Tatjana Abaffy

Positions:

Assistant Research Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2000

University of Auckland (New Zealand)

Grants:

Publications:

Functional analysis of a mammalian odorant receptor subfamily.

Phylogenetic analysis groups mammalian odorant receptors into two broad classes and numerous subfamilies. These subfamilies are proposed to reflect functional organization. Testing this idea requires an assay allowing detailed functional characterization of odorant receptors. Here we show that a variety of Class I and Class II mouse odorant receptors can be functionally expressed in Xenopus laevis oocytes. Receptor constructs included the N-terminal 20 residues of human rhodopsin and were co-expressed with Galphaolf and the cystic fibrosis transmembrane regulator to allow electrophysiological measurement of receptor responses. For most mouse odorant receptors tested, these conditions were sufficient for functional expression. Co-expression of accessory proteins was required to allow functional surface expression of some mouse odorant receptors. We used this assay to examine the receptive ranges of all members of the mouse odorant receptor 42 (MOR42) subfamily. MOR42-1 responded to dicarboxylic acids, preferring a 10-12 carbon chain length. MOR42-2 responded to monocarboxylic acids (7-10 carbons). MOR42-3 responded to dicarboxylic acids (8-10 carbons) and monocarboxylic acids (10-12 carbons). Thus, the receptive range of each receptor was unique. However, overlap between the individual receptive ranges suggests that the members of this subfamily form one contiguous subfamily receptive range, suggesting that odorant receptor subfamilies do constitute functional units.
Authors
Abaffy, T; Matsunami, H; Luetje, CW
MLA Citation
Abaffy, Tatjana, et al. “Functional analysis of a mammalian odorant receptor subfamily.J Neurochem, vol. 97, no. 5, June 2006, pp. 1506–18. Pubmed, doi:10.1111/j.1471-4159.2006.03859.x.
URI
https://scholars.duke.edu/individual/pub787145
PMID
16606354
Source
pubmed
Published In
Journal of Neurochemistry
Volume
97
Published Date
Start Page
1506
End Page
1518
DOI
10.1111/j.1471-4159.2006.03859.x

GSK3 involvement in amylin signaling in isolated rat soleus muscle.

Amylin can evoke insulin resistance by antagonizing insulin in a non-competitive manner. Here, we investigated the glycogenolytic effect of amylin in isolated skeletal muscle and compared it to the effects of a calcitonin gene-related peptide (CGRP). Amylin alone had no statistically significant effect on glucose transport. However, amylin decreased insulin-stimulated glucose transport by about 30%. The involvement of cAMP could not be detected at the concentrations shown to promote glycogenolysis. Previously, it has been shown that increased glycogen synthase kinase 3 (GSK3) activity plays a role in insulin resistance. Here, the ratio of GSK3 alpha:beta isoforms in rat soleus was found to be 1.2:1. We found that amylin increased GSK3alpha activity, which in turn led to increased phosphorylation of glycogen synthase and decreased glycogen synthesis de novo.
Authors
Abaffy, T; Cooper, GJS
MLA Citation
Abaffy, Tatjana, and Garth J. S. Cooper. “GSK3 involvement in amylin signaling in isolated rat soleus muscle.Peptides, vol. 25, no. 12, Dec. 2004, pp. 2119–25. Pubmed, doi:10.1016/j.peptides.2004.08.016.
URI
https://scholars.duke.edu/individual/pub1120539
PMID
15572200
Source
pubmed
Published In
Peptides
Volume
25
Published Date
Start Page
2119
End Page
2125
DOI
10.1016/j.peptides.2004.08.016

