Ricardo Aguiar, M.D., Ph.D.
Professor of Medicine, Biochemistry, Microbiology, and Immunology
Lymphoma Biology
BCR signaling, transcription factor deregulation, and mitochondrial metabolism
Our group focus is on the identification and functional characterization of the genetic abnormalities of hematologic malignancies. We utilize in vitro and in vivo systems, in genome-wide or targeted studies, with the intent of translating these discoveries into clinical initiatives. The principal disease model in our lab is B-cell lymphoma. Active research lines stem from our recently published work and include: 1) The intersection between B-cell receptor signaling and phosphodiesterase 4 (PDE4) as actionable therapeutic targets in mature B cell malignancies; 2) Metabolic imbalance and epigenetic reprogramming in lymphomas; 3) Transcription factor IRF8 and lymphomagenesis.
Related diseases: B cell lymphomas, lymphoid leukemias
Techniques: Genetic modification of cancer cells in vitro using retrovirus and lentivirus, genetic engineering of mouse models, in vivo (mouse) manipulations, multiple signaling assays, genome-wide analysis (DNA, RNA, and protein) of primary human tumors
Publications
Qiu Z, Lin A-P, Jiang S, Elkashef S, Myers J, Sasi B, Cao JZ, Godley LA, Rakheja D, Lyu Y, Zheng S, Shiio Y, Aguiar RCT. MYC regulation of D2HGDH and L2HGDH influences the epigenome and epitranscriptome. CellChem Biol. 2020 Feb 24. [Epub ahead of print] PMID: 32101699
Srikantan S, Deng Y, Cheng Z-M, Luo A, Qin Y, Gao Q, Docor GM, Shannon CE, Fourcaudot M, Li Z, Kasinath BS, Reddick RL, Dong LQ, Abdul-Ghani M, Norton L, Aguiar RCT, Dahia PLM. The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner. Nature Communications, 10:4720, 2019. PMID: 31624249
Cooney JD, Lin AP, Jiang D, Wang L, Suhasini AN, Myers J, Qiu Z, Wölfler A, Sill H, Aguiar RCT. Synergistic Targeting of the Regulatory and Catalytic Subunits of PI3Kδ in Mature B-cell Malignancies. Clin Cancer Res. 24:1103-1113. 2018. PMID: 29246942
Elkashef SM, Lin AP, Myers J, Sill H, Jiang D, Dahia PLM, Aguiar RCT. IDH Mutation, Competitive Inhibition of FTO, and RNA Methylation. Cancer Cell,31: 619-620. 2017.PMID: 28486104
Kelly KR, Mejia A, Suhasini A, Lin AP, Kuhn JG, Karnad A, Weitman S, Aguiar RCT. Safety and pharmacodynamics of the PDE4 inhibitor roflumilast in advanced B cell malignancies. Clin Cancer Res,23: 1186-1192, 2017. PMID: 27542768
Cooney JD & Aguiar RCTPhosphodiesterase 4 inhibitors have wide-ranging activity in B cell malignancies. Blood,128: 2886-2890, 2016. PMID: 27756749
Suhasini A, Wang L, Holder K, Lin AP, Bhatnagar H, Kim S-W, Moritz A, Aguiar RCT.A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma Leukemia,30: 617-626, 2016
Lin A-P, Abbas S, Kim S-W, Ortega M, Bouamar H, Escobedo Y, Varadarajan P, Qin Y, Sudderth J, Schulz E, Deutsch A, Mohan S, Ulz P, Neumeister P, Rakheja D, Gao X, Hinck A, Weintraub S, DeBerardinis R, Sill H, Dahia PLM, Aguiar RCT. D2HGDH regulates α-alpha-ketoglutarate levels and dioxygenases function by modulating IDH2. Nature Communications, 6:7768, 2015 - doi: 10.1038/ncomms8768
Bouamar H, Jiang D, Wang L, Lin AP, Ortega M, Aguiar RCT. MicroRNA-155 control of p53 activity is context dependent and mediated by Aicda and Socs1. Molecular and Cellular Biology, 35:1329-40, 2015
Grants
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| Funding Agency | Veterans Administration 2I01 BX001882 |
| Title |
IRF8 and lymphomagenesis |
| Status | Active |
| Period |
04/2013- 03/2021 |
| Role | Principal Investigator |
| Grant Detail |
$231,076 |
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| Funding Agency |
Cancer Prevention & Research Institute of Texas RP190043 |
| Title |
Mitochondrial metabolism and RNA methylation in cancer |
| Status | Active |
| Period |
03/2019- 08/2022 |
| Role | Principal Investigator |
| Grant Detail |
$285,655 |
| Funding Agency |
Leukemia and Lymphoma Society 6524-17 |
| Title |
Targeting tumor cell & the microenvironment in DLBCL |
| Status | Active |
| Period |
10/2016- 09/2020 |
| Role |
Principal Investigator |
| Grant Detail |
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| Funding Agency |
Cancer Prevention & Research Institute of Texas RP170146 |
| Title |
B cell receptor signaling intersects with angiogenesis in diffuse large B cell lymphoma. |
| Status | Active |
| Period |
12/2016- 11/2020 |
| Role | Principal Investigator |
| Grant Detail |
$285,655 |
| Funding Agency |
NIH-NIEHS R01 ES031522 |
| Title |
Oxidative stress and RNA methylation |
| Status | Active |
| Period |
04/2020- 03/2025 |
| Role | Principal Investigator |
| Grant Detail |
$250,000 |
Education
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| Year | Degree | Discipline | Institution |
| 1998 | Postdoctoral Fellowship | Lymphoma Biology | Harvard Medical School Boston , MA |
| 1996 | Postdoctoral Fellowship | Leukemia Biology | Centre for Adult Leukaemia, Hammersmith Hospital, University of London London , UK |
| 1994 | PhD | Leukemia Biology (Magna Cum Laude) | University of Sao Paulo, School of Medicine Sao Paulo , Brazil |
| 1992 | Clinical Fellowship | Hematology & Oncology | Hospital das Clinicas, School of Medicine, University of Sao Paulo Sao Paulo , Brazil |
| 1990 | Residency | Internal Medicine | Hospital das Clinicas, School of Medicine, University of Sao Paulo Sao Paulo , Brazil |
| 1988 | MD | Medicine | Federal University of Paraiba Paraiba , Brazil |