Miguel Otero, PhD

Dr. Miguel Otero is an Associate Scientist in the Orthopedic Soft Tissue Research Program, Co-Director of the Derfner Foundation Precision Medicine Laboratory, and Co-Director of the HSS Research Institute Histopathology Service at the Hospital for Special Surgery (HSS), and Assistant Professor of Cell and Developmental Biology in Orthopaedic Surgery at Weill Cornell Medical College.

Dr. Otero received his MSc in Biology and his PhD in Molecular Biology from the University of Santiago de Compostela, in Spain. After completing a period of post-doctoral training at the Beth Israel Deaconess Medical Center, Harvard Medical School, he joined HSS as a post-doctoral fellow. He has been a Scientist at HSS since 2006.

Dr. Otero aims to deepen our understanding of the altered signaling pathways that prompt joint tissue disruption in osteoarthritis (OA), with emphasis in developing precision-medicine based approaches to improve patient care. Working in multidisciplinary teams with HSS surgeons, rheumatologists, engineers, pathologists, bioinformaticians, and radiologists, Dr. Otero uses comprehensive state-of-the-art approaches to analyze patient samples and define knee OA patient subtypes, assess how different joint tissues contribute to OA disease, and test non-surgical therapies. His laboratory also uses in vivo preclinical models and cell culture assays to understand disease mechanisms and uncover potential therapeutic targets.

His early research focused in the contribution of abnormal adiposity to rheumatic diseases, with emphasis on assessing the contribution of adipokines and its interacting partners to chondrocyte catabolism and joint destruction. More recently, his research focuses in understanding how altered immune/inflammatory pathways that are abnormally activated in response to injurious biochemical and biochemical stimuli lead to long-lasting (epigenetic) alterations in different joint cells, which in turn drive knee fibrosis and stiffness, and cartilage degradation. Ultimately, Dr. Otero's work aims to improve our understanding of the underlying mechanisms that lead to disease onset and progression, and to develop approaches with potential therapeutic application.

Research

Modulating determinants of joint fibrosis: We are performing comprehensive cellular and molecular analyses in clinical material (joint tissues and whole blood) and in tissues retrieved from preclinical models aiming to better define factors that contribute to joint fibrosis in patients with osteoarthritis (OA), and to identify risk factors with prognostic value in OA patients undergoing total knee arthroplasty. Ultimately, we aim to modulate the levels and activities of these factors to develop targeted preventative therapies.

Assessing the contribution of the infrapatellar fat pad (IPFP) to knee OA: We aim to define cellular and molecular changes in OA IPFPs that have functional impact and contribute to joint fibrosis and the structural progression of knee OA. To do this, we conduct comprehensive histological, immunohistochemical, cellular and molecular characterization of the IPFPs retrieved from OA patients and non-OA controls, paired with in vitro analyses and with work in preclinical models aiming to test therapeutic intervention.

Identification of effective non-surgical therapies for orthopedics: As part of the efforts of the HSS Center for Regenerative Medicine, we use multimodal approaches aiming to identify, characterize, and implement efficacious non-surgical therapies (including platelet-rich-plasma or cell-based approaches) to treat a wide array of orthopedic conditions, from management of established disease (e.g. treatment of knee osteoarthritis) to prevention of long-term damage (e.g. prevent post-traumatic osteoarthritis following ACLR surgery). We combine laboratory studies with clinical trials, and integrate comprehensive analyses of clinical samples with patient outcomes. We aim to gain mechanistic insight on how the composition and biologic activity of these non-surgical therapies impact joint health, and to identify the optimal pairing between the patient-intrinsic characteristics and the treatment modality to optimize treatment efficacy.

