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:

Biogenesis of olfactory G protein-coupled receptors

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Peripheral Odor Coding in Mammals

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Olfactory moding in mammals

Administered By
Molecular Genetics and Microbiology
Awarded By
University of Pennsylvania
Role
Principal Investigator
Start Date
End Date

Olfactory moding in mammals

Administered By
Molecular Genetics and Microbiology
Awarded By
University of Pennsylvania
Role
Principal Investigator
Start Date
End Date

Publications:

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

Discovery of novel ligands for mouse olfactory receptor MOR42-3 using an in silico screening approach and in vitro validation.

The ligands for many olfactory receptors remain largely unknown despite successful heterologous expression of these receptors. Understanding the molecular receptive range of olfactory receptors and deciphering the olfactory recognition code are hampered by the huge number of odorants and large number of olfactory receptors, as well as the complexity of their combinatorial coding. Here, we present an in silico screening approach to find additional ligands for a mouse olfactory receptor that allows improved definition of its molecular receptive range. A virtual library of 574 odorants was screened against a mouse olfactory receptor MOR42-3. We selected the top 20 candidate ligands using two different scoring functions. These 40 odorant candidate ligands were then tested in vitro using the Xenopus oocyte heterologous expression system and two-electrode voltage clamp electrophysiology. We experimentally confirmed 22 of these ligands. The candidate ligands were screened for both agonist and antagonist activity. In summary, we validated 19 agonists and 3 antagonists. Two of the newly identified antagonists were of low potency. Several previously known ligands (mono- and dicarboxylic acids) are also confirmed in this study. However, some of the newly identified ligands were structurally dissimilar compounds with various functional groups belonging to aldehydes, phenyls, alkenes, esters and ethers. The high positive predictive value of our in silico approach is promising. We believe that this approach can be used for initial deorphanization of olfactory receptors as well as for future comprehensive studies of molecular receptive range of olfactory receptors.
Authors
Bavan, S; Sherman, B; Luetje, CW; Abaffy, T
MLA Citation
Bavan, Selvan, et al. “Discovery of novel ligands for mouse olfactory receptor MOR42-3 using an in silico screening approach and in vitro validation..” Plos One, vol. 9, no. 3, 2014. Pubmed, doi:10.1371/journal.pone.0092064.
URI
https://scholars.duke.edu/individual/pub1120528
PMID
24637889
Source
pubmed
Published In
Plos One
Volume
9
Published Date
Start Page
e92064
DOI
10.1371/journal.pone.0092064

A non-invasive method for in vivo skin volatile compounds sampling.

The use of volatile organic compounds (VOCs) emanating from human skin presents great potential for skin disease diagnosis. These compounds are emitted at very low concentrations. Thus, the sampling preparation step needs to be implemented before gas chromatography-mass spectrometry (GC-MS) analysis. In this work, a simple, non-invasive headspace sampling method for volatile compounds emanating from human skin is presented, using thin film as the extraction phase format. The proposed method was evaluated in terms of reproducibility, membrane size, extraction mode and storage conditions. First, the in vial sampling showed an intra- and inter-membrane RSD% less than 9.8% and 8.2%, respectively, which demonstrated that this home-made skin volatiles sampling device was highly reproducible with regard to intra-, inter-membrane sampling. The in vivo sampling was influenced not only by the skin metabolic status, but also by environmental conditions. The developed sampling set-up (or "membrane sandwich") was used to compare two different modes of sampling: headspace and direct sampling. Results demonstrated that headspace sampling had significantly reduced background signal intensity, indicating minimized contamination from the skin surface. In addition, membrane storage conditions both before and after sampling were fully investigated. Membranes stored in dry ice for up to 72 h after collection were tested and showed no or minimal change in volatile profiles. This novel skin volatile compounds sampling approach coupled with gas chromatography-mass spectrometry (GC-MS) can achieve reproducible analysis. This technique was applied to identify the biomarkers of garlic intake and alcohol ingestion. Dimethyl sulphone, allyl methyl sulfide and allyl mercaptan, as metabolites of garlic intake, were detected. In addition, alcohol released from skin was also detected using our "membrane-sandwich" sampling. Using the same approach, we analyzed skin VOCs from upper back, forearm and back thigh regions of the body. Our results show that different body locations share a number of common compounds (27/99). The area with most compounds detected was the upper back skin region, where the density of sebaceous glands is the highest.
Authors
Jiang, R; Cudjoe, E; Bojko, B; Abaffy, T; Pawliszyn, J
MLA Citation
Jiang, Ruifen, et al. “A non-invasive method for in vivo skin volatile compounds sampling..” Anal Chim Acta, vol. 804, Dec. 2013, pp. 111–19. Pubmed, doi:10.1016/j.aca.2013.09.056.
URI
https://scholars.duke.edu/individual/pub1120529
PMID
24267071
Source
pubmed
Published In
Anal Chim Acta
Volume
804
Published Date
Start Page
111
End Page
119
DOI
10.1016/j.aca.2013.09.056

