College of Agriculture & Natural Resources Reproductive and Developmental Sciences Training Program

Title

Co-Director Reproductive and Developmental Sciences NIH T32 Training Program, Co-Director Doctoral Student Recruitment and Retention Program (DSRRP), University Distinguished Professor, MSU Foundation Professor and Associate Chair for Research in the Department of Obstetrics, Gynecology & Reproductive Biology

Education

Asgi Fazleabas received his BS degree from California State University, Fresno and his PhD in Reproductive Physiology from the University of Illinois at Urbana-Champaign. Following his post-doctoral training in Reproductive Biology/Cell and Molecular Biology at the University of Florida in Gainesville he joined the Department of Obstetrics and Gynecology at the University of Illinois at Chicago where he held the rank of Professor and Director of the Center for Women\'s Health and Reproduction until October 2009. He is currently a Distinguished University Professor, MSU Foundation Professor and Associate Chair for Research in the Department of Obstetrics, Gynecology and Reproductive Biology and Director of the Center for Women\'s Health Research and Co-Director of the Reproductive and Developmental Sciences Program at Michigan State University.

Research Summary

Dr. Fazleabas has been funded continuously by the National Institutes of Health in the USA since 1986 for studies using the baboon as a model for reproductive biology research. The work in his laboratory has significant translational relevance related to improved pregnancy outcomes in infertile women as well as understanding the etiology and the pathophysiology associated with the development of endometriosis. A significant area of his research emphasis has been to study the early events associated with maternal-fetal interactions during the establishment of pregnancy and the mechanisms by which these interactions are affected in women and non-human primates with endometriosis. His laboratory was the first to demonstrate that endometrial responses to chorionic gonadotropin are attenuated in endometriosis as a consequence of progesterone resistance. In addition to studies in the non-human primate and in stromal cells from women, his laboratory has also developed novel transgenic models which have cell specific gain of function and loss of function properties to study the role of Notch signaling in endometriosis. Recent data from the laboratory suggests that the inflammatory cytokine IL-6 transcriptionally regulates NOTCH expression via the induction of E-Box proteins. In conjunction with the studies on the role of Notch signaling in the pathophysiology of endometriosis, his laboratory has developed a novel spheroid system that mimics the peritoneal environment in vitro and shown that these endometriotic organoids have a transcriptomic signature similar to spontaneous endometriotic lesions in the baboon. These transcriptomic analyses have also demonstrated that the baboon lesions have significant transcriptomic overlap with lesions obtained from adolescent women. Additional studies in his laboratory seek to identify similar genomic pathways that are associated with early lesion development in both baboons and adolescents with an emphasis targeted discovery and non-hormonal therapies. Other projects include the development of nanoparticles for targeted drug delivery as well as developing novel methodologies for the non-invasive diagnosis of endometriosis. He has over 250 peer reviewed publications and has authored multiple book chapters and reviews. The full list of publications is available at http://www.ncbi.nlm.nih.gov/pubmed/?term=Fazleabas.

Ongoing Research Support

1R01 HD 099090 (Fazleabas)                                                                       04/01/21-02/28/26
Regulation of Endometriotic Lesion Development by NOTCH1
This application focuses on the transcriptional regulation of NOTCH1 by E-Box Proteins in endometriotic lesions and its regulation by inflammatory cytokines – specifically IL-6

1R21HD114955 (Fazleabas)                                                                          08/01/24-07/31/26
Noninvasive and early detection of endometriosis using a biological neural circuit-based novel gas sensor.
The application uses a forward bioengineering approach to develop a non-invasive method to diagnose endometriosis by harnessing the power of an entire biological olfactory system and addition of biological neural computations to detect and distinguish Volatile Olfactory Compounds emitted by cell lines and urine from mice.

1 R01 HD 094842 (Missmer)                                                                          08/01/18-04/30/25            
What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment
This project focuses on genomic and transcriptomic analysis of the different clinical etiologies associated with endometriosis to identify differences in gene expression of the different clinical conditions. 

T32 HD087166 (Fazleabas/Latham)                                                              09/01/16-08/31/27                
Reproductive and Developmental Biology Training Program
Research into both animal and human reproductive biology has widespread implications for human health. This application proposes to establish a new Reproductive and Developmental Sciences Training Program (RDSTP) that will train young scientists to pursue research in High Program Priority Topic Areas identified by the NICHD/Fertility and Infertility (FI) Branch and the Gynecologic Health and Disease Branch. 

