Aristotelis Astreinidis

I am a biologist by training with more than 25 years of research experience in genetics, cell and molecular biology, biochemistry, and mouse models. I have a long-standing interest in and commitment to the study of pulmonary Lymphangioleiomyomatosis (LAM) and Tuberous Sclerosis Complex (TSC). I received my postdoctoral training in the laboratory of Dr. Elizabeth P. Henske, where we made seminal discoveries on the genetics, cell biology, and signaling pathways of LAM.

My research aims to identify drugs that target TSC1/TSC2-deficient cells and preferentially kill them, and to explore the underlying mechanisms leading to LAM. Following the observation that Wnt/b-catenin signaling is increased in rapamycin-insensitive cells, I am actively investigating the role of this pathway in LAM and TSC.

My main focus in the past 15 years is the mitotic functions of TSC1/TSC2: the regulation of mitotic progression by TSC1/TSC2 and mTORC, and the exploitation of these processes as therapeutic targets for TSC and LAM. I identified TSC1 as CDK1/cycling B1 substrate and an interacting partner of the mitotic kinase PLK1, discovered that the PI3K/mTOR signaling pathway interacts with a network of mitotic regulators, including PLK1, and shoed that PLK1 inhibition leads to preferential growth and survival inhibition and promotion of apoptosis in TSC-deficient cells, compared to controls.

Lately, we developed the first TSC2-deficient rapamycin-insensitive cell line which has enhanced tumorigenic properties, including expression of EMT markers and aberrant activation of Wnt/beta-catenin signaling. We are utilizing this and additional rapamycin-insensitive cell lines to delineate the molecular and gene expression changes associated with TSC2-null tumor survival during rapamycin treatment.

Throughout my career, I successfully applied for and administered research grants, collaborated with other investigators, and produced peer-reviewed publications from each project.

B.S.: Aristotle University of Thessaloniki Greece, 1993 (Biology)

Ph.D.: Aristotle University of Thessaloniki Greece, 1998 (Biology)

Lymphangioleiomyomatosis (LAM), Tuberous Sclerosis Complex (TSC), renal cancer, lung cancer, signal transduction, signaling pathway cross-talk, resistance to therapy, drug discovery

09-2002 -07-2005 Research Associate, Fox Chase Cancer Center, Philadelphia, PA

07-2005 -07-2007 Staff Scientist, Fox Chase Cancer Center, Philadelphia, PA

08-2007 -07-2012 Research Assistant Professor, Drexel University College of Medicine, Philadelphia, PA

08-2012 -05-2014 Assistant Professor, University of Ioannina School of Medicine, Greece

06-2014 -07-2016 Assistant Professor, Texas Tech University Health Sciences Center, Abilene, TX

2014 -2015 Member and Consultant, ExperImmune Center for Immunotherapeutic Development, Abilene, TX

2015 -2016 Co-director, Graduate School of Biomedical Sciences Biotechnology Program, Texas Tech University Health Sciences Center, Abilene, TX

08-2016 -07-2021 Assistant Professor, University of Tennessee Health Science Center, Memphis, TN

08-2021 -11-2023 Research Scientist, University of Cincinnati, Cincinnati, OH

Investigators:Aristotelis Astreinidis 2001 -2004 The LAM Foundation Cell Motility and Invasion in Tuberous Sclerosis and Lymphangioleiomyomatosis Role:PI Completed Type:Fellowship

Grant: #LAM058F07-06 Investigators:Aristotelis Astreinidis 2006 -2009 The LAM Foundation Role of the hamartin-Plk1 interaction in the pathogenesis of pulmonary lymphangioleiomyomatosis Role:PI Completed Type:Grant

Investigators:Aristotelis Astreinidis 2009 -2012 Department of Defense Role of the hamartin-Plk1 interaction in Tuberous Sclerosis Complex Pathogenesis Role:PI Completed Type:Grant

Investigators:Aristotelis Astreinidis 2010 -2012 Tuberous Sclerosis Alliance Screen of FDA-approved drugs as a therapeutic approach for Tuberous Sclerosis Complex Role:PI Completed Type:Grant

Investigators:Aristotelis Astreinidis 2015 -2015 Orphan Disease Center University of Pennsylvania Evaluation of PLK1 inhibitors in a pre-clinical LAM animal model Role:PI Completed Type:Grant

