Subhash Mukhopadhyay Centre for Stem Cell Biology and Regenerative Medicine (SMC-SCBRM)

Our research is focused on various aspects of specification and development of the immortal germline. We study how epigenetic barriers are virtually wiped out upon specification and how the epigenetic landscape is faithfully re-established in every generation towards the acquisition of the totipotent state and eventually for full-term development.

However, there are some loci that retain relics of epigenetic information of the cells from which they are derived. These reminiscent epigenetic information or “escapees” suggest that epigenetic inheritance is an exception rather than a rule. We are also interested to understand how these resistant loci can serve as the candidates of transgenerational epigenetic inheritance and how these escapes can be susceptible to various environmental factors.

Our previous work has demonstrated how epigenetic stress acts a driver of oncogene-induced senescence, which is a major fail-safe mechanism that counteracts tumorigenesis. We are now interested to learn lesson that would be emanated from our work on immortal germline to ameliorate developmental and age-related disorders.

Publications:

1. Muniz L, Deb MK, Aguirrebengoa M, Lazorthes S, Trouche D, Nicolas E. (2017) Control of gene expression in senescence through transcriptional read-through of protein-coding convergent genes. Cell Reports 21; 2433-2446.

2.  Deb S, Felix DA, Koch P, Deb MK, Szafranski K, Buder K, Sannai M,Kirkpatrick J, Pietsch S, Riemenschneider P, Gollowitzer A, Koeberle A,González-Estévez C, Rudolph KL. (2020) Tnfaip2/exoc3-driven lipid metabolism is essential for stem cell differentiation and organ homeostasis. EMBO Reports e49328.

Research interests:

As part of DeBaRUn (Development, Bioengineering & Reproduction Unit) Lab’s research, we seek to understand the male germline development or in simple terms, how fertile sperm cells are born. We emphasize on the questions related to how male gametes develop in fetal gonad, how they remain quiescent during pre-puberty, and how they both self-renew and differentiate to obtain the mature, fertile form in adulthood across diverse patient populations. Answering these questions will provide us with criteria for selecting the epigenetically and physiologically fittest cells for In Vitro Fertilization (IVF) that are tailored to each individual patient. We apply single-cell genomics, microfluidic engineering, biochemical and embryological testing, and machine learning to track germline lineages and develop patient-specific, noninvasive biomarker panels for selecting fertile sperm to improve ART outcomes.

Our core expertise includes:

• Single-cell transcriptomics of spermatogenesis: Profiling stage-specific gene expression and transcriptional regulation (including RNA Polymerase II pausing) during mammalian male germ cell development.
• Germ cell biology & transplantation: Analysis of fetal and adult germline lineage progression and cell population dynamics.
• Sperm guidance & selection mechanisms: Specialized in sperm thermotaxis, the role of opsins (rhodopsin/melanopsin) in thermos-sensory signaling, and the development of microfluidic devices for functional sperm selection.
• Non-coding RNA (ncRNA) biomarker discovery: Investigating the roles of miRNAs, piRNAs, tRNA fragments, and long non-coding RNAs in sperm competence and early embryogenesis.

Selected Publications

1. Roy, D., Levi, K., Kiss, V., Nevo, R., & Eisenbach, M. (2020). Rhodopsin and melanopsin coexist in mammalian sperm cells and activate different signaling pathways for thermotaxis. Scientific Reports, 10(1), 112.
2. Kaye, E.G., …, Roy, D., …, & Reddi, P.P. (2024). RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis. Nature Communications, 15(1), 848.
3. Brandis, A.*, Roy, D.*, Das, I., Mordechai, S., & Eisenbach, M. (2024). Uncommon opsin’s retinal isomer is involved in mammalian sperm thermotaxis. Scientific Reports, 14(1), 10699. (Joint first author)
4. Roy, D., Dey, S., Majumder, G.C., & Bhattacharyya, D. (2015). Role of epididymal anti sticking factor in sperm capacitation. Biochemical and Biophysical Research Communications, 463(4), 948-953.
5. Roy, D., Dey, S., Majumder, G.C. et al. Occurrence of novel Cu²⁺-dependent sialic acid-specific lectin, on the outer surface of mature caprine spermatozoa. Glycoconj J 31, 281–288 (2014).

Recent Presentation

1. “Temporospatial asynchrony in marmoset male germline development.” Cold Spring Harbor Laboratory Conference: Germ Cells, October 2024.

Vision

Our goal is to create a research program with a focus on sperm biology, germline genomics, and clinical embryology that develops diagnostic tools and clinical protocols to enhance the success in Assisted Reproductive Technology (ART) and honor the legacy of Dr. Subhash Mukhopadhyay.

Please contact Dr. Roy directly by email for more information.