About

Professor Ashish Tyagi is associated with the Texas A&M Irma Lerma Rangel College of Pharmacy. The provided page text does not include specific details about his research focus, background, or key contributions. Therefore, no detailed biography information is available from the given content.

Research topics

• Biology
• Cell biology
• Cancer research
• Biochemistry
• Chemistry
• Endocrinology
• Genetics

Selected publications

• Mechanistic role of metal-responsive transcription factor-1 (MTF-1) in cadmium-induced prostate carcinogenesis

  International Journal of Biological Sciences · 2025-05-27 · 3 citations

  articleOpen access

  Our previous report emphasized that chronic exposure to cadmium (10 µM) over one year led to the transformation of benign prostatic hyperplasia (BPH1) cells into malignancy through the ZIC2 signaling pathway (cerebellar zinc pathway). However, the upstream mechanisms that trigger this transformation have yet to be fully elucidated. The present study suggests that cadmium exposure induces metal regulatory element-binding transcription factor-1 (MTF1), which activates ZIC2 in BPH1 cells. Interestingly, knocking out ZIC2 expression did not affect MTF1 levels, indicating that MTF1 acts upstream of the ZIC2 signaling pathway. To further investigate the MTF-1/ZIC2 relationship, we overexpressed MTF-1 in untransformed BPH1 cells leading to the induction of ZIC2 along with other stem cell markers, such as ALDH1A1, Nanog, and CD44. This overexpression also facilitated spheroid formation. Conversely, silencing MTF1 expression in transformed cells inhibited spheroid formation and also reduced survival rate. It diminished the expression of stem cell and epithelial-to-mesenchymal transition markers and tumor growth in nude mice. Transcriptomic analysis of MTF1 silenced xenograft tumors confirmed these findings. Using CRISPR-Cas9 to knock out ZIC2 also prevented tumor formation in nude mice. These results emphasize the critical role of MTF1 in the oncogenic process and its involvement in the ZIC2-mediated transformation associated with Cd-induced malignant changes.

  PublisherOA PDFDOI

• Urolithins: Emerging natural compound targeting castration-resistant prostate cancer (CRPC)

  Biomedicine & Pharmacotherapy · 2025-04-19 · 1 citations

  reviewOpen accessSenior author

  Castration-resistant prostate cancer (CRPC) presents a significant challenge due to its resistance to conventional androgen deprivation therapies. Urolithins, bioactive metabolites derived from ellagitannins, have recently emerged as promising therapeutic agents for CRPC. Urolithins not only inhibit androgen receptor (AR) signaling, a crucial factor in the progression of CRPC, but also play a key role in regulating oxidative stress by their antioxidant properties, thereby inhibiting increased reactive oxygen species, a common feature of the aggressive nature of CRPC. Research has shown that urolithins induce apoptosis and diminish pro-survival signaling, leading to tumor inhibition. This review delves into the intricate mechanisms through which urolithins exert their therapeutic effects, focusing on both AR-dependent and AR-independent pathways. It also explores the exciting potential of combining urolithins with androgen ablation therapy, opening new avenues for CRPC treatment.

  PublisherDOI

• Clinical and Echocardiography Outcomes Following Pericardiectomy in Chronic Constrictive Pericarditis

  Journal of the Practice of Cardiovascular Sciences · 2025-01-01 · 1 citations

  articleOpen access

  Abstract Export Introduction: The leading cause of chronic constrictive pericarditis differs according to geographic location. Tuberculosis remains the most common cause of constrictive pericarditis in Africa and Asia, whereas in western countries, it remains a rare entity and idiopathic causes remain the most common etiology. Here, our aim was to study the clinical and echocardiography outcomes postpericardiectomy and compare it with other previous clinical studies. Materials and Methods: This is a retrospective study of 12 months with a mean follow-up period of 2.40 ± 2.01 years. PHILIPS EPIQ 7C machine was used for echocardiographic analysis. Mitral and tricuspid inflow velocities were detected using pulsed-wave Doppler in apical four-chamber view with a sample volume of 2–4 mm. Results: All the patients in the study population presented with dyspnea 19 (100%). Annulus reversus was observed in all our patients (19, 100%), which resolved completely postoperatively. The mean duration of hospital stay was 26.63 ± 13.09 days with a mean intensive care unit stay of 5.89 ± 2.4 days. Discussion: CVP decreased from a mean of 31.9±4.89mmHg preoperatively to 12.95 ± 3.84 mmHg in the immediate postoperative period. Significant reduction (P < 0.001) was noted in inspiratory mitral E velocity without significant change in expiratory mitral E velocity. Significant respirophasic variation was noted in all patients’ mitral and tricuspid E velocity (P < 0.001). Discussion: Different from international studies, we observed pericarditis in younger age group with a mean age of 26.58 ± 11.9 years which could be accountable to tuberculosis in young generation in India, as also observed by other Indian studies. In our study, there was significant respirophasic variation in the mitral and tricuspid E velocity in all patients (P < 0.001). Conclusions: Studies on detailed echocardiographic evaluation in terms of various parameters like mitral and tricuspid E velocities and tissue Doppler imaging are sparse. This study adds to the important role of echocardiography in assessment of chronic constrictive pericarditis.