Investigators:Aristotelis Astreinidis; John J. Bissler 2020 -2021 Willian and Ella Owens Medical Research Foundation Targeting epithelial-to-mesenchymal transition (EMT) associated with rapalog non-responsiveness Role:PI Completed Type:Grant

Grant: #R56DK137834 Investigators:Astreinidis, Aristotelis; Yu, Jane 09-20-2023 -09-19-2024 National Inst of Diabetes and Digestive and Kidney Disease Polo-like kinase 1 and sphingosine-1-phosphate circuitry enhances TSC-mutant cell survival Role:Collaborator 99999.00 Awarded Level:Federal

Peer Reviewed Publications

Lu, Yiyang; Liu, Xiaolei; Zhang, Erik; Kopras, Elizabeth J; Smith, Eric P; Astreinidis, Aristotelis; Li, Chenggang; Leung, Yuet-Kin; Ho, Shuk-Mei; Yu, Jane J (2020. ) Estrogen activates pyruvate kinase M2 and increases the growth of TSC2-deficient cells.PloS one, , 15 (2 ) ,e0228894 More Information

Kumar, Prashant; Zadjali, Fahad; Yao, Ying; Siroky, Brian; Astrinidis, Aristotelis; Gross, Kenneth W; Bissler, John J (2021. ) Tsc Gene Locus Disruption and Differences in Renal Epithelial Extracellular Vesicles.Frontiers in physiology, , 12 ,630933 More Information

Zadjali, Fahad; Kumar, Prashant; Yao, Ying; Johnson, Daniel; Astrinidis, Aristotelis; Vogel, Peter; Gross, Kenneth W; Bissler, John J (2020. ) Tuberous Sclerosis Complex Axis Controls Renal Extracellular Vesicle Production and Protein Content.International journal of molecular sciences, , 21 (5 ) , More Information

Cho, Jun-Hung; Patel, Bhaumik; Bonala, Santosh; Mansouri, Hossein; Manne, Sasikanth; Vadrevu, Surya Kumari; Ghouse, Shanawaz; Kung, Che-Pei; Murphy, Maureen E; Astrinidis, Aristotelis; Henske, Elizabeth P; Kwiatkowski, David J; Markiewski, Maciej M; Karbowniczek, Magdalena (2019. ) The Codon 72 TP53 Polymorphism Contributes to TSC Tumorigenesis through the Notch-Nodal Axis.Molecular cancer research : MCR, , 17 (8 ) ,1639-1651 More Information

Valianou, Matthildi; Filippidou, Natalia; Johnson, Daniel L; Vogel, Peter; Zhang, Erik Y; Liu, Xiaolei; Lu, Yiyang; Yu, Jane J; Bissler, John J; Astrinidis, Aristotelis (2019. ) Rapalog resistance is associated with mesenchymal-type changes in Tsc2-null cells.Scientific reports, , 9 (1 ) ,3015 More Information

Bissler, John J; Zadjali, Fahad; Bridges, Dave; Astrinidis, Aristotelis; Barone, Sharon; Yao, Ying; Redd, JeAnna R; Siroky, Brian J; Wang, Yanqing; Finley, Joel T; Rusiniak, Michael E; Baumann, Heinz; Zahedi, Kamyar; Gross, Kenneth W; Soleimani, Manoocher (2019. ) Tuberous sclerosis complex exhibits a new renal cystogenic mechanism.Physiological reports, , 7 (2 ) ,e13983 More Information

Avgeris, Socratis; Fostira, Florentia; Vagena, Andromachi; Ninios, Yiannis; Delimitsou, Angeliki; Vodicka, Radek; Vrtel, Radek; Youroukos, Sotirios; Stravopodis, Dimitrios J; Vlassi, Metaxia; Astrinidis, Aristotelis; Yannoukakos, Drakoulis; Voutsinas, Gerassimos E (2017. ) Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece.Scientific reports, , 7 (1 ) ,16697 More Information

Markiewski, Maciej M; Vadrevu, Surya Kumari; Sharma, Sharad K; Chintala, Navin Kumar; Ghouse, Shanawaz; Cho, Jun-Hung; Fairlie, David P; Paterson, Yvonne; Astrinidis, Aristotelis; Karbowniczek, Magdalena (2017. ) The Ribosomal Protein S19 Suppresses Antitumor Immune Responses via the Complement C5a Receptor 1.Journal of immunology (Baltimore, Md. : 1950), , 198 (7 ) ,2989-2999 More Information

