Projectos Activos:

• Agencia: Italfarmaco
• Titulo del projecto: Characterization of phenotypic changes in myeloid cells in the context of immune deregulation.
• Identificador: ITF0023
• Fecha: 12/01/25-11/30/27
• Rol: Investigador responsable
• Tipo de projecto: SRA

• Agencia: National Institutes of Health
• Titulo del projecto: Development of selective HDAC6 inhibitors to improve cancer immunotherapy.
• Identificador: 1R01CA249248-01A1
• Fecha: 02/01/21-01/31/26
• Rol: Investigador responsable
• Tipo de projecto: R01

• Agencia: Cancer Research Institute
• Titulo del projecto: Macrophage phenotype as a biomarker to predict the effectiveness of Immune Checkpoint Blockade in melanoma patients
• Identificador: 228514
• Fecha: 08/01/22-07/30/26
• Rol: Investigador responsable
• Tipo de projecto: CLIP

Projectos Pasados:

• Agencia: Avstera Therapeutics
• Titulo del projecto: Evaluation of Avstera HDAC6 inhibitors as adjuvants for immunotherapy and macrophage cell therapy
• Identificador: 232018
• Fecha: 11/01/22-10/30/25
• Rol: Investigador responsable
• Tipo de projecto: SRA

• Agencia: Shuttle Pharmaceuticals
• Titulo del projecto: Evaluation of SP-225 HDACi as an adjuvant for radiation therapy
• Identificador: 260997
• Fecha: 02/01/23-10/30/25
• Rol: Investigador responsable
• Tipo de projecto: SRA

• Agencia: National Science Foundation
• Titulo del projecto: EFRI CEE: Human cardiac opto-epigenetics with HDAC inhibitors
• Identificador: NSF 1830941
• Fecha: 08/01/18-07/30/23 (NCE)
• Rol: Multi-PI (Emilia Entcheva, Alejandro Villagra, Shu Jia, Zhenyu Li, Ralph Mazitschek)
• Tipo de projecto: NSF

• Agencia: GWU – McCormick Foundation
• Titulo del projecto: Use of selective HDACi to change the macrophage phenotype
• Fecha: 10/01/19-10/09/20
• Rol: Investigador responsable
• Tipo de projecto: Interno

• Agencia: George Washington University, Office of the Vice President for Research
• Titulo del projecto: Reversing immune evasion in ovarian cancer through nanoparticle-directed epigenetic modulation
• Fecha: 07/01/18-06/30/20
• Rol: Investigador responsable
• Tipo de projecto: Interno

• Agencia: Melanoma Research Foundation
• Titulo del projecto: Use of Selective HDACi to improve antibody blockade immunotherapy.
• Fecha: 01/03/16-12/31/19
• Rol: Investigador responsable
• Tipo de projecto: Fundacion

• Agencia: National Institutes of Health
• Titulo del projecto: An Engineered Nanoimmunotherapy for Melanoma
• Identificador: 1R41CA217294
• Fecha: 04/02/18-03/31/19
• Rol: Investigador responsable
• Tipo de projecto: R41

• Agencia: National Institutes of Health
• Titulo del projecto: Augmenting the immunogenicit6y of melanoma through manipulation of histone deacetylases (HDAC’s)
• Identificador: P50 CAS 168536-01A
• Fecha: 05/01/2013 – 04/30/2018
• Rol: Investigador responsable
• Tipo de projecto: P50

• Agencia: National Institutes of Health
• Titulo del projecto: Role of HDAC6 in the modulation of Immune-related pathways in Melanoma
• Identificador: 1R21 CA184612-01
• Fecha: 04/01/2014 – 05/31/2017
• Rol: Investigador responsable
• Tipo de projecto: R21

• Agencia: Melanoma Research Foundation
• Titulo del projecto: Role of HDAC6 in the modulation of Immune-related pathways in Melanoma
• Identificador: Interno
• Fecha: 10/2013-09/2015
• Rol: Investigador responsable
• Tipo de projecto: Foundation

• Agencia: National Institutes of Health
• Titulo del projecto: Role of Histone Deacetylases 6 and 11 in regulation of IL-10 and immune responses
• Identificador: 1R21CA153246-01A1
• Fecha: 03/2010 – 02/2013
• Rol: Investigador responsable
• Tipo de projecto: R21

• Agencia: Forma Therapeutics
• Titulo del projecto: Participation of selective HDAC6, 8 and 11 inhibitors in the modulation of immune-related pathways
• Fecha: 09/2014 – 08/2016
• Rol: Investigador responsable
• Tipo de projecto: SRA

• Agencia: Forma Therapeutics
• Titulo del projecto: Role of dual and multiple selective HDAC inhibitors in the immunogenicity of cancer and immune cells.
• Fecha: 09/2014 – 08/2016
• Rol: Investigador responsable
• Tipo de projecto: SRA

• Agencia: Acetylon
• Titulo del projecto: Targeting HDAC6 in Melanoma with Isotype-selective HDAC6 inhibitors
• Fecha: 03/2014 – 02/2015
• Rol: Investigador responsable
• Tipo de projecto: SRA

