Pablo Sanchis

• Doctor of Philosophy
• PostDoc Position at University of Buenos Aires

Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infe...

Background/Objectives: Prostate cancer (PCa) is the leading malignancy and the third most common cause of cancer-related death in Argentinian men. Predicting outcomes in localized PCa remains difficult due to tumor heterogeneity. In this study, we assessed the impact of AR (CAG)n and APEX1 c.444T>G polymorphisms on biochemical relapse in Argentine...

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-sc...

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-sc...

PURPOSE This study probes the role of Heme Oxygenase-1 (HO-1) and its nuclear interactors in prostate cancer (PCa). Previous results, demonstrated the anti-tumoral role of HO-1 in PCa and its nuclear translocation, hinting at its potential regulatory roles within the nucleus. Thus, we postulate that HO-1, alongside its interactors, can reprogram PC...

PURPOSE Prostate cancer (PCa) bone metastasis (BM) plays a crucial role in disease outcome and poses a significant clinical obstacle due to its heterogeneity. In this sense, Osteopontin (SPP1/OPN) is elevated in a subset of patients with advanced disease. However understanding its regulation is an unmet need. In this work we investigated the factor...

PURPOSE Carbon monoxide (CO) is recognized for its anti-inflammatory, anti-apoptotic, and anti-proliferative properties. The application of carbon monoxide-releasing molecules (CO-RMs) is thus a promising strategy for therapeutic interventions in various pathological conditions, particularly in the field of oncology. This study aims to evaluate the...

Pancreatic ductal adenocarcinoma (PDAC) represents a very aggressive type of pancreatic cancer (9% survival rate at 5 years). PDX1 is an important transcription factor for embryonic development of the pancreas, endocrine lineage differentiation and the maintenance of mature beta cells. Notably, in PDAC patients, the expression of PDX1 is downregula...

Prostate cancer (PCa) is the second most diagnosed cancer in men globally, and it is positioned as the fifth leading cause of cancer-related death in males. PCa aggressiveness and mortality is intricately linked to the metastatic disease, which is propelled by PCa stem cells (PCSCs). We have previously showcased the strong antitumoral role heme oxy...

About 88% of metastatic prostate cancer (PCa) cases involve bone metastasis. When PCa cells spread to the bone, a metabolic adaptation to the new environment takes place, partly influenced by factors secreted by the homing organ. Thus, we hypothesize that metabolic reprogramming, both in the tumor and bone niche drive PCa bone metastasis. In this w...

The androgen receptor (AR) serves as a pivotal transcription factor in prostate cancer (PCa) development. Its transcriptional activity is linked to the number of glutamines in the N-terminal domain. While current screening for PCa and prognostic biomarkers include serum prostate-specific antigen (PSA) levels and histopathological characteristics (s...

Previous studies have demonstrated the non-canonical anti-tumor effect of heme-oxygenase 1 (HO-1) in prostate cancer (PCa). Although HO-1 is crucial for free heme degradation, its nuclear expression unveils non-canonical functions beyond its enzymatic function. Understanding the specifics of its non-canonical role remains a critical unmet need. In...

Purpose: Metabolic rewiring is critical for the adaptation of tumor cells to the new homing organ. We sought to identify metabolic dysregulations fueling PCa bone metastasis, modulated by bone secreted factors. Methods: By an indirect co-culture system of PCa (PC3) and bone progenitor cells (MC3T3, pre-osteoblasts, or Raw264.7, pre-osteoclasts), we...

Purpose: Mortality in prostate cancer (PCa) patients is mostly associated with bone metastasis and aggressive phenotypes promoted by prostate cancer stem cells (PCSCs). We have previously described that heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme catabolism with antioxidant and antiinflammatory properties, presents an antitumoral role...

Eighty percent of prostate cancers (PCa) metastasize to bone, showing a significant source of patient morbidity. PCa stem-like cells (PCSCs) are capable to quiescently outlast retaining the ability to proliferate and regenerate, consequently remaining able to develop therapy-resistant tumors and metastatic lesions. We have previously reported that...

SARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive an...

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and-negative patients, we identified IFN-γ-associated pathways to be enriched in pos...

Interferon gamma may be a potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-gamma pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2 positive and negative patients, we identified IFN-gamma-associated pathways to be enriched in p...

Bone hosts the 88% of Prostate Cancer (PCa) metastases and no curative therapy is currently available for this stage. Arrival of PCa cells to the bone homing organ is accompanied by a metabolic adaptation, which may be mediated by bone secreted factors. Herein, we sought to identify key metabolic genes fueling PCa bone metastasis and soluble factor...