Research Interests

Osteoarthritis
Joint fibrosis and inflammation
Orthopedic diseases

Extramural Grant Funding

Anna-Maria and Stephen Kellen Foundation (Role: Co-PI)
Orthopaedic Research and Education Foundation (Role: Co-I)

Departments

Specialized Centers

Precision Medicine Laboratory
HSS Center for Regenerative Medicine
Complex Joint Reconstruction Center

Appointments

Affiliations

Osteoarthritis Research Society International (Member)
Orthopaedic Research Society (Member)

Education

B.S./M.S, School of Biology, University of Santiago de Compostela, Spain
Ph.D., School of Medicine, University of Santiago de Compostela
Postdoctoral, Beth Israel Deaconess Medical Center, Harvard Medical School
Postdoctoral, Hospital for Special Surgery, New York

Awards

2000 - 2004 Pre-doctoral Fellowship from Xunta de Galicia (Spain)
2005 - 2006 Post-doctoral Fellowship from Caixa Galicia Foundation (Spain)
2008 - 2011 Post-doctoral Fellowship from Arthritis Foundation, New York Chapter.
2015 -2017 Nancy Dickerson Whitehead Research Fellowship, HSS
2017- Ira W. DeCamp Fellowship in Musculoskeletal Genetics, HSS

Languages

English, Galician, Spanish

Selected Journal Articles

Kirksey MA, Lessard SG, Khan M, Birch GA, Oliver D, Singh P, Rotundo V, Sideris A, Gonzalez Della Valle A, Parks ML, Sculco PK, Otero M. Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study. Sci Rep. 2022 Jul 25;12(1):12651. doi: 10.1038/s41598-022-16868-y. PubMed PMID: 35879399; PubMed Central PMCID: PMC9314445.

Singh P, Wang M, Mukherjee P, Lessard SG, Pannellini T, Carballo CB, Rodeo SA, Goldring MB, Otero M. Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis. Sci Rep. 2021 Oct 26;11(1):21107. doi: 10.1038/s41598-021-00269-8. PubMed PMID: 34702854; PubMed Central PMCID: PMC8548547.

Zahir H, Dehghani B, Yuan X, Chinenov Y, Kim C, Burge A, Bandhari R, Nemirov D, Fava P, Moley P, Potter H, Nguyen J, Halpern B, Donlin L, Ivashkiv L, Rodeo S, Otero M. In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis. Sci Rep. 2021 Jun 1;11(1):11493. doi: 10.1038/s41598-021-90174-x. PubMed PMID: 34075069; PubMed Central PMCID: PMC8169703.

Singh P, Lessard SG, Mukherjee P, Rourke B, Otero M. Changes in DNA methylation accompany changes in gene expression during chondrocyte hypertrophic differentiation in vitro. Ann N Y Acad Sci. 2021 Apr;1490(1):42-56. doi: 10.1111/nyas.14494. Epub 2020 Sep 25. PubMed PMID: 32978775; PubMed Central PMCID: PMC7990741.

Wang M, Lessard SG, Singh P, Pannellini T, Chen T, Rourke BJ, Chowdhury L, Craveiro V, Sculco PK, van der Meulen MC, Otero M. Knee fibrosis is associated with the development of osteoarthritis in a murine model of tibial compression. J Orthop Res. 2021.

Culley KL, Lessard SG, Green JD, Quinn J, Chang J, Khilnani T, Wondimu EB, Dragomir CL, Marcu KB, Goldring MB, Otero M. Inducible knockout of CHUK/IKKα in adult chondrocytes reduces progression of cartilage degradation in a surgical model of osteoarthritis. Sci Rep. 2019 Jun 20;9(1):8905. doi: 10.1038/s41598-019-45334-5. PubMed PMID: 31222033; PubMed Central PMCID: PMC6586628.

Singh P, Marcu KB, Goldring MB, Otero M. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy. Ann N Y Acad Sci. 2019 Apr;1442(1):17-34. doi: 10.1111/nyas.13930. Epub 2018 Jul 15. Review. PubMed PMID: 30008181.

Otero M, Peng H, Hachem KE, Culley KL, Wondimu EB, Quinn J, Asahara H, Tsuchimochi K, Hashimoto K, Goldring MB. ELF3 modulates type II collagen gene (COL2A1) transcription in chondrocytes by inhibiting SOX9-CBP/p300-driven histone acetyltransferase activity. Connect Tissue Res. 2017 Jan;58(1):15-26. doi: 10.1080/03008207.2016.1200566. Epub 2016 Jun 16. PubMed PMID: 27310669; PubMed Central PMCID: PMC5326708.