Rajan, Robin; Karbowniczek, Magdalena; Pugsley, Haley R; Sabnani, Manoj K; Astrinidis, Aristotelis; La-Beck, Ninh M (2015. ) Quantifying autophagosomes and autolysosomes in cells using imaging flow cytometry.Cytometry. Part A : the journal of the International Society for Analytical Cytology, , 87 (5 ) ,451-8 More Information

Valianou, Matthildi; Cox, Andrew M; Pichette, Benjamin; Hartley, Shannon; Paladhi, Unmesha Roy; Astrinidis, Aristotelis (2015. ) Pharmacological inhibition of Polo-like kinase 1 (PLK1) by BI-2536 decreases the viability and survival of hamartin and tuberin deficient cells via induction of apoptosis and attenuation of autophagy.Cell cycle (Georgetown, Tex.), , 14 (3 ) ,399-407 More Information

Gómez-Baldó, Laia; Schmidt, Stephan; Maxwell, Christopher A; Bonifaci, Núria; Gabaldón, Toni; Vidalain, Pierre-Olivier; Senapedis, William; Kletke, Anja; Rosing, Mechthild; Barnekow, Angelika; Rottapel, Robert; Capellá, Gabriel; Vidal, Marc; Astrinidis, Aristotelis; Piekorz, Roland P; Pujana, Miguel Angel (2010. ) TACC3-TSC2 maintains nuclear envelope structure and controls cell division.Cell cycle (Georgetown, Tex.), , 9 (6 ) ,1143-55 More Information

Astrinidis, Aristotelis; Kim, Jiyoon; Kelly, Crystal M; Olofsson, Beatrix A; Torabi, Behzad; Sorokina, Elena M; Azizkhan-Clifford, Jane (2010. ) The transcription factor SP1 regulates centriole function and chromosomal stability through a functional interaction with the mammalian target of rapamycin/raptor complex.Genes, chromosomes & cancer, , 49 (3 ) ,282-97 More Information

Matthew, Elizabeth M; Hart, Lori S; Astrinidis, Aristotelis; Navaraj, Arunasalam; Dolloff, Nathan G; Dicker, David T; Henske, Elizabeth P; El-Deiry, Wafik S (2009. ) The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth and chemosensitivity under hypoxic conditions.Cell cycle (Georgetown, Tex.), , 8 (24 ) ,4168-75 More Information

Yu, Jane J; Robb, Victoria A; Morrison, Tasha A; Ariazi, Eric A; Karbowniczek, Magdalena; Astrinidis, Aristotelis; Wang, Chunrong; Hernandez-Cuebas, Lisa; Seeholzer, Laura F; Nicolas, Emmanuelle; Hensley, Harvey; Jordan, V Craig; Walker, Cheryl L; Henske, Elizabeth P (2009. ) Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells.Proceedings of the National Academy of Sciences of the United States of America, , 106 (8 ) ,2635-40 More Information

Robb, Victoria A; Astrinidis, Aristotelis; Henske, Elizabeth P (2006. ) Frequent [corrected] hyperphosphorylation of ribosomal protein S6 [corrected] in lymphangioleiomyomatosis-associated angiomyolipomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, , 19 (6 ) ,839-46 More Information

Astrinidis, Aristotelis; Senapedis, William; Henske, Elizabeth P (2006. ) Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner.Human molecular genetics, , 15 (2 ) ,287-97 More Information

Karbowniczek, Magdalena; Cash, Timothy; Cheung, Mitchell; Robertson, Gavin P; Astrinidis, Aristotelis; Henske, Elizabeth Petri (2004. ) Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent.The Journal of biological chemistry, , 279 (29 ) ,29930-7 More Information

Yu, Jane; Astrinidis, Aristotelis; Howard, Sharon; Henske, Elizabeth Petri (2004. ) Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways.American journal of physiology. Lung cellular and molecular physiology, , 286 (4 ) ,L694-700 More Information

Astrinidis, Aristotelis; Senapedis, William; Coleman, Thomas R; Henske, Elizabeth Petri (2003. ) Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B.The Journal of biological chemistry, , 278 (51 ) ,51372-9 More Information