• Agencia: Moffitt Cancer Center – Comprehensive Melanoma Research Center
• Titulo del projecto: Targeting HDACs as a strategy to augment anti-tumor immune responses in Melanoma
• Fecha: 10/2011 — 09/2015
• Rol: Investigador responsable
• Tipo de projecto: Interno

A.- Publicaciones Peer-reviewed:

1. Villagra A, Gutierrez J, Paredes R, Sierra J, Puchi M, Imschenetzky M, Wijnen Av A, Lian J, Stein G, Stein J, Montecino M. (2002). Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts. J Cell Biochem. 2002;85(1):112-22.
2. Sierra J, Villagra A, Paredes R, Cruzat F, Gutierrez S, Javed A, Arriagada G, Olate J, Imschenetzky M, Van Wijnen AJ, Lian JB, Stein GS, Stein JL, Montecino M. (2003). Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity. Mol Cell Biol. 2003 May;23(9):3339-51.
3. Paredes R, Arriagada G, Cruzat F. Villagra A, Olate J, Zaidi K, van Wijnen A, Lian J, Stein G, Stein J, Montecino M. (2003). Bone-Specific Transcription Factor Runx2 Interacts with the 1{alpha},25-Dihydroxyvitamin D3 Receptor to Up-Regulate Rat Osteocalcin Gene Expression in Osteoblastic Cells. Mol Cell Biol. 2004 Oct;24(20):8847-8861.
4. Lee, H., Sengupta, N., Villagra, A., Rezai-Zadeh, N. and Seto, E. (2006) HDAC8 safeguards the human Ever Shorter Telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation. Mol. Cell. Biol. Jul, 26 (14): 5259-69.
5. Villagra A, Cruzat F, Carvallo L, Gutierrez S, Olate J, van Wijnen A, Lian J, Stein G, Stein J, Imbalzano A, Montecino M. (2006). Chromatin Remodeling and Transcriptional Activation of the Bone-specific Osteocalcin Gene requires SWI/SNF Activity. J. Biol. Chem., 281(32):22695-706.
6. Khanna P, Villagra A, Kim S, Seto E, Jaroszeski M, Kumar A, and Bhansali S. (2006) Use of nanocrystalline diamond for microfluidic lab-on-a-chip. Diamond and related materials, 15:2073-2077.
7. Vicente-Suarez I, Brayer J, Villagra A, Cheng F, Sotomayor EM. (2008). TLR5 ligation by flagellin converts tolerogenic dendritic cells into activating antigen-presenting cells that preferentially induce T-helper 1 responses. Immunol Lett. 125(2):114-8.
8. Villagra A, Cheng F, Wang, H, Suarez I, Glozak M, Maurin M, Nguyen D, Wright K, Atadja AP, Bhalla K, Pinilla-Ibarz J, Seto E, Sotomayor E (2009)**. A novel role of histone deacetylase 11 (HDAC11) as transcriptional regulator of IL-10 and Immune tolerance. Nature Immunology, 10:92-100.
9. Cruzat F, Henriquez B, Villagra A, Hepp M, Lian JB, van Wijnen AJ, Stein JL, Imbalzano AN, Stein GS, Montecino MA. (2009). SWI/SNF-Independent nuclease hypersensitivity and increased histone acetylation at the P1 promoter accompany active transcription of the bone master gene RUNX2. Biochemistry. 48(30):7287-95.
10. Villagra A, Ulloa N, Zhang X, Yuan Z, Sotomayor E, and Seto E. (2007). Histone Deacetylase 3 Down-regulates Cholesterol Synthesis through Repression of Lanosterol Synthase Gene Expression. J. Biol. Chem., 282(49):35457-470.
11. Yarde DN, Oliveira V, Mathews L, Wang X, Villagra A, Boulware D, Shain KH, Hazlehurst LA, Alsina M, Chen DT, Beg AA, Dalton WS. (2009). Targeting the Fanconi anemia/BRCA pathway circumvents drug resistance in multiple myeloma. Cancer Res. 69(24):9367-75.
12. Dubovsky JA, Villagra A, Powers JJ, Wang HW, Pinilla-Ibarz J, Sotomayor EM. (2010). Circumventing immune tolerance through epigenetic modification. Curr Pharm Des. 16(3):268-76.
13. Yuan Z, Villagra A, Peng L, Coppola D, Sotomayor E, Chen J, Lane W, Seto E. (2010). The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions. Mol. Cell. Biol. 30:3004-15.
14. Wang H, Cheng F, Woan K, Vicente-Suarez I, Pinilla-Ibarz J, Wright K, Seto E, Bhalla K, Villagra A, Sotomayor E. (2011). Histone deacetylase inhibitor LAQ824 augments inflammatory responses in antigen presenting cells and overcomes T-Cell tolerance through transcriptional regulation of IL-10. J. of Immunology. 186(7):3986-96.