  PublisherDOI

• Interaction between NF-κB and PLAC8 impairs autophagy providing a survival advantage to prostate cells transformed by cadmium

  Science Advances · 2025-06-13 · 4 citations

  articleOpen accessCorresponding

  Prostate cancer risk is influenced by various factors, including exposure to heavy metals like cadmium (Cd). The study reveals that the autophagy-regulating gene PLAC8 (placenta-specific 8) is significantly involved in Cd-induced prostate carcinogenesis, and NF-κB acts as the upstream transcriptional activator of PLAC8, which then selectively up-regulates BCL-xL, providing a survival advantage to Cd-transformed cells. NF-κB activation stabilizes PLAC8 in the cytosol, disrupting autophagy by allowing PLAC8 to colocalize with LC3B instead of LAMP1. Silencing NF-κB down-regulates PLAC8 and its survival function while inhibiting NF-κB or PLAC8, which restores autophagy and decreases tumor growth in xenograft models. In addition, targeting BCL-xL confirmed this signaling pathway. The findings suggest that sustained NF-κB activation regulates PLAC8 and highlights the NF-κB-PLAC8-BCL-xL axis as a potential target for early detection and therapies in metal-induced prostate cancer.

  PublisherDOI

• Methods to Detect Epigenetic Changes

  2025-01-01

  book-chapterSenior author
  PublisherDOI

• Corrigendum: A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth

  Frontiers in Pharmacology · 2024-05-27 · 1 citations

  erratumOpen access

  [This corrects the article DOI: 10.3389/fphar.2023.1150774.].

  PublisherOA PDFDOI

• Effectiveness of Command-and-Control in Mitigating Industrial Pollution: Evidence from Environmental Regulation in India

  SSRN Electronic Journal · 2024-01-01

  articleOpen access1st authorCorresponding
  PublisherDOI

• Abstract LB027: Identifying natural inhibitors of androgen receptor (AR) and its variants from NCI Natural Product Repository

  Cancer Research · 2024-04-05

  article

  Abstract Second-generation androgen ablation therapies (ADT), enzalutamide, and abiraterone are initially effective on metastatic castration-resistant prostate cancer (mCRPC). However, nearly 30-40% of patients eventually become resistant to these treatments due to the presence of androgen-receptor variants (AR-V), which lack a ligand-binding domain. The grim reality that metastatic CRPC is virtually incurable for most patients poses a significant challenge for clinicians striving to enhance these individuals' quality of life and lifespan. Considering drug discovery efforts, we partnered with the National Cancer Institute's (NCI) Natural Product Repository, which possesses a diverse collection of natural product extracts derived from plant, marine, and microbial organisms. We developed high-throughput phenotypic screening assays to screen the crude natural product extract libraries on AR and AR-variants CRPC cell lines (C4-2B and 22Rv1). Several extracts inhibited the growth of both CRPC cell lines and were further confirmed for dose-dependent cell viability inhibition assays. Once we determined the IC50 dose, we performed a Western blot analysis that confirmed the inhibition of AR and AR-V7 expression in CRPC cells.In subsequent studies, we narrowed down by fractionating the most potent extracts and confirmed their ability to inhibit AR expression and signaling on CRPC cell lines. Currently, we are characterizing the potent compounds and their inhibitory activity on AR and AR-variants, in vitro and in vivo CRPC models. Many nutraceuticals have been shown to target AR signaling, synthesis, or degradation which effectively inhibited the growth of CRPC. Our collaborative efforts with NCI will permit us find N-terminal AR degrading molecules (AF-1), which are essential for the AR transcriptional activities of CRPC. In sum, discovery of ovel small molecules from our drug development program have the potential to translate these effective natural products into drugs with clinical benefits to treat CRPC. Citation Format: Neha Tyagi, Sepideh Hosseiniporgham, Ashish Tyagi, Balaji Chandrasekaran, Katherine Bonilla, Inna Kriger, James Saccchettini, Chendil Damodaran. Identifying natural inhibitors of androgen receptor (AR) and its variants from NCI Natural Product Repository [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB027.

