Dr. Mehdi Hayat Shahi has completed his graduation, post-graduation, and M.Phil. from Aligarh Muslim University, Aligarh. After obtaining the CSIR-JRF qualification, he joined the laboratory of Prof. Subrata Sinha, Department of Biochemistry, AIIMS, New Delhi, as a CSIR-Junior Research Fellow in January 2004 to work on the molecular biology of primary human brain glial tumors. Dr. Shahi joined Aligarh Muslim University in 2005 as a PhD Student under the supervision of Prof. Mohammad Afzal, A.M.U., Aligarh, and co-supervision of Prof. Subrata Sinha, AIIMS, New Delhi. He has done extensive work on glial tumors during this period. This has resulted in several publications in well-established journals in the field. Dr. Shahi has consistently pursued research in molecular neuro-oncology throughout his scientific career, developing a strong foundation in this field. He had continued with his interest in molecular cancer genetics at the University of Uppsala in Sweden. He did his post-doctoral research at the University of California, Davis, USA, on a project related to the Shh pathway in brain tumors.

Interestingly, his published article received a special mention in the News and Prospects section of the Journal of the American Medical Association (JAMA) in 2016. Since June 2015, he has been working as an Assistant Professor at the Interdisciplinary Brain Research Centre (IBRC), Aligarh Muslim University, Aligarh. Dr. Shahi has been awarded the Ramanujan Fellowship from the Department of Science and Technology (DST), Govt. of India, New Delhi. This is a great honor for him, and the award acknowledges his dedicated research in the field of molecular neuro-oncology, which is particularly strong in the theoretical aspects of life sciences and in experimental design and interpretation.

Dr. Shahi's research interest is in Molecular Neuro-oncology. He is investigating the role of the Sonic hedgehog (Shh) cell signalling pathway in the development of brain tumors, including medulloblastoma, glioblastoma, and neuroblastoma. The following are his significant research contributions:

• He is one of the pioneers who identified the role of the Sonic hedgehog cell signaling pathway in the most common brain tumors, glioma and neuroblastoma (Shahi et al., 2008).

• During embryonic development, Shh cell signaling plays a crucial role in neural tube development and this pathway regulates neural tube patterning with the aid of homeodomain transcription factors. Normally, Shh upregulates homeodomain transcription class I Nkx2.2 and downregulates homeodomain transcription factor class II Pax6 in the early embryonic neural tube development. However, Shahi et al. reported that Shh cell signaling, with its main transcription factor Gli1, may upregulate Pax6 and downregulate Nkx2.2 in common brain tumors medulloblastoma and glioblastoma (Shahi et al., 2010). Moreover, this investigation suggests that Pax6 may be considered a potential oncogene, while Nkx2.2 is a potential tumor suppressor gene (Shahi et al., 2010; Shahi et al., 2014).

• Dr. Shahi is also a pioneer in reporting the epigenetic regulation of Hedgehog interacting protein (HHIP) gene methylation in the human brain tumor samples (Shahi et al., 2011b; Shahi et al., 2015).

• Dr. Shahi also reported one of the novel stem cell markers, BMI1 high expression, and drug resistance in glioblastoma. He knocked down the BMI1 gene and demonstrated its interaction with the Shh-Gli1 cell signaling pathway and the drug resistance gene MRP1 (Shahi et al., 2016).

• Dr. Shahi's research group is also a pioneer in reporting the protein-protein docking and molecular dynamics simulation of Gli1 with Pax6 and glioma biomarker gene IDH2. He has reported the differential dynamic interaction of Gli1-IDH2 and Gli1-Pax6. MDS results revealed that the interaction of Gli1 with IDH2 was stronger and more stable than Pax6 (Farheen, Shahi et al., 2022).

• Dr. Shahi's research group is also the first to report the time-dependent regulation of stem cell factors BMI1 and NANOG by miRNA-30-5p in the Shh-mediated pediatric brain tumor medulloblastoma (Ahmed et al., 2024).

• Recently, Dr. Shahi's group demonstrated the differential regulation of homeodomain transcription factors Nkx2.2 and Pax6 in medulloblastoma genesis (Mariyath PM et al., 2024).

• Chemoresistance and recurrences are significant challenges in the treatment of brain tumors. Therefore, Dr. Shahi and his group have screened numerous compounds and molecules to identify the most effective molecules for treating brain tumors. After a rigorous screening approach, they identified one molecule, ARSH, which showed a more effective and efficient effect on glioblastoma cells as compared to the contemporary drug temozolomide. Notably, even a nanomolar concentration of this compound drug is sufficient, compared to a micromolar concentration of TMZ. This significant finding has been approved by the Indian Patent No. 562661 in 2025 (Shahi et al., 2025). This molecule is currently undergoing further validation in a pre-clinical study.

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