15. Bai F, Villagra A, Zou JX, Painter J, Connolly K, Blaskovich M, Sokol L, Sebti S, Djeu J, Loughran T, Wei S, Sotomayor E, Epling-Burnette PK. (2012). Tipifarnib-mediated suppression of T-bet dependent signaling pathways. Cancer Immunology Immunotherapy. 61(4):523-33.
16. Cheng F, Wang H, Horna P, Wang Z, Shah B, Sahakian E, Woan K, Villagra A, Pinilla-Ibarz J, Sebti S, Smith M, Tao J and Sotomayor E. (2012). Stat3 inhibition augments the immunogenicity of malignant B-Cells leading to effective anti-tumor immunity in B-Cell Lymphomas. Cancer Research. 72(17):4440-8.
17. Bergman J, Woan K, Perez-Villarroel P, Villagra A, Sotomayor E and Kozikowski A. (2012). Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. Journal of Medicinal Chemistry. 55(22):9891-9.
18. Youn J, Kumar V, Collazo M, Nefedova Y, Condamine T, Cheng P, Villagra A, Antonia S, McCaffrey J, Sarnaik A, Sotomayor E and Gabrielovich D. (2013). Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nature Immunology. 14(3):211-20.
19. Woods, D.M., Woan, K., Cheng, F., Wang, H., Perez-Villarroel, P., Lee, C., Lienlaf, M., Atadja, P., Seto, E., Weber, J., Sotomayor, E.M. & Villagra, A*. The anti-melanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by durect tumor cytotoxicity and increased tumor immunogenicity. Melanoma Research. 2013 Oct;23(5):341-8.
20. Kizuka Y, Kitazume S, Okahara K, Villagra A, Sotomayor EM, Taniguchi N. Epigenetic regulation of a brain-specific glycosyltransferase N-acetylglucosaminyltransferase-IX (GnT-IX) by specific chromatin modifiers. J. Biol. Chem. 2014 Apr 18;289(16):11253-61
21. Fengdong Cheng, Maritza Lienlaf, Patricio Perez-Villarroel, Hong-Wei Wang, Calvin Lee, Karrune Woan, David Woods, Tessa Knox, Joel Bergman, Javier Pinilla-Ibarz, Alan Kozikowski, Edward Seto, Eduardo M. Sotomayor and Alejandro Villagra*. Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells. Molecular Immunology. 2014. 2014 Jul;60(1):44-53
22. Cheng F, Wang H, Woan K, Rock-Klotz J, Pinilla-Ibarz J, Seto E, Bhalla K, Kozikowski A, Sotomayor E, Villagra A.** (2013). A novel role for histone deacetylase 6 (HDAC6) in the regulation of the tolerogenic STAT3/IL-10 pathway in antigen presenting cells. J. of Immunology. 2014 Sep 15;193(6):2850-62.
23. Sahakian E, Powers J, Chen J, Deng S, Cheng F, Distler A, Woods D, Rock-Klotz J, Laino A, Youn J, Woan K, Villagra A, Gabrilovich D, Sotomayor E, Pinilla-Ibarz J. Histone deacetylase 11: A novel epigenetic regulator of myeloid derived suppressor cell expansion and function. . Molecular Immunology. (2014) epub ahead.
24. Gonzalez-Zuñiga M., Contreras P., Estrada L., Chamorro D., Villagra A., Zanlungo S., Seto E., Alvarez A. Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer Disease. Molecular Cell. Mol Cell. 2014 Oct 2;56(1):163-73.
25. Paraiso KH, Thakur MD, Fang B, Koomen JM, Fedorenko IV, John JK, Tsao H, Flaherty KT, Sondak VK, Messina JL, Pasquale EB, Villagra A. Rao UN, Kirkwood JM, Meier F, Sloot S, Gibney GT, Stuart D, Tawbi H, Smalley KS. (2015). Ligand-Independent EPHA2 Signaling Drives the Adoption of a Targeted Therapy-Mediated Metastatic Melanoma Phenotype. Cancer Discovery, 2015 Mar;5(3):264-73.
26. Woan K.V., Lienlaf M., Perez-Villaroel P., Lee C., Cheng F., Knox, T., Woods D.M., Barrios, K., Wang H.W., Canales, J., Marante, D., Sarnaik, A., Smalley, K., Bergman J., Kozikowski A., Celis E., Weber J., Sotomayor E.M., and Villagra A* (2015). Targeting Histone Deacetylase 6 (HDAC6) mediates a dual anti-melanoma effect, enhanced anti-tumor immunity and impaired proliferation. Mol Oncol. 2015 Aug;9(7):1447-57
27. David M. Woods, Andressa L. Sodré, Alejandro Villagra, Eduardo M. Sotomayor, Jeffrey Weber (2015). HDAC Inhibition Upregulates PD­1 Ligands in Melanoma and Augments Immunotherapy with PD­1 Blockade. Cancer Immunol Res. 2015 Aug 21.
