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Photo of Aristotelis Astreinidis

Aristotelis Astreinidis

Research Scientist

Internal Medicine | College of Medicine

Education/Credentials
  • B.S.: Aristotle University of Thessaloniki
  • Ph.D.: Aristotle University of Thessaloniki
Contact Information
Research Interests

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

Summary

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.

Peer Reviewed Publications

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

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

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,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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