Otero M, Plumb DA, Tsuchimochi K, Dragomir CL, Hashimoto K, Peng H, Olivotto E, Bevilacqua M, Tan L, Yang Z, Zhan Y, Oettgen P, Li Y, Marcu KB, Goldring MB. E74-like factor 3 (ELF3) impacts on matrix metalloproteinase 13 (MMP13) transcriptional control in articular chondrocytes under proinflammatory stress. J Biol Chem. 2012 Jan 27;287(5):3559-72. doi: 10.1074/jbc.M111.265744. Epub 2011 Dec 9. PubMed PMID: 22158614; PubMed Central PMCID: PMC3271009.

Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011 Sep;23(5):471-8. doi: 10.1097/BOR.0b013e328349c2b1. Review. PubMed PMID: 21788902; PubMed Central PMCID: PMC3937875.

For more publications, please see the PubMed listing.

Selected Books/Chapters

Culley KL, Singh P, Lessard S, Wang M, Rourke B, Goldring MB, Otero M. Mouse Models of Osteoarthritis: Surgical Model of Post-traumatic Osteoarthritis Induced by Destabilization of the Medial Meniscus. Methods Mol Biol. 2021;2221:223-260. doi: 10.1007/978-1-0716-0989-7_14. PMID: 32979207.

Goldring, M., Culley, K., Wondimu, E., Otero, M. Cartilage and Chondrocytes. Kelley & Firestein's Textbook of Rheumatology, 10th Edition, Chapter 3. 2015; ISBN 978-0-3233-16965.

Otero M, Favero M, Dragomir C, Hachem KE, Hashimoto K, Plumb DA, Goldring MB. Human chondrocyte cultures as models of cartilage-specific gene regulation. Methods Mol Biol. 2012; 806:301-36. doi: 10.1007/978-1-61779-367-7_21. PubMed PMID: 22057461. https://www.ncbi.nlm.nih.gov/pubmed/22057461

Selected Presentations

"Epigenomic Analyses Uncovered Changes in DNA Methylation Accompanying the Progression of Post Traumatic Osteoarthritis Folllowing Destabilization of Medical Meniscus Surgeries, and Lrrc15 as a Potential Contributing Factor to the Dysregulated Phenotype of Osteoarthritis Chondrocytes" 2021, Osteoarthritis Genetics and Epigenetics Webinar, Osteoarthritis Research Society International (Speaker: Dr. Purva Singh)

"Orthobiologics to treat osteoarthritis: can we be more precise?" 2020, WCM-Clinical and Translational Science Center, Research in Progress Series Seminar, New York, NY

"Epigenomic Changes Accompanying the Progression of Surgically Induced Osteoarthritis" 2020, 9th Annual Musculoskeletal Repair and Regeneration Symposium, Albert Einstein College of Medicine, NY

"Changes in DNA methylation contribute to the phenotypic instability of chondrocytes in osteoarthritis." 2019, NYU Center for Skeletal & Craniofacial Biology Symposium, New York

"Changes in DNA Methylation Patterns Are Associated with the Progression of Post-Traumatic Osteoarthritis." 2019, UCONN Health Schools of Medicine & Dental Medicine

"In vitro OA Models to Study Chondrocytes and Cartilage" 2018, World Congress on Osteoarthritis, Liverpool, UK

"Chondrocyte Hypertrophy and Osteoarthritis" 2017, Institute of Endemic Disease, Xi'an Jiaotong University School of Medicine, Xi'an, China

"Precision Medicine for Orthopedics: Understanding Molecular Osteoarthritis." 2016, Keller Army Community Hospital / USMA Research Symposium; West Point Department of Chemistry and Life Science, West Point, New York

"Inflammation and Osteoarthritis" 2015, Xi'an Jiaotong University School of Medicine, Xi'an China

"Mice with a Cartilage-Specific Knockout of the Nuclear Factor Kappa-B Kinase Subunit Alpha (IKKalpha) Are Protected from Cartilage Degradation Following Surgical Induction of Osteoarthritis." 2015, Gordon Research Conference on Cartilage Biology and Pathology, Galveston TX, United States