PURPOSE Prostate cancer (PCa) is a progressive disease involving multiple molecular alterations. The Gleason Grade (GG) is used as an aid for physicians to evaluate the prognosis of men with PCa using samples from prostate tissues. However, some PCa that are histo-pathologically grouped in the same GGs can differ significantly in outcome. The aim o...

PURPOSE Prostate cancer stem cells enhance the tumor's capacity to proliferate, metastasize, and to resist therapies. Thus, stemness represents a therapeutic challenge in prostate cancer (PCa). We have previously reported a strong anti-tumoral effect of heme oxygenase 1 (HO-1) in prostate carcinogenesis in vivo and in vitro. However, its associatio...

PURPOSE The arrival of metastatic prostate cancer (PCa) tumor cells to the bone niche requires a metabolic adaptation. We sought to identify metabolic dysregulations fueling PCa metastasis, modulated by bone secreted factors. METHODS By an indirect co-culture system of PCa (PC3) and bone progenitors (MC3T3, pre-osteoblasts, or Raw 264.7, pre-osteo...

PURPOSE Prostate cancer (PCa) is the second most common type of cancer in men and the sixth leading cause of cancer-related death in men worldwide. The discovery of new therapeutic avenues in PCa, and the development of effective drugs in the era of personalized medicine, would greatly benefit from the field of proteomics. We have previously shown...

Metastatic prostate cancer (PCa) cells soiling in the bone require a metabolic adaptation. Here, we identified the metabolic genes fueling the seeding of PCa in the bone niche. Using a transwell co-culture system of PCa (PC3) and bone progenitor cells (MC3T3 or Raw264.7), we assessed the transcriptome of PC3 cells modulated by soluble factors relea...

Prostate cancer (PCa) cells display abnormal expression of proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown the anti-tumoral role of heme oxygenase 1 (HO-1) in this disease. In this work, we undertook a mass spectrometry-based proteomics study to identify HO-1 molecular interac...

Heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, is involved in the maintenance of cellular homeostasis, exerting a cytoprotective role by its antioxidative and anti-inflammatory functions. HO-1 and its end products, biliverdin, carbon monoxide and free iron (Fe²⁺), confer cytoprotection against inflammatory and oxidative inju...

Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The underlying mechanisms that account for the ultimate emergence of resistance to ADT, progressing to castrate-resistant prostate cancer (CRPC), include those that reactivate androgen receptor (AR), or those that are entirely independent or cooperate...

Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus-infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton-dependent trafficking controlled by Rho GTPases...

p>Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis. Using PCa patient-derived xenografts (PDXs) we assessed the metabolic changes after castration of tumor-bearing mice. We found th...

p>Cancer is a risk factor for SARS-CoV-2 infection. Recent reports have shown that prostate cancer (PCa) patients undergoing androgen-deprivation therapies (ADT) were partially protected from COVID-19. The human myxovirus resistance gene 1 (MX1) is expressed in many tissues, including prostate, and we have previously demonstrated its antitumoral ac...

Differential gene expression analysis is widely used to study changes in gene expression profiles between two or more groups of samples (e.g., physiological versus pathological conditions, pre-treatment versus post-treatment, and infected versus non-infected tissues). This protocol aims to identify gene expression changes in a pre-selected set of g...

Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme...

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction in PCa. LC ESI–MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues and peptide data was integra...

Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis. Using PCa patient-derived xenografts (PDXs) we assessed the metabolic changes after castration of tumor-bearing mice. We found that...

Stem cells genome safeguarding requires strict oxidative stress control. Heme oxygenase-1 (HO-1) and p53 are relevant components of the cellular defense system. p53 controls cellular response to multiple types of harmful stimulus, including oxidative stress. Otherwise, besides having a protective role, HO-1 is also involved in embryo development an...

In a published case-control study (GSE152075) from SARS-CoV-2-positive (n = 403) and -negative patients (n = 50), we analyzed the response to infection assessing gene expression of host cell receptors and antiviral proteins. The expression analysis associated with reported risk factors for COVID-19 was also assessed. SARS-CoV-2 cases had higher ACE...

The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological signi...

Background: Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metas...

The host cell receptors and associated anti-viral genes mediating SARS-CoV-2 infections are still elusive. Here, we show that COVID-19 patients compared with healthy donors, display discrepancies regarding up-regulation of ACE2 and TMPRSS2. Further, we have screened in these samples key players associated with the antiviral response: MX1, IRF3, HMO...

The adult zebrafish is considered a useful model for studying mechanisms involved in tissue growth and regeneration. We have characterized cytotoxic damage to the retina of adult zebrafish caused by the injection of cobalt chloride (CoCl2) into the vitreous cavity. The CoCl2 concentration we used primarily caused injury to photoreceptors. We observ...