Karbowniczek, Magdalena; Astrinidis, Aristotelis; Balsara, Binaifer R; Testa, Joseph R; Lium, James H; Colby, Thomas V; McCormack, Francis X; Henske, Elizabeth Petri (2003. ) Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism.American journal of respiratory and critical care medicine, , 167 (7 ) ,976-82 More Information

Astrinidis, Aristotelis; Cash, Timothy P; Hunter, Deborah S; Walker, Cheryl L; Chernoff, Jonathan; Henske, Elizabeth P (2002. ) Tuberin, the tuberous sclerosis complex 2 tumor suppressor gene product, regulates Rho activation, cell adhesion and migration.Oncogene, , 21 (55 ) ,8470-6 More Information

Khare, L; Astrinidis, A; Senapedis, W; Adams, P D; Henske, E Petri (2002. ) Expression of wild type and mutant TSC2, but not TSC1, causes an increase in the G1 fraction of the cell cycle in HEK293 cells.Journal of medical genetics, , 39 (9 ) ,676-80 More Information

Yu, J; Astrinidis, A; Henske, E P (2001. ) Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis.American journal of respiratory and critical care medicine, , 164 (8 Pt 1 ) ,1537-40 More Information

Carsillo, T; Astrinidis, A; Henske, E P (2000. ) Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.Proceedings of the National Academy of Sciences of the United States of America, , 97 (11 ) ,6085-90 More Information

Astrinidis, A; Khare, L; Carsillo, T; Smolarek, T; Au, K S; Northrup, H; Henske, E P (2000. ) Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis.Journal of medical genetics, , 37 (1 ) ,55-7 More Information

Ivanova, R; Astrinidis, A; Lepage, V; Djoulah, S; Wijnen, E; Vu-Trieu, A N; Hors, J; Charron, D (1999. ) Mitochondrial DNA polymorphism in the Vietnamese population.European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics, , 26 (6 ) ,417-22 More Information

Ivanova, R; Astrinidis, A; Djoulah, S; Lepage, V; Wijnen, E; Hors, J; Charron, D (1999. ) Mitochondrial DNA polymorphisms of a west Algerian population (Oran region).Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, , 53 (8 ) ,386-92 More Information

Ivanova, R; Astrinidis, A; Lepage, V; Kouvatsi, A; Djoulah, S; Hors, J; Charron, D (1999. ) Mitochondrial DNA polymorphism in the French population.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, , 53 (4 ) ,207-12 More Information

Valianou, M G; Kouvatsi, A; Hassapopoulou-Matamis, H; Astrinidis, A; Triantaphyllidis, C (1999. ) Heterogeneity of four beta-thalassemia mutations in Greece.Hemoglobin, , 23 (1 ) ,79-82 More Information

Astrinidis, A; Kouvatsi, A; Nahmias, J; Povey, S; Pandeliadis, C; Danzaki, A; Schneider, M; Triantaphyllidis, C (1998. ) Novel intragenic polymorphisms in the tuberous sclerosis 2 (TSC2) gene. Mutations in brief no. 184. Online. Human mutation, , 12 (3 ) ,217

Astrinidis, A; Kouvatsi, A (1994. ) Mitochondrial DNA polymorphism in northern Greece. Human biology, , 66 (4 ) ,601-11

Kumar, Prashant; Zadjali, Fahad; Yao, Ying; Johnson, Daniel; Siroky, Brian; Astrinidis, Aristotelis; Vogel, Peter; Gross, Kenneth W; Bissler, John J (2022. ) Tsc2 mutation induces renal tubular cell nonautonomous disease.Genes & diseases, , 9 (1 ) ,187-200 More Information

Olatoke, Tasnim; Wagner, Andrew; Astrinidis, Aristotelis; Zhang, Erik Y; Guo, Minzhe; Zhang, Alan G; Mattam, Ushodaya; Kopras, Elizabeth J; Gupta, Nishant; Smith, Eric P; Karbowniczek, Magdalena; Markiewski, Maciej M; Wikenheiser-Brokamp, Kathryn A; Whitsett, Jeffrey A; McCormack, Francis X; Xu, Yan; Yu, Jane J (2023. ) Single-cell multiomic analysis identifies a HOX-PBX gene network regulating the survival of lymphangioleiomyomatosis cells.Science advances, , 9 (19 ) ,eadf8549 More Information

