and now at
the University of Georgia. Current research in this area is concentrated
on: (a) the family of homologous, heterodimeric glycoprotein hormones,
composed of a common a subunit and a hormone-specific b-subunit [LH
(luteinizing hormone), FSH (follicle-stimulating hormone), and TSH
(thyroid-stimulating hormone) from the anterior pituitary, and hCG from the
syncytiotrophoblast of the placenta]; (b) their cognate GPCRs, products of
one of the largest gene families in the human genome; and (c) the G
proteins activated by these receptors, notably Gs. These
ligand-receptor-downstream signaling systems regulate the reproductive axis
and basal metabolic rate in humans and other animals. The major goals of
this project are to elucidate structure-function relationships of the
ligands, receptors, and G proteins, including the molecular aspects of
ligand-receptor interaction, followed by transmembrane and intracellular
signaling leading to biological responses. The experimental approaches
include site-directed mutagenesis of the glycoprotein hormones and their
receptors, protein engineering, biophysical studies, molecular modeling,
and elucidation of cellular signaling pathways mediated by constitutively
active and ligand-activated gonadotropin receptors. (2) Cancer biology and
detection: Research in this area is focused on the use of hCG as an early
marker for cancer. It is well established that trophoblastic malignancies
and several other non-trophoblastic malignancies express hCG or one of its
subunits and that the pattern of glycosylation in hCG from transformed
cells differs from that of normal production by syncytiotrophoblasts. The
primary goals of this research area include the use of hyperglycosylated
hCG as a marker for the presence of cancer or response to treatment. A
variety of experimental approaches are used including characterization of
tumor cell-derived hCG, e.g. in established human tumor lines and in serum
and urine of cancer patients, with emphasis on detection of the aberrant
glycosylation. A new technology platform is under development that utilizes
capture of hCG by an appropriately modified antibody, followed by specific
lectin binding to probe the glycoforms present. Another cancer-related
project deals with the mechanism(s) by which hCG inhibits the growth of
cultured human ovarian and breast cancer cell lines. (3) Human embryonic
stem cells: A new area of research is developing using human embryonic stem
cells. Differentiation markers such as hCG and others are being explored to
ascertain the status of differentiation and cell linage.
- Representative Publications
- R.L. Schubert and D. Puett (2003) “Single-Chain Human Chorionic Gonadotropin Analogs Containing the Determinant Loop of the β-Subunit Linked to the α-Subunit,” J. Mol. Endocrinol. 31, 157-168.
T.P. Meehan, D. Puett, and P. Narayan (2004) “Tightly Regulated and Inducible Expression of a Yoked Hormone-Receptor Complex in HEK 293 Cells”, J. Mol. Endocrinol. 32, 247-255.
K. Angelova, V. Fremont, R. Jain, M. Zhang, D. Puett, P. Narayan, and M. Szkudlinski (2004) “Human -Subunit Analogs Act as Partial Agonists to the Thyroid-Stimulating Hormone Receptor: Differential Effects of Free and Yoked Subunits,” Endocrine 24, 25-31.
L.S. Kelly, M. Kozak, T. Walker, M. Pierce, and D. Puett (2005) “Lectin Immunoassays using Antibody Fragments to Human Chorionic Gonadotropin Secreted by Choriocarcinoma Cells, “Anal. Biochem. 338, 253-262.
T.P. Meehan, B.G. Harmon, M.E. Overcast, K.K. Yu, S.A. Camper, D. Puett, and P. Narayan (2005) “Gonadal Defects and Hormonal Alterations in Transgenic Mice Expressing a Single Chain Human Chorionic Gonadotropin - Lutropin Receptor Complex,” J. Mol. Endocrinol. 34, 489-503.