28. Jie Chen, Eva Sahakian, John Powers, Maritza Lienlaf, Patricio Perez-Villarroel, Tessa Knox, and Alejandro Villagra*. Functional Analysis of Histone Deacetylase 11. Methods Mol Biol. 2016; 1436:147-65
29. John Powers, Jie Chen, Maritza Lienlaf, Patricio Perez-Villarroel, Tessa Knox, Alejandro Villagra, and Eva Sahakian. Expression and Function of Histone Deacetylase 10 (HDAC10) in B Cell Malignancies. Methods Mol Biol. 2016; 1436:129-45
30. Lienlaf M, Perez-Villarroel P, Knox T, Woan K.V., Lee C., Cheng F., Sahakian E., Powers J., Deng S., Smalley K. S. M., Kozikowski A., Pinilla-Ibarz J., Sarnaik, A., Seto E., Weber J., Sotomayor E.M., and Villagra A.* (2016). Essential role of HDAC6 in the regulation of PD-L1 in melanoma. Mol Oncol. 2016 May;10(5):735-50.
31. Villagra A, Sahakian E, Seto E. Preparation and Biochemical Analysis of Classical Histone Deacetylases. Methods Enzymol. 2016; 573:161-81
32. Chen J, Sahakian E, Powers J, Lienlaf M, Perez-Villarroel P, Knox T, Villagra A*. Functional Analysis of Histone Deacetylase 11 (HDAC11). Methods Mol Biol. 2016; 1436:147-65
33. Powers J, Lienlaf M, Perez-Villarroel P, Deng S, Knox T, Villagra A, Sahakian E. Expression and Function of Histone Deacetylase 10 (HDAC10) in B Cell Malignancies. Methods Mol Biol. 2016; 1436:129-45
34. Eva Sahakian, Jie Chen, John Powers, Xianghong Chen, Kamira Maharaj, Susan Deng, Maritza Lienlaf, Hong Wei Wang, Andressa Sodre’, Allison Distler, Limin Xing, Patricio Perez-Villarroel, Sheng Wei, Alejandro Villagra, Ed Seto, Eduardo Sotomayor, Pedro Horna, and Javier Pinilla-Ibarz.. Essential regulatory role for histone deacetylase 11 (HDAC11) in neutrophil function. (2017). J. of Leukocyte Biology Aug;102(2):475-486
35. Sepulveda H, Villagra A, and Montecino M. Tet-mediated DNA demethylation is required for SWI/SNF-dependent chromatin remodeling and histone modifying activities that trigger expression of the Sp7 osteoblast master gene during mesenchymal lineage commitment. (2017) Mol. Cell. Biol. Sep 26;37(20)
36. David M. Woods*, Karrune V. Woan*, Fengdong Cheng, Andressa L. Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, and Eduardo M. Sotomayor. T-cells Lacking Histone Deacetylase 11 Have Increased Effector Functions and Mediate Enhanced Alloreactivity in a Murine Model. (2017) Blood. 2017 Jul 13;130(2):146-155
37. Tavares MT, Shen S, Knox T, Hadley M, Kutil Z, Bařinka C, Villagra A**, Kozikowski AP. Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models. ACS Med Chem Lett. 2017 Sep 5;8(10):1031-1036
38. Perez L, Fernandez H, Horna P, Riches M, Locke F, Field T, Powers J, Sahakian E, Villagra A, Mishra A, Betts B, Kharfan-Dabaja M, Beato F, Ochoa-Bayona L, Pidala J, Anasetti C. (2018). Phase I trial of histone deacetylase inhibitor panobinostat in addition to glucocorticoids for primary therapy of acute graft-versus-host disease. Bone Marrow Transplant. 2018 Apr 18.
39. Maharaj K, Powers JJ, Achille A, Deng S, Fonseca R, Pabon-Saldana M, Quayle SN, Jones SS, Villagra A, Sotomayor EM, Sahakian E, Pinilla-Ibarz J. Silencing of HDAC6 as a therapeutic target in chronic lymphocytic leukemia. Blood Adv. 2018 Nov 13;2 (21):3012-3024.
40. Tessa Knox, Eva Sahakian, Debarati Banik, Melissa Hadley, Erica Palmer, Jennifer Kim, Satish Noonepalle, John Powers, Maria Gracia-Hernandez, Vasco Oliveira, Fengdong Cheng, Jie Chen, Cyril Barinka, Javier Pinilla-Ibarz, Eduardo Sotomayor, Norman H. Lee, Alan Kozikowski, and Alejandro Villagra* (2019). Selective HDAC6 inhibitors as priming agents to improve anti-PD-1 immune checkpoint blockade therapy. Scientific Reports (2019) 16;9(1):6136
41. Hadley M, Noonepalle S, Banik D, Villagra A.* (2019). Functional Analysis of HDACs in Tumorigenesis. Methods Mol Biol. 2019; 1983:279-307. doi: 10.1007/978-1-4939-9434-2_17