Adenylyl cyclase expression and modulation of cAMP in rat taste cells

cAMP is a second messenger implicated in sensory transduction for taste. The identity of adenylyl cyclase (AC) in taste cells has not been explored. We have employed RT-PCR to identify the AC isoforms present in taste cells and found that AC 4, 6, and 8 are expressed as mRNAs in taste tissue. These proteins are also expressed in a subset of taste cells as revealed by immunohistochemistry. Alterations of cAMP concentrations are associated with transduction of taste stimuli of several classes. The involvement of particular ACs in this modulation has not been investigated. We demonstrate that glutamate, which is a potent stimulus eliciting a taste quality termed umami, causes a decrease in cAMP in forskolin-treated taste cells. The potentiation of this response by inosine monophosphate, the lack of response to D-glutamate, and the lack of response to umami stimuli in nonsensory lingual epithelium all suggest that the cAMP modulation represents umami taste transduction. Because cAMP downregulation via ACs can be mediated through Gαi proteins, we examined the colocalization of the detected ACs with Gαi proteins and found that 66% of AC8 immunopositive taste cells are also positive for gustducin, a taste-specific Gαi protein. Whether AC8 is directly involved in signal transduction of umami taste remains to be established.
Authors
Abaffy, T; Trubey, KR; Chaudhari, N
MLA Citation
Abaffy, T., et al. “Adenylyl cyclase expression and modulation of cAMP in rat taste cells.” American Journal of Physiology  Cell Physiology, vol. 284, no. 6 53-6, June 2003.
URI
https://scholars.duke.edu/individual/pub1120543
Source
scopus
Published In
American Journal of Physiology. Cell Physiology
Volume
284
Published Date

Troponin T and serum enzymes in monitoring open heart surgery

The values of Troponin T (TnT), a structurally bound protein found in striated muscle cells, and of a group of enzymes were investigated as diagnostic criteria for acute myocardial infarction (AMI) following open heart surgery. In 16 patients subjected to open heart surgery, peripheral venous blood was collected over 5-70 h after surgery. TnT was measured by an enzyme immunoassay (Elisa, Boehringer Mannheim), CK-MB by the immunoinhibition method (Boehringer Mannheim), and total CK, LDH and AST were measured by standard spectrophotometric methods (Herbos, Sisak). The values of CK, LDH and AST were significantly above the reference range (p<0.05) throughout the measurement, while the CK-MB values were rather inconsistent, sometimes significantly above and sometimes close to the upper reference limit. The TnT values were always slightly above the upper reference limit, but this increase was not statistically significant (p<0.05). Since the outcome of open heart surgery in the patients was good, the data suggest that the enzyme pattern, being a consequence of abundant enzyme release from the heart tissue and blood cells during the surgery itself, cannot be taken as a reliable diagnostic parameter for AIM. TnT, with its slight increase, could be used as a sensitive and reliable parameter in monitoring the outcome of open heart surgery.
Authors
Topic, E; Zovko, V; Abaffy, T; Barbaric, V; Rudez, I; Jelic, I
MLA Citation
Topic, E., et al. “Troponin T and serum enzymes in monitoring open heart surgery.” Acta Clinica Croatica, vol. 33, no. 1–2, Jan. 1994, pp. 77–85.
URI
https://scholars.duke.edu/individual/pub1120541
Source
scopus
Published In
Acta Clinica Croatica
Volume
33
Published Date
Start Page
77
End Page
85

A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.

Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this receptor. We detected that agonist 19-hydroxyandrostenedione, a product of the aromatase reaction, is endogenously produced upon receptor activation. We characterized the effects of receptor activation on metabolism using a prostate cancer cell line and demonstrated decreased intracellular anabolic signals and cell viability, induction of cell cycle arrest, and increased expression of neuronal markers. Furthermore, upregulation of neuron-specific enolase by agonist treatment was abolished in OR51E2-KO cells. The results of our study suggest that OR51E2 activation results in neuroendocrine trans-differentiation. These findings reveal a new role for OR51E2 and establish this G-protein coupled receptor as a novel therapeutic target in the treatment of prostate cancer.
Authors
Abaffy, T; Bain, JR; Muehlbauer, MJ; Spasojevic, I; Lodha, S; Bruguera, E; O'Neal, SK; Kim, SY; Matsunami, H
MLA Citation
URI
https://scholars.duke.edu/individual/pub1322180
PMID
29892571
Source
pubmed
Published In
Frontiers in Oncology
Volume
8
Published Date
Start Page
162
DOI
10.3389/fonc.2018.00162