Comparative analysis of volatile metabolomics signals from melanoma and benign skin: a pilot study.

The analysis of volatile organic compounds (VOC) as biomarkers of cancer is both promising and challenging. In this pilot study, we used an untargeted approach to compare volatile metabolomic signatures of melanoma and matched control non-neoplastic skin from the same patient. VOC from fresh (non-fixed) biopsied tissue were collected using the headspace solid phase micro extraction method (HS SPME) and analyzed by gas chromatography and mass spectrometry (GCMS). We applied the XCMS analysis platform and MetaboAnalyst software to reveal many differentially expressed metabolic features. Our analysis revealed increased levels of lauric acid (C12:0) and palmitic acid (C16:0) in melanoma. The identity of these compounds was confirmed by comparison with chemical standards. Increased levels of these fatty acids are likely to be a consequence of up-regulated de novo lipid synthesis, a known characteristic of cancer. Increased oxidative stress is likely to cause an additional increase in lauric acid. Implementation of this study design on larger number of cases will be necessary for the future metabolomics biomarker discovery applications.
Authors
Abaffy, T; Möller, MG; Riemer, DD; Milikowski, C; DeFazio, RA
MLA Citation
Abaffy, T., et al. “Comparative analysis of volatile metabolomics signals from melanoma and benign skin: a pilot study..” Metabolomics, vol. 9, no. 5, 2013, pp. 998–1008. Pubmed, doi:10.1007/s11306-013-0523-z.
URI
https://scholars.duke.edu/individual/pub1120531
PMID
24039618
Source
pubmed
Published In
Metabolomics : Official Journal of the Metabolomic Society
Volume
9
Published Date
Start Page
998
End Page
1008
DOI
10.1007/s11306-013-0523-z

The location of olfactory receptors within olfactory epithelium is independent of odorant volatility and solubility.

BACKGROUND: Our objective was to study the pattern of olfactory receptor expression within the dorsal and ventral regions of the mouse olfactory epithelium. We hypothesized that olfactory receptors were distributed based on the chemical properties of their ligands: e.g. receptors for polar, hydrophilic and weakly volatile odorants would be present in the dorsal region of olfactory epithelium; while receptors for non-polar, more volatile odorants would be distributed to the ventral region. To test our hypothesis, we used micro-transplantation of cilia-enriched plasma membranes derived from dorsal or ventral regions of the olfactory epithelium into Xenopus oocytes for electrophysiological characterization against a panel of 100 odorants. FINDINGS: Odorants detected by ORs from the dorsal and ventral regions showed overlap in volatility and water solubility. We did not find evidence for a correlation between the solubility and volatility of odorants and the functional expression of olfactory receptors in the dorsal or ventral region of the olfactory epithelia. CONCLUSIONS: No simple clustering or relationship between chemical properties of odorants could be associated with the different regions of the olfactory epithelium. These results suggest that the location of ORs within the epithelium is not organized based on the physico-chemical properties of their ligands.
Authors
Abaffy, T; Defazio, AR
MLA Citation
Abaffy, Tatjana, and Anthony R. Defazio. “The location of olfactory receptors within olfactory epithelium is independent of odorant volatility and solubility..” Bmc Res Notes, vol. 4, May 2011. Pubmed, doi:10.1186/1756-0500-4-137.
URI
https://scholars.duke.edu/individual/pub1120535
PMID
21548958
Source
pubmed
Published In
Bmc Research Notes
Volume
4
Published Date
Start Page
137
DOI
10.1186/1756-0500-4-137