Astrinidis, Aristotelis; Li, Chenggang; Zhang, Erik Y; Zhao, Xueheng; Zhao, Shuyang; Guo, Minzhe; Olatoke, Tasnim; Mattam, Ushodaya; Huang, Rong; Zhang, Alan G; Pitstick, Lori; Kopras, Elizabeth J; Gupta, Nishant; Jandarov, Roman; Smith, Eric P; Fugate, Elizabeth; Lindquist, Diana; Markiewski, Maciej M; Karbowniczek, Magdalena; Wikenheiser-Brokamp, Kathryn A; Setchell, Kenneth D R; McCormack, Francis X; Xu, Yan; Yu, Jane J (2023. ) Upregulation of acid ceramidase contributes to tumor progression in tuberous sclerosis complex.JCI insight, , 8 (9 ) , More Information

Lahooti, Behnaz; Akwii, Racheal G; Patel, Dhavalkumar; ShahbaziNia, Siavash; Lamprou, Margarita; Madadi, Mahboubeh; Abbruscato, Thomas J; Astrinidis, Aristotelis; Bickel, Ulrich; Al-Ahmad, Abraham; German, Nadezhda A; Mattheolabakis, George; Mikelis, Constantinos M (2023. ) Endothelial-Specific Targeting of RhoA Signaling via CD31 Antibody-Conjugated Nanoparticles.The Journal of pharmacology and experimental therapeutics, , 385 (1 ) ,35-49 More Information

Book Chapter

Astrinidis, Aristotelis; Henske, Elizabeth Petri (2006 ) Mutation detection in tumor suppressor genes using archival tissue specimens. Methods in molecular medicine .(pp. 185-96).

Texas Tech University Health Sciences Center, School of Pharmacy (Student Enhancement and Retention Committee ) Member Type:University/College Service Level:College 2014 -2015

Texas Tech University Health Sciences Center (Institutional Animal Care and Use Committee (IACUC) ) Member Type:University/College Service Level:University 2015 -2016

Texas Tech University Health Sciences Center, School of Pharmacy (Continuing Education Committee (CEC) ) Member Type:University/College Service Level:College 2015 -2016

Texas Tech University Health Sciences Center, Graduate School of Biomedical Sciences (Bylaws Update Committee ) Member Type:University/College Service Level:College 2015 -2015

Texas Tech University Health Sciences Center, Graduate School of Biomedical Sciences (Biotechnology Program Committee ) Member Type:University/College Service Level:College 2015 -2016

Texas Tech University Health Sciences Center, Graduate School of Biomedical Sciences (Graduate Council ) Member Type:University/College Service Level:College 2015 -2016

Alex’s Lemonade Stand Foundation Reviewer Type:Grant Panel Level:National 2010 -2013

Austrian Research Fund Member Type:Grant Panel Level:International 2005 -2005

Tuberous Sclerosis Association (UK) Reviewer Type:Grant Panel Level:International 2009 -2009

Epilepsy Ireland Reviewer Type:Grant Panel Level:National 2016 -2016

Israel Science Foundation (Israel) Reviewer Type:Grant Panel Level:National 2010 -2011

Israel Science Foundation (Israel) Reviewer Type:Grant Panel Level:National 2021 -2021

The Wellcome Trust (UK) Reviewer Type:Grant Panel Level:National 2011 -2011

Tuberous Sclerosis Alliance (USA) Reviewer Type:Grant Panel Level:National 2013 -2018

Tuberous Sclerosis Alliance (USA) Reviewer Type:Grant Panel Level:National 2020 -2021

Tuberous Sclerosis Association (UK) Reviewer Type:Grant Panel Level:National 2013 -2014

Tuberous Sclerosis Association (UK) Reviewer Type:Grant Panel Level:National 2017 -2017

Vienna Science and Technology Fund-WWTF (Austria) Reviewer Type:Grant Panel Level:National 2011 -2011

World Hellenic Bio-Medical Association Reviewer Type:Service to Professional Development Programs Level:International 2019 -2020

(Ad-hoc publication reviewer ) Reviewer Type:Other Level:International 2006 -2021

1998-2002 Postdoctoral Associate, Fox Chase Cancer Center, , Philadelphia, PA

Academic - 231 Albert Sabin Way
Cincinnati  Ohio, 45267
aristotelis.astreinidis@uc.edu