Jyotirindra Maity, Ph.D., received his Bachelor of Science in Botany with honors from Ramakrishna Mission Vivekananda Centenary College, under Calcutta University in India. During his master's program, he completed two months of summer training at the CSIR Institute of Genomics and Integrative Biology (IGIB) in Delhi, India. He earned his Master of Science in Molecular Biology and Biotechnology from the University of Kalyani, India, in 2010. Dr. Maity obtained his Ph.D. in Cellular and Molecular Biology from the Life Science and Biotechnology department at Jadavpur University, India in 2017, where he studied the DNA damage repair protein WRN and autophagy.
In June 2018, Dr. Maity became a research associate in the Vascular Biology and Stem Cell Research Laboratory in the department of Pharmaceutical Sciences at Texas Tech University Health Sciences Center, Amarillo. His research focused on dental pulp stem cells (DPSC) and autophagy.
Dr. Maity joined the NCI in 2020 as a visiting postdoctoral fellow, working on translational research in ovarian cancer. Subsequently, he joined the NIAMS as a visiting postdoctoral fellow and works on translational bone tumor research related to melorheostosis disease.
Dr. Jyoitirindra Maity has focused on cellular and molecular biology in rare disease models and cancer and stem cell modeling throughout his career. His graduate thesis focused on the nuclear protein Werner (WRN) and autophagy.
WRN is a 1432 amino acid protein consisting of several domains. It has many functions, including replication, transcription, and DNA damage repair. Mutations in WRN lead to premature aging, known as Werner syndrome (WS).
Autophagy is a cytoplasmic conserved catabolic phenomenon to maintain cellular homeostasis. Defects in autophagy cause many serious pathological issues, like aging. Using various cell lines, including normal and WRN mutant fibroblast lines, Dr. Maity's previous research showed that WRN mutant cells respond weakly to different stress-induced autophagy in addition to basal levels. WRN critically regulates autophagy in various cellular stresses, including starvation, endoplasmic reticulum (ER) stress conditions to rescue the cell, and basal situations to restore proper cellular function. Further, he recorded that among several domains, the acidic domain is the most essential for the induction of autophagy.
During his postdoc, he carried out research to determine the role of Kruppel-like factor 2 (KLF2) during osteoblast (OB) differentiation of dental pulp-derived stem cells (DPSC). By applying classical OB differentiation methods and a phytoestrogen ferutinin stimulated OB differentiation procedure, Dr. Maity showed that the levels of KLF2 and autophagy-related molecules increase during osteoblast differentiation. During the cellular differentiation process, cellular metabolism alters as the cell prepares for ongoing changes. It reduces total and mitochondrial ROS generation and induces intracellular Ca2+ production. Simultaneous measurements of glycolysis and oxidative phosphorylation in live cells revealed that OB differentiation decreased the oxygen consumption rate, which indicates reduced ATP production and mitochondrial respiration. Therefore, a metabolic shift from mitochondrial respiration to the glycolytic pathway occurs during OB differentiation. However, each differentiation method has a different impact on cellular metabolic changes. Further Chromatin immunoprecipitation (ChIP) analysis confirmed that the KLF2 and active epigenetic marks (H3K27Ac and H3K4me3) were upregulated in the promoter region ATG7 during OB differentiation. These results provide evidence that the involvement of mitophagy is crucial during OB differentiation, and KLF2 critically regulates it.
In his NCI postdoc, Dr. Maity worked on ovarian cancer. Approximately 40% of high-grade serous ovarian cancer (HGSOC) has defects in homologous recombination (HR) DNA double-strand break (DSB) repair (e.g., BRCA mutations), leading to sensitivity to PARP inhibitor (PARPi). PARPi resistance is common and developed by multiple mechanisms, indicating an unmet need for new treatment strategies. Targeting ATR/CHK1 cell cycle checkpoint is a new approach in the post-PARPi era. However, we have observed restricted clinical activity of CHK1 inhibitor (CHK1i) in PARPi-resistant HGSOC patients, suggesting the possibility of cross-resistance between the two drugs. Dr. Maity worked on a PARPi resistance mechanism that confers the resistance against CHK1i using parental, PARPi-resistant, and CHK1i-resistant BRCA-mutated HGSOC cell lines. Given that DNA helicases are critical for chromosome stability and HR repair, Dr. Maity studied the involvement of DNA helicases in developing cross-resistance of PARPi and CHK1i.
Currently, Dr. Maity works on melorheostosis, a benign tumor on the surface of bones. Previous research from Dr. Bhattacharyya's group determined that mutations in MAP2K1 and SMAD3 are mainly responsible for this disease. Dr. Maity hopes that new treatment strategies may be possible by identifying the illness's inheritance mechanisms.