42. Shen S, Hadley M, Ustinova K, Pavlíček J, Knox T, Noonepalle S, Tavares M, Zimprich C, Zhang G, Robers M, Barinka C, Kozikowski A, and Villagra A*. Discovery of a New Isoxazole-3-hydroxamate Based Histone Deacetylase 6 Inhibitor SS-208 with Anti-tumor Activity in Syngeneic Melanoma Mouse Models. (2019) Journal of Medicinal Chemistry. Sep 26;62(18):8557-8577. doi: 10.1021/acs.jmedchem.9b00946.
43. Ledezma DK, Balakrishnan PB, Cano-Mejia J, Sweeney EE, Hadley M, Bollard CM, Villagra A, Fernandes R. Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma. (2020) Nanomaterials (Basel). 2020 Jan 17;10(1). pii: E161. doi: 10.3390/nano10010161.
44. Sara Moufarrij, Aneil Srivastava, Stephanie Gomez, Melissa Hadley, Erica Palmer, Paul Austin, Sarah Chisholm, Kyle Roche, Angela Yu, Jing Li, W Zhu, Micael Lopez-Acevedo, Alejandro Villagra**, and Katherine Chiappinelli. Combining DNMT and HDAC6 inhibitors increases anti-tumor immune signaling and decreases tumor burden in ovarian cancer. (2020) Scientific Reports. 2020 Feb 26;10(1):3470. doi: 10.1038/s41598-020-60409-4.
45. Juliana Cano-Mejia, Anshi Shukla, Debbie K. Ledezma, Erica Palmer, Alejandro Villagra, and Rohan Fernandes. CpG-coated Prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma. Transl Oncol. 2020 Oct;13(10):100823. doi: 10.1016/j.tranon.2020.100823. Epub 2020 Jul 8. PubMed PMID: 32652470; PubMed Central PMCID: PMC7348061.
46. Debarati Banik, Satish Noonepalle, Melissa Hadley, Erica Palmer, Maria Gracia-Hernandez, Christian Zevallos-Delgado, Namratta Manhas, Hayk Simonyan, Colin Young, Anastas Popratiloff, Katherine B. Chiappinelli, Rohan Fernandes, Eduardo M. Sotomayor, and Alejandro Villagra*. HDAC6 plays a non-canonical role in the regulation of anti-tumor immune responses, dissemination, and invasiveness of breast cancer. Cancer Res. 2020 Sep 1;80(17):3649-3662. doi: 10.1158/0008-5472.CAN-19-3738. Epub 2020 Jun 30. PubMed PMID: 32605998.
47. Noonepalle, Satish; Shen, Sida; Ptacek, Jakub; Tavares, Maurício; Zhang, GuiPing; Stransky, Jan; Pavlicek, Jiri; Ferreira, Glaucio; Hadley, Melissa; Pelaez, Guido; Bařinka, Cyril; Kozikowski, Alan; Villagra, Alejandro*. Rational Design of Suprastat, a Novel Selective Histone Deacetylase 6 Inhibitor with the Ability to Potentiate Immunotherapy in Melanoma Models. J Med Chem. 2020 Sep 2;. doi: 10.1021/acs.jmedchem.0c00567. [Epub ahead of print] PubMed PMID: 32815366.
48. Reyes SJ, González KB, Rodríguez C, Navarrete-Muñoz C, Salazar AP, Villagra A, Caglevic C, Hepp MI. Cancer immunotherapy: an update. Rev Med Chil. 2020 Jul;148(7):970-982
49. Lin J, Elkon J, Ricart B, Palmer E, Zevallos-Delgado C, Noonepalle S, Burgess B, Siegel R, Ma Y, Villagra A. Phase I Study of Entinostat in Combination with Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. Oncologist. 2021 Aug 24. doi: 10.1002/onco.13957.
50. Preethi Bala Balakrishnan, Debbie K Ledezma, Juliana Cano-Mejia, Jaclyn Andricovich, Erica Palmer, Vishal A Patel, Patricia S Latham, Eric S Yvon, Alejandro Villagra, Rohan Fernandes, Elizabeth E Sweeney. CD137 agonist potentiates the abscopal efficacy of nanoparticle-based photothermal therapy for melanoma (2021). Nano Res. 2022 Mar;15(3):2300-2314. doi: 10.1007/s12274-021-3813-1. Epub 2021 Oct 12.
51. Stephanie Gomez, Olivia L. Cox, Reddick R. Walker III, Uzma Rentia, Melissa Hadley, Elisa Arthofer, Noor Diab, Erin E. Grundy, Tomas Kanholm, James I. McDonald, Julie Kobyra, Erica Palmer, Satish Noonepalle, Alejandro Villagra, David Leitenberg, Catherine M. Bollard, Yogen Saunthararajah, Katherine B. Chiappinelli. Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer. (2022). J Immunother Cancer. 2022 Nov;10(11):e004974. doi: 10.1136/jitc-2022-004974.
52. Amrita Cheema, Yaoxiang Li, Sean Collins, Simeng Suy, Mary Ventimiglia, Keith Kowalczyk, Ryan Hankins, John Lynch, Einsley Janowski, Scott Grindrod, Alejandro Villagra, Anatoly Dritschilo. Radiation therapy induces innate immune responses in patients treated for prostate cancers. (2023). Clin Cancer Res. 2023 Mar 1;29(5):921-929. doi: 10.1158/1078-0432.CCR-22-2340. PMID: 36508164
53. Satish Noonepalle, Scott Grindrod, Nima Aghdam, Xintang Li, Maria Gracia-Hernandez, Christian Zevallos-Delgado, Mira Jung, Alejandro Villagra*, Anatoly Dritschilo. Radiation therapy-induced immune response enhanced by selective HDAC6 Inhibition. (2023) Mol Cancer Ther. 2023 Aug 17:MCT-23-0215. doi: 10.1158/1535-7163.MCT-23-0215.
54. Mardones C, Navarrete-Munoz C, Armijo ME, Salgado K, Rivas F, Gonzalez-Pecchi V, Farkas C, Villagra A & Hepp MI. Role of HDAC6-STAT3 in immunomodulatory pathways in Colorectal cancer cells. (2023) Mol Immunol. 2023 Dec;164:98-111. doi: 10.1016/j.molimm.2023.11.007. Epub 2023 Nov 21. PMID: 37992541.
55. Maria Gracia-Hernandez, Ashutosh Yende, Nithya Gajendran, Zubaydah Alahmadi, Xintang Li, Zuleima Munoz, Karen Tan, Satish Noonepalle, Maho Shibata, Alejandro Villagra. Targeting HDAC6 improves anti-CD47 immunotherapy. (2024). J Exp Clin Cancer Res. 2024 Feb 27;43(1):60. doi: 10.1186/s13046-024-02982-4.
56. Gracia-Hernandez M, Suresh M, Villagra A. The advances in targeting CD47/SIRPα “do not eat me” axis and their ongoing challenges as an anticancer therapy. Oncotarget. 2024 Jul 10;15:462-465. doi: 10.18632/oncotarget.28607.
57. Satish kumar Noonepalle, Maria Gracia-Hernandez, Christian Zevallos-Delgado, Nima Aghdam, Michael Berrigan, Hawa Coulibaly, Xintang Li, Andrew Pletcher, Erica Palmer, Tessa Knox, Eduardo Sotomayor, Katherine B. Chiappinelli, Duncan Wardrop, Anelia Horvath, Brett A. Shook, Norman Lee, Anatoly Dritschilo, Rohan Fernandes, Karthik Musunuri, Maho Shibata, and Alejandro Villagra. (2024) Improving Macrophage Cell Therapy by Reprogramming Macrophages with HDAC6 inhibitors. J Exp Clin Cancer Res. 2024 Sep 14;43(1):263. doi: 10.1186/s13046-024-03182-w.
58. Damian Kovalovsky, Satish Noonepalle, Manasa Suresh, Dileep Kumar, Michael Berrigan, Nithya Gajendran, Sumit Upadhyay, Anelia Horvath, Allen Kim, David Quiceno-Torres, Karthik Musunuri, Alejandro Villagra.The HDAC6-specific inhibitor AVS100 (SS208) blocks M2 polarization of tumor associated macrophages and potentiates immunotherapy in preclinical tumor models. Science Advances. 2024 Nov 15;10(46):eadp3687. doi: 10.1126/sciadv.adp3687. Epub 2024 Nov 15.
59. Gargi Das, Jakub Ptacek, Jana Campbell, Xintang Li, Barbora Havlinova, Satish Noonepalle, Alejandro Villagra, Cyril Barinka, and Zora Novakova. Targeting prostate cancer by new bispecific monocyte engager directed to prostate-specific membrane antigen. (2025). PLoS One. 2025 Mar 17;20(3):e0307353. doi: 10.1371/journal.pone.0307353. eCollection 2025. PMID: 40096254
60. Olaoye, Olasunkanmi ; Erdogan, Fettah; Gracia-Hernandez, Maria; Garcha, Harsimran; Sedighi, Abootaleb; Qirat, Ashraf; Nawar, Nabanita; Geletu, Mulu; Seo, Hyuk-Soo; Abdallah, Diaaeldin ; Abdeldayem, Ayah; Hassan, Muhammad Murtaza; Dhepaganon, Sirano; de Araujo, Elvin; Villagra, Alejandro; Gunning, Patrick. Improved Pharmacokinetic Profiles of HDAC6 Inhibitors Via Cap Group Modification. (2025). J Med Chem. 2025 Sep 11;68(17):18216-18229. doi: 10.1021/acs.jmedchem.5c00479. Epub 2025 Aug 27. PMID: 40864867.
61. Nithya Gajendran, Manasa Suresh, Sebastian J. Marquez Rodriguez, Sruthi Mohan, David Quiceno-Torres, Mario A. Noboa, Bryan Weselman, Xintang Li, Marie Durr, Zora Novakova, Mike Schutkowski, Matias I Hepp, Satish Noonepalle, Cyril Barinka, Duncan Wardrop, and Alejandro Villagra. Macrophage-centric phenotypic screening identifies HDAC6 inhibitors that reprogram the tumor immune microenvironment and improve immune checkpoint blockade. (2026) Journal of Medicinal Chemistry (In press)

B.- Reviews

1. Villagra A, Sotomayor EM, Seto E. (2010). Histone deacetylases and the immunological network: implications in cancer and inflammation. Oncogene, 14;29(2):157-73.
2. Woan KV, Sahakian E, Sotomayor EM, Seto E, Villagra A*. (2012). Modulation of antigen-presenting cells by HDAC inhibitors: implications in autoimmunity and cancer. Immunol Cell Biol. 2012 Jan; 90(1):55-65.
3. Sara Moufarrij 1,2,3,4, Monica Dandapani 1,2,4, Elisa Arthofer 1,4, Stephanie Gomez 1,4, Aneil Srivastava 1,4, Micael Lopez-Acevedo 2,4, Alejandro Villagra 3,4, Katherine B. Chiappinelli 1,4,*. (2018). Epigenetic Therapy for Ovarian Cancer: Promise and Progress. Clinical Epigenetics. 2019 Jan 15;11(1):7
4. Debarati Banik, Sara Moufarrij, and Alejandro Villagra* (2019). Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy. Int J Mol Sci. 2019 May 7;20(9). pii: E2241. doi: 10.3390/ijms20092241
5. Maria Gracia-Hernandez, Eduardo M Sotomayor, Alejandro Villagra*. Targeting macrophages as a therapeutic option in COVID-19. Frontiers in Pharmacology (2020) Oct 29;11:577571
6. M. Gracia-Hernandez, Z. Munoz, A. Villagra. Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers. (2021) Cancers 13 (24), 6180.
7. L Karabon, KB Chiappinelli, A Villagra. Genetic and Epigenetic Control of Immune Responses. (2021) Frontiers in Immunology, 05 October 2021.

C.- Libros

1. Suarez, I. Villagra, A. and Sotomayor, E.M. Signaling pathways in antigen-presenting cells involved in the induction of T-cell tolerance. In: Tumor-induced Immune Suppression: Mechanisms and Therapeutic Reversal. Gabrielovich and Hurwitz, Editors. Springer, New York, NY. Pp197-218, 2008.
2. Sahakian, E., Woan, K., Villagra, A., and Sotomayor, E.M. “Epigenetic Approaches: Emerging role of Histone Deacetylase Inhibitors in Cancer Immunotherapy”. In: Cancer Immunotherapy. Pendergrast, and Jaffe, E. Editors. 2012
3. Woods, DM., Lienlaf-Moreno, M., Sotomayor, EM., Seto, E., Villagra, A. Regulation of the Jak/STATs Pathways by Histone Deacetylases Nuclear Signaling Pathways and Targeting Transcription in Cancer.” Springer Sciences. New York. 2014.
4. Banik, D., Chiappinelli, K. and Villagra, A. Chapter 3 – DNA Methylation and Histone Modifications in Autoimmunity. In: The Epigenetics of Autoimmunity. Elsevier, 2018, Pages 57–86.
5. Melissa Hadley, Satish Noonepalle, Debarati Banik, and Alejandro Villagra. Chapter 17 – Functional Analysis of HDACs in Tumorigenesis. In: Protein Acetylation: Methods and Protocols, Methods in Molecular Biology, vol. 1983. Springer-Nature 2019.

D.- Patentes publicadas

• HISTONE DEACETYLASE 6 INHIBITORS
  Inventors: Wardrop, Duncan (UIC, Chicago), VILLAGRA; Alejandro (Washington, DC)
  Appl. No.: 63/940,978
  Filed: 12/15/2025
• HDAC6 INHIBITORS WITH IMMUNOMODULATORY PROPERTIES
  Inventors: Wardrop, Duncan (UIC, Chicago), VILLAGRA; Alejandro (Washington, DC)
  Appl. No.: 63/711,961
  Filed: 10/25/2024
• COMPOSITIONS FOR AND METHODS OF TREATING A SUBJECT HAVING INFLAMMATION
  Inventors: SHOOK; Brett (Washington, DC), VILLAGRA; Alejandro (Washington, DC), NOONEPALLE; Satish Kumar R. (Washington, DC), HERNANDEZ; Maria (Washington, DC)
  Appl. No.: 18/774580
  Filed: July 16, 2024
• ISOXAZOLE HYDROXAMIC ACIDS AS HISTONE DEACETYLASE 6 INHIBITORS
  Inventors: VILLAGRA; Alejandro (Falls Church, VA), KOZIKOWSKI; Alan P. (Chicago, IL), SHEN; Sida (Chicago, IL)
  Appl. No.: 18/618511
  Filed: March 27, 2024
• STAT-ACTIVATED MACROPHAGES, COMPOSITIONS, AND USES THEREOF
  Inventors: VILLAGRA; Alejandro (Falls Church, VA), NOONEPALLE; Satish (McLean, VA), HERNANDEZ; Maria del Mar Gracia (Reston, VA)
  Appl. No.: 18/251060
  Filed: October 29, 2021
• COMPOSITIONS FOR AND METHODS OF TREATING CANCER
  Inventors: Villagra; Alejandro (Washington, DC), Hernandez; Maria del Mar Gracia (Washington, DC)
  Appl. No.: 18/297565
  Filed: April 07, 2023
• SELECTIVE HISTONE DEACETYLASE 6 INHIBITORS
  Inventors: SHEN; Sida (Chicago, IL), VILLAGRA; Alejandro (Falls Church, VA), KOZIKOWSKI; Alan (Chicago, IL)
  Appl. No.: 18/002952
  Filed: June 25, 2021
• HDAC6-ACTIVATED MACROPHAGES, COMPOSITIONS, AND USES THEREOF
  Inventors: VILLAGRA; Alejandro (Falls Church, VA), AGHDAM; Nima (Alexandria, VA), NOONEPALLE; Satish (Falls Church, VA)
  Appl. No.: 17/623050
  Filed: June 26, 2020
• HISTONE DEACETYLASE AS A MODULATOR OF PDLI EXPRESSION AND ACTIVITY
  Inventors: Villagra; Alejandro V. (Tampa, FL), Sotomayor; Eduardo M. (Tampa, FL)
  Appl. No.: 17/685892
  Filed: March 03, 2022
• HISTONE DEACETYLASE 6 INHIBITION FOR ENHANCING T-CELL FUNCTION DURING ANTI-TUMOR RESPONSE AND TUMOR-PEPTIDE VACCINATION
  Inventors: Sotomayor; Eduardo M. (Tampa, FL), Villagra; Alejandro V. (Tampa, FL)
  Appl. No.: 17/176243
  Filed: February 16, 2021
• Selective histone deactylase 6 inhibitors
  Inventors: Sotomayor; Eduardo M. (Tampa, FL), Bergman; Joel A. (Chicago, IL), Kozikowski; Alan P. (Chicago, IL), Villagra; Alejandro V. (Tampa, FL), Woan; Karrune V. (Gainesville, FL)
  Appl. No.: 15/695435
  Filed: September 05, 2017

Pregrado

• Ciencias Básicas Aplicadas, Medicina

Postgrado

• Biomedicina Celular y Molecular, MCB
• Aspectos Inmunológicos en Cáncer, MCB
• Proyecto de Tesis I, MCB
• Tesis I, MCB
• Tesis II, MCB

• Inmunoterapia y epigenética en cáncer
• Cambios en el sistema inmune durante el envejecimiento
• Evaluacion de cambios ene l sistema myeloide en enfermedads cronicas
• Caracterizacion fenotípica de macrófagos
• Diseno y evaluación de nuevas drogas para modificar el sistema inmune
• Diseno y evaluacion de terapias celulares
• Creacion de sistemas humanizados para el estudio de nuevas terapias

Pregrado

• Molecular Biology II for Biochemistry students
  University of Concepcion, Chile
  Lecturer
  Number of Direct Contact Hours: 6/week
  March 2004 – February 2005
  Number of Students: 50
• Molecular Biology I for Biomedicine students
  University of Concepcion, Chile
  Lecturer
  Number of Direct Contact Hours: 6/week
  March 2004 – February 2005
  Number of Students: 60
• Biochemistry for Veterinary students
  University of Americas, Concepcion, Chile
  Course Director
  Number of Direct Contact Hours: 8/week
  June 2004 – December 2004
  Number of Students: 24
• Undergraduate Research Biology (BISC 4171)
  George Washington University
  Research Supervisor
  Number of Direct Contact Hours: 3/week
  Spring 2016 – Present
  Number of Students: 1-2 per period (total 14)

Postgrado

• Medical Genomics (BIOC6236) (GENO6236)
  George Washington University
  Course Director
  Number of Direct Contact Hours: 2/week
  Fall 2017 – Present
  Number of Students: 14-22
• Molecular Oncology and Epigenetics (CANC 8222)
  George Washington University
  Course Co-Director
  Number of Direct Contact Hours: 4 hours/week
  Spring 2019 – Present
  Number of Students: 4-6
• Biochemical Genetics and Medicine (BIOCHEM 6222)
  George Washington University
  Lecturer
  Number of Direct Contact Hours: 8 (4 lectures)
  Spring 2018 – Present
  Number of Students: 12-20
• Advanced Reading (BIOC 6298)
  George Washington University
  Supervisor
  Number of Direct Contact Hours: 1/week
  Spring 2017 – Present
  Number of Students: 1 per period
• Biological Concepts (PUBH 6001)
  George Washington University
  Invited Lecturer
  Number of Direct Contact Hours: 1/week
  Fall 2017
  Number of Students: 1 per period
• Immunology and Immunotherapy of Cancer (CANC 8223)
  George Washington University
  Lecturer
  Number of Direct Contact Hours: 1 Lecture
  Spring 2020
  Number of Students: 5
• Cancer Epigenetics (TBIO 6523)
  Georgetown
  Lecturer
  Number of Direct Contact Hours: 8 (4 lectures)
  Spring 2017 – Present
  Number of Students: 12-18
• Cellular and Molecular Biomedicine (MCB0201)
  Universidad Catolica de las Santisima Concepcion, Chile
  Lecturer
  Number of Direct Contact Hours: 8 (4 lectures)
  Fall 2021 – Present
  Number of Students: 6-10
• Intro to Tumor Biology (TBIO 6584)
  Georgetown
  Lecturer
  Number of Direct Contact Hours: 1
  Spring 2023 – Present
  Number of Students: 12-18
• Tumor Biology (TBIO 6508)
  Georgetown
  Lecturer
  Number of Direct Contact Hours: 6 (3 lectures)
  Spring 2022 – Present
  Number of Students: 12-18