  PublisherDOI

• Abstract 2105: Targeting the “Achilles Heel” of androgen receptor activity in castration resistant prostate cancer

  Cancer Research · 2024-03-22

  article1st authorCorresponding

  Abstract Background: Each year, millions of men are diagnosed with prostate cancer (CaP). The unchecked activation of the Androgen Receptor (AR) spurs CaP development and progression. Mutations or the presence of AR splice variants can add complexity to tumor ecology, leading to chemoresistance. This study aims to develop novel inhibitors targeting the “Achilles Heel” of AR activity: the N-terminal domain (NTD). This would circumvent the limitations of LBD (Ligand Binding Domain) therapies and offer a superior treatment option for patients. Though the AR-NTD is an intrinsically disordered protein, which complicates structure-based drug design, we have developed a unique small molecule inhibitor, ASR600, which specifically targets AR-NTD and promotes AR and AR- variants degradation by ubiquitination at previously unknown sites. Methods: Mass-spec analysis was performed to identify distinct ubiquitination sites in AR's NTD. To perform spatial transcriptome analysis, CytAssist Visium (10X genomics) was used. Furthermore, we used western blotting, immunofluorescence, immunoprecipitation, and PDX mice studies in CRPC mouse models to examine the impact of ASR600 on CRPC. Results: Four AR ubiquitination sites: K845, K847, and K913 (LBD) and K311 (NTD) are already identified. Interestingly, ASR600 continued to inhibit AR expression even with mutated ubiquitination sites. Mass spectrometry analysis of ASR-mediated mono-ubiquitinated N-terminal AR identified K16 as a unique ubiquitin acceptor. Altering this ubiquitination site rescues AR expression from ASR600-mediated degradation, emphasizing AR N-terminus as an ASR600 target. To discern the role of the K16 ubiquitination site in AR protein turnover, we evaluated AR protein stability in LNCaP cells that stably expressed ARWT or AR-K16R constructs. Our data indicates the pivotal importance of K16 for AR transcriptional activity. Invivo, ASR600, when used as a sole agent, exhibited inhibitory responses in PDX of clinically aggressive, AR-expressing tumors. Spatial gene expression analysis revealed marked expression differences in AR signature genes between control and ASR600-treated PDX tissues. Crucially, AR signaling, and related markers mainly aligned with epithelial markers rather than stromal ones. In contrast, the ASR600-treated PDX tumor showcased reduced AR signaling within epithelial cells. Conclusion: Targeting AR-NTD has received a lot of attention, but its innately disordered structure has hindered progress. ASR600 targets AR-NTD specifically by ubiquitinating the protein at a novel location, K16. Our in vivo, PDX studies, combined with the spatial analysis, lay a strong foundation for initiating IND-enabling TOX studies, followed by a phase-I clinical trial for ASR-600 in CRPC patients. Citation Format: Ashish Tyagi, Balaji Chandrasekaran, Arun K. Sharma, Chendil Damoadaran. Targeting the “Achilles Heel” of androgen receptor activity in castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2105.

  PublisherDOI

• Clinical And Echocardiography Outcomes Following Pericardiectomy In Chronic Constrictive Pericarditis

  IOSR Journal of Dental and Medical Sciences · 2024-12-01

  articleOpen access

  Introduction: Leading cause of chronic constrictive pericarditis differs according to geographic location, tuberculosis remains the most common cause of constrictive pericarditis in Africa and Asia where as in western country it remains a rare entity and idiopathic causes remains the most common etiology. Here our aim was to study the clinical and echocardiography outcomes post pericardiectomy &amp; compare it with other previous clinical studies. Methods: This is a retrospective study of 12 months with mean follow up period of 2.40 ± 2.01 years. PHILIPS EPIQ7C machine was used for echocardiographic analysis. Mitral and tricuspid inflow velocities were detected using PW doppler in apical 4-chamber view with sample volume of 2-4 mm. Results: All the patients in the study population presented with dyspnea 19(100%). Annulus reversus was observed in all our patients (19, 100%), which resolved completely postoperatively. Mean duration of hospital stay was 26.63 ± 13.09 days with mean ICU stay of 5.89 ± 2.4 days. Discussion: Different from international studies, we observed pericarditis in younger age group with mean age of 26.58 ± 11.9 years which could be accountable to Tuberculosis in young generation in India, as also observed by other indian studies. In our study, there was significant respiro-phasic variation in the mitral and tricuspid E velocity in all patients. Conclusions: Studies on detailed echocardiographic evaluation in terms of various parameters like mitral and tricuspid E velocities and tissue doppler imaging are sparce. This study adds to the important role of echocardiography in assessment of chronic constrictive pericarditis.

  PublisherDOI

Frequent coauthors

• Chendil Damodaran

  Texas A&M University

  52 shared

• Balaji Chandrasekaran

  Saveetha University

  45 shared

• Murali K. Ankem

  37 shared

• Arun Sharma

  Pennsylvania State University

  26 shared

• Venkatesh Kolluru

  University of Louisville

  25 shared

• Uttara Saran

  14 shared

• Becca V. Baby

  13 shared

• Srinivasa R. Ramisetti

  11 shared

Education

• Ph.D. Biotechnology, Molecular Biology Unit

  National Dairy Research Institiute and Hemwati Nandan Bahuguna Garhwal University

  2014

• M.Sc. Biotechnology

  Chaudhary Charan Singh University

  2005

• Bachelor of Science

  University of Delhi

  2003

Awards & honors

• Presidential Impact Fellow