Silvana Valdebenito-Silva PhD. Assistant Professor

Dr. Valdebenito-SilvaDepartment of Neuroscience
Research Building 17, Room 5.212C 
Route: 1110 | Email: sivaldeb@utmb.edu

 

Lab Website:  cellstocells.com

Education and Training
Universidad de Chile, Santiago, Chile. Bs 2011 (Chemistry) 
Universidad de Chie, Santiago, Chile. Ph.D. 2016 (Chemistry)
Rutgers University, Public Health Research Institute (PHRI), Newark, NJ. (Postdoctoral Training)
The University of Texas Medical Branch, Galveston, TX. (Postdoctoral Training) 
 

Research Interests

My laboratory studies a novel long-range communication system known as Tunneling Nanotubes (TNTs). We have discovered that TNTs are thin, F-actin-based processes that enable direct cytoplasm-to-cytoplasm communication between "sick" and healthy cells, bypassing the extracellular space. These nanotubes facilitate the exchange of intracellular organelles, aggregated proteins, cancer-protective factors, and even viruses, allowing the spread of disease elements across connected cells. 

The laboratory identified that TNTs are not present in healthy conditions, rather, they are induced by pathogens and diseases, including HIV, glioblastoma, and neurodegenerative disorders. Intriguingly, blocking TNT formation dramatically reduces the toxic outputs of these conditions. Our ongoing work seeks to develop novel approaches to modulate TNTs, potentially transforming our understanding of brain pathophysiology and offering new therapeutic strategies for incurable diseases. 

Currently, we are working on:

1. The role of TNTs in Neuro HIV and cure efforts:

As of the end of 2022, approximately 39 million people were living with HIV, a virus that can enter the CNS early in infection, where it persists for the lifespan of the individual. Even with effective antiretroviral therapy (ART), nearly half of people living with HIV experience cognitive impairment. The mechanisms behind this neurodegeneration are not fully understood, but our research points to TNT-mediated amplification of HIV within the CNS. My laboratory identified that TNTs are induced by HIV infection and reactivation. Our central hypothesis is that "Viral reservoirs utilize TNTs to spread infection and induce bystander neuronal and glial damage, even in the era of ART." Through advanced cellular and molecular techniques, we are exploring the mechanisms by which TNTs facilitate HIV transmission in settings with minimal extracellular virus, such as during acute infection or viral reactivation. Blocking TNTs offers a promising therapeutic strategy to hinder viral persistence and aid in HIV cure efforts.

2. TNTs and Cancer Resistance:

A New Frontier in Glioblastoma Research we demonstrated that TNTs are induced in response to cancer treatments, allowing the spread of DNA repair enzymes across tumors, and reducing the effectiveness of therapies. This TNT-based mechanism of bystander protection is especially prominent in glioblastoma (GBM), an aggressive and fatal brain tumor affecting 18,000 Americans annually. Despite advances in treatment, GBM remains largely incurable, with most patients relapsing after treatment. This novel insight suggests that TNTs are key contributors to therapy resistance in GBM, explaining why this tumor type exhibits such high resilience to conventional treatments. By targeting TNTs, we aim to disrupt this communication network and improve therapeutic outcomes for GBM patients.


Selected Publications

  1. Valdebenito S, Ono A, Rong L, Eugenin EA. (2023) The role of tunneling nanotubes during early stages of HIV infection and reactivation: implications in HIV cure. Neuroimmune Pharm Ther. 2(2):169-186. doi: 10.1515/nipt-2022-0015. PMID: 37476291; PMCID: PMC10355284.
  2. Valdebenito S, Malik S, Luu R, Loudig O, Mitchell M, Okafo G, Bhat K, Prideaux B, Eugenin EA. (2021) Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions. Sci Rep. 15;11(1):14556. doi: 10.1038/s41598-021-93775-8. PMID: 34267246; PMCID: PMC8282675.
  3. Valdebenito S, Castellano P, Ajasin D, Eugenin EA. (2021) Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell-to-cell viral transfer. J Neurochem. 158(2):429-443. doi: 10.1111/jnc.15336. PMID: 33655498.
  4. Okafo G, Valdebenito S, Donoso M, Luu R, Ajasin D, Prideaux B, Gorantla S, Eugenin EA. (2020) Role of Tunneling Nanotube-like Structures during the Early Events of HIV Infection: Novel Features of Tissue Compartmentalization and Mechanism of HIV Spread. J Immunol. 15;205(10):2726-2741. doi: 10.4049/jimmunol.2000803. PMID: 33037140; PMCID: PMC8034560.