Recent Publications

1. Song, Y., G. W. Burns, N. R. Joshi, R. Arora, J. J. Kim and A. T. Fazleabas (2023). Spheroids as a model for endometriotic lesions. J.Clin Invest Insight 2023;8(11):e160815.https://doi.org/10.1172/jci.insight.160815. PMID: 37104033
2. Lacconi, V., M. Massimiani, D. Antonaci , C. Meneghini, F.G.Klinger , A.T. Fazleabas, H. Stuhlmann, R. Rago,  C. Ticconi  and L. Campagnolo (2023). Characterization of EGFL7 expression in normal endometrium and in the endometrium of women with poor reproductive outcomes. Molec Hum Reprod Hum Reprod. 38: 1345–1358. doi: 10.1093/humrep/dead086; PMID: 37159518
3. Kai, K., N. R. Joshi, G. W. Burns, S. M. Hrbek, E. L. Vegter, M. A. Ochoa-Bernal, Y. Song, G. E. Moldovan, L. F. Sempere, and A. T. Fazleabas (2023). MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis. Reprod Sci Reprod Sci. 30:2932-2944. doi: 10.1007/s43032-023-01253-5. PMID: 37188982
4. Xu, Qi-X., M. J. Madhavan, S-W. Wei, W-Q. Zhang, L. Lu, K-Z. Wang, Y. Zhao, H-T. Shao, J. Kang, A. T. Fazleabas, R. Arora, R-W. Su (2023). Aberrant activation of Notch1 signaling in the epithelium of the mouse uterus promotes hyperplasia by increasing estrogen sensitivity. FASEB J. 37 (7):e22983. https://doi.org/10.1096/fj.202201868RR. PMID: 37249327
5. Talebloo N., M. A. Ochoa Bernal, E. Kenyon, C. Mallet, A.T, Fazleabas and A. Moore (2023). Detection of endometriosis lesions using Gd-based collagen I targeting probe in murine models of endometriosis. Molec Imaging and Biol. 25:833-843. doi: 10.1007/s11307-023-01833-6. PMID: 37418136
6. Talebloo, N., M. A. Ochoa Bernal, E. Kenyon, C. Mallet, A.T. Fazleabas and A. Moore (2024). Imaging of endometriotic lesions using cRGD-MN probe in a mouse model of endometriosis. Nanomaterials E-Pub February 5th, 2024, 14: 319. doi: 10.3390/nano14030319. PMID: 38334590
7. Ochoa Bernal M.A. and A. T. Fazleabas (2024). The Known, the Unknown and the Future of the Pathophysiology of Endometriosis Int. J. Mol. Sci. 2024, 25(11), 5815; https://doi.org/10.3390/ijms25115815; PMID: 38892003
8. Burns G.W., Z. Fu, E.L. Vegter, Z.B. Madaj, E. Greaves, I. Flores and A.T. Fazleabas (2024). Spatial Transcriptomic Analysis Identifies Epithelium-Macrophage Crosstalk in Endometriotic Lesions. bioRxiv [Preprint]. 2024 May 14:2024.03.23.586434. doi: 10.1101/2024.03.23.586434. PMID: 38798560
9. Moldovan G.E., N. Massri, E. Vegter, I.L. Pauneto-Delgado, G.W. Burns, N. Joshi, B. Gu, R. Arora and A.T. Fazleabas (2024). Yes Associated Transcriptional Regulator 1 (YAP1) and WW Domain Containing Transcription Regulator (WWTR1) are required for murine pregnancy initiation. bioRxiv [Preprint]. 2024 May 10:2024.05.09.592984. doi:10.1101/2024.05.09.592984. PMID: 38766130 (Reproduction – In Press).
10. Ulrich N.D., A.Vargo, Q. Ma, Y.C.Shen, D.F. Hannum, S.J. Gurczynski, B.B. Moore, S. Schon, R. Lieberman, A. Shikanov, E.E. Marsh, A.T. Fazleabas, J.Z. Li and S.S. Hammoud (2024). Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women. Proc Natl Acad Sci Epub – October 29th 2024; DOI number 10.1073/pnas.2404775121. PMID: 38559249
11. Ochoa Bernal, M.A., Y. Song, N. Joshi, G.W. Burns, E. N. Paul, E. Vegter, S. Hrbek, L.F. Sempere, and A.T. Fazleabas (2024). The Regulation of MicroRNA-21 by Interleukin-6 and Its Role in the Development of Fibrosis in Endometriotic Lesions. Int J Mol Sci. Aug 19;25(16):8994. doi: 10.3390/ijms25168